EMBO Workshop Research Articles

Membrane Potential Dynamics of GABAergic Neurons in the Barrel Cortex of Awake Mice

Event Abstract Back to Event Membrane Potential Dynamics of GABAergic Neurons in the Barrel Cortex of Awake Mice L. Gentet1* and C. Petersen1 1 INSERM UMR 915, Institut du thorax IRT, France Recent studies performed under “blind-patching” conditions have shown that subthreshold electrophysiological properties of layer 2/3 pyramidal neurons in the barrel cortex of awake, behaving mice display prominent state-dependent changes. Here, we extended such studies to the population of neocortical interneurons through two-photon-targeted whole-cell recordings from knock-in mice expressing GFP from the GAD67 gene locus (Tamamaki et al., 2003)(which labels nearly all GABAergic neurons) or GIN mice (Oliva et al., 2000)(in which a small subset of somatostatin-positive inhibitory neurons are GFP-labelled. In the GAD67-GFP knock-in mice, we further subdivided interneurons into two classes based on their intrinsic electrophysiological properties, Fast-Spiking (FS) and Non-Fast-Spiking (NFS). Our results reveal that both FS and NFS neurons display slow subthreshold oscillations during quiet wakefulness similar to and synchronized with those observed in excitatory cells, while their intrinsic firing rates were considerably higher than excitatory neurons. Correlated oscillations between all cell types became de-correlated during periods of free whisking, while firing rates decreased in FS cells and increased in NFS interneurons. Interestingly, whole-cell recordings in GIN mice show that the small subset of GFP-labelled GABAergic interneurons in this mouse appear to behave very differently from the other neuronal populations that we have so far recorded. The GFP-labelled neurons in the GIN mouse are somatostatin-positive Martinotti cells, which in vitro have also been shown to have interesting and unique properties (Silberberg & Markram, 2007; Kapfer et al., 2007; Xu & Callaway, 2009). Our data provide the first information on the membrane potential dynamics of GABAergic neurons in awake mice, which is of critical importance for understanding the functional operation of neocortical microcircuits. Conference: EMBO workshop: Gaba Signalling and Brain Networks , Amsterdam, Netherlands, 30 Jun - 2 Jul, 2010. Presentation Type: Poster Presentation Topic: Posters Citation: Gentet L and Petersen C (2010). Membrane Potential Dynamics of GABAergic Neurons in the Barrel Cortex of Awake Mice. Conference Abstract: EMBO workshop: Gaba Signalling and Brain Networks . doi: 10.3389/conf.fnins.2010.15.00008 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 23 Jun 2010; Published Online: 23 Jun 2010. * Correspondence: L. Gentet, INSERM UMR 915, Institut du thorax IRT, Nantes, France, luc.gentet@inserm.fr Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers L. Gentet C. Petersen Google L. Gentet C. Petersen Google Scholar L. Gentet C. Petersen PubMed L. Gentet C. Petersen Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Role of electrical activity during cortical interneuron development

Event Abstract Back to Event Role of electrical activity during cortical interneuron development F. Alfonsi1* and N. Tekki-Kessaris1 1 WIBR/UCL, Department of Signal Processing, United Kingdom Electrical activity acts in synergy with genetic programs to regulate different aspects of neuronal development such as precursor proliferation, differentiation, and migration, as well as incorporation of neurons into functional circuits. In vitro studies have shown a role for Glutamate and GABA signals during cortical GABAergic interneuron migration. However, the requirement for these mechanisms in vivo is still unclear. In this study we examine the in vivo role of Glutamate signalling via NMDA receptors during cortical interneuron development. We use a conditional deletion approach where we examine either the cell autonomous effect of deleting NMDAR1 (NR1) in immature migrating interneurons, or the cell non-autonomous effect of disrupting NR1 in cortical pyramidal neurons. We find a requirement for NR1-mediated signals in both cortical interneurons as well as cortical pyramidal cells: deleting NR1 in either of these two populations has differential effects on cortical interneurons. Conference: EMBO workshop: Gaba Signalling and Brain Networks , Amsterdam, Netherlands, 30 Jun - 2 Jul, 2010. Presentation Type: Poster Presentation Topic: Posters Citation: Alfonsi F and Tekki-Kessaris N (2010). Role of electrical activity during cortical interneuron development. Conference Abstract: EMBO workshop: Gaba Signalling and Brain Networks . doi: 10.3389/conf.fnins.2010.15.00001 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 22 Jun 2010; Published Online: 22 Jun 2010. * Correspondence: F. Alfonsi, WIBR/UCL, Department of Signal Processing, London, United Kingdom, f.alfonsi@wibr.ucl.ac.uk Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers F. Alfonsi N. Tekki-Kessaris Google F. Alfonsi N. Tekki-Kessaris Google Scholar F. Alfonsi N. Tekki-Kessaris PubMed F. Alfonsi N. Tekki-Kessaris Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

GABAergic interneurons in cortical network operations

Event Abstract Back to Event GABAergic interneurons in cortical network operations Thomas Klausberger1, 2* 1 Center for Brain Research, Med. Uni, Department of Cognitive Neurobiology, Austria 2 Oxford University, MRC Anatomical Neuropharmacology Unit, United Kingdom The distributed temporal activity in neuronal circuits of the prefrontal cortex and hippocampus combines emotional information with episodic and spatial memory to guide decisions on behavioural action. In the hippocampus and medial prefrontal cortex of rodents, single neurons of unknown identity exhibit specific firing patterns during spatial decision-making tasks. The cerebral cortex consists of highly diverse neuronal types with distinct synaptic connectivity, molecular expression profile and contribution to network activity. Cortical neurons can be divided into excitatory pyramidal cells, which use glutamate as a neurotransmitter and give both local and long-range axonal projections, and inhibitory interneurons, which are GABAergic and control the activity and timing of pyramidal cells mainly through local axons. Both types of neuron can be further subdivided on the basis of their distinct axo-dendritic arborisations, subcellular post-synaptic targets, and by their differential expression of signalling molecules, including receptors, ion channels, neuropeptides, transcription factors and Ca2+ binding proteins. In order to explain how neuronal circuits support temporal order leading to higher cognitive functions, it is critical to determine the identity and temporal specificity of neurons. We have recorded identified GABAergic interneurons in the medial prefrontal cortex of anaesthetised rats during network oscillations using the juxtacellular recording and labelling technique and investigated their contribution to the synchronisation of theta oscillations between the hippocampus and medial prefrontal cortex. Furthermore, we recorded the activity of hippocampal and prefrontal interneurons and pyramidal cells with tetrodes in freely-moving rats during the learning and execution of a matching-to-place task on a continuous T maze. Overall, our results indicate that different GABAergic interneurons release GABA at distinct times to different domains of pyramidal cells explaining the need of diverse classes of interneurons. This design of the cerebral cortex is consistent with regulating the input integration of individual pyramidal cells through a dynamic interplay between ion channels and precisely timed synaptic inputs, thereby contributing to the formation of cell assemblies and representations in the hippocampus. Conference: EMBO workshop: Gaba Signalling and Brain Networks , Amsterdam, Netherlands, 30 Jun - 2 Jul, 2010. Presentation Type: Oral Presentation Topic: Talks Citation: Klausberger T (2010). GABAergic interneurons in cortical network operations. Conference Abstract: EMBO workshop: Gaba Signalling and Brain Networks . doi: 10.3389/conf.fnins.2010.15.00043 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 24 Jun 2010; Published Online: 24 Jun 2010. * Correspondence: Thomas Klausberger, Center for Brain Research, Med. Uni, Department of Cognitive Neurobiology, Vienna, Austria, thomas.klausberger@pharm.ox.ac.uk Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Thomas Klausberger Google Thomas Klausberger Google Scholar Thomas Klausberger PubMed Thomas Klausberger Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

DECREASED DENSITY OF SOMATOSTATIN-CONTAINING INTERNEURONS IN ADULT RAT BRAIN AFTER PERINATAL PHENCYCLIDINE TREATMENT

Event Abstract Back to Event DECREASED DENSITY OF SOMATOSTATIN-CONTAINING INTERNEURONS IN ADULT RAT BRAIN AFTER PERINATAL PHENCYCLIDINE TREATMENT Vladimir Bumbaširevic1, Igor Jakovcevski2, Nataša D. Petronijevic3 and Nevena V. Radonjic3* 1 School of Medicine, University of Belgrade, Institute of Histology and Embryology, Russia 2 Center for Molecular Neurobiology Hamburg, Germany 3 University of Belgrade, Institute of Medical and Clinical Biochemistry,School of Medicine, Russia GABAergic interneurons perform crucial roles in cortical development and function. Different subclasses of GABA cortical neurons can be distinguished by their content of neuropeptides such as somatostatin (SST) positive cells. SST neurons have been reported to be affected in the prefrontal cortex (PFC) of subjects with schizophrenia. Perinatal phencyclidine (PCP) administration to rats has been established as an animal model of schizophrenia. Our previous studies have demonstrated decreased density of parvalbumin- and reelin-positive interneurons in cortex and hippocampus of the rats perinatally treated with PCP. The aim of this study was to determine effect of perinatal PCP treatment on density of SST containing interneurons in adult rat brain in different forebrain regions. Animals were treated on 2nd, 6th, 9th and 12th postnatal (PN) day, with either PCP (10 mg/kg) or vehicle (0.9% saline) subcutaneously. Cell densities were estimated on PN70 using the optical dissector principle on a fluorescence microscope equipped with Neurolucida software. After perinatal PCP administration density of somatostatin containing interneurons was reduced in dentate gyrus (GD) (-50%) and CA3 (-46%) subregions of hippocampus, while there was no significant change in CA1 subregion. In cingulate, motor and retrosplenial cortex there was no significant change in density of these interneurons. These findings indicate that perinatal blockade of NMDA receptor signaling induces a region-specific disruption in development of SST-containing GABA-ergic neurons. This result is especially interesting considering that SST-containing, dendritic targeting neurons appear to be necessary for filtering out distracting stimuli during working memory processing which is impaired in schizophrenia patients. Conference: EMBO workshop: Gaba Signalling and Brain Networks , Amsterdam, Netherlands, 30 Jun - 2 Jul, 2010. Presentation Type: Poster Presentation Topic: Posters Citation: Bumbaširevic V, Jakovcevski I, Petronijevic ND and Radonjic NV (2010). DECREASED DENSITY OF SOMATOSTATIN-CONTAINING INTERNEURONS IN ADULT RAT BRAIN AFTER PERINATAL PHENCYCLIDINE TREATMENT. Conference Abstract: EMBO workshop: Gaba Signalling and Brain Networks . doi: 10.3389/conf.fnins.2010.15.00019 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 24 Jun 2010; Published Online: 24 Jun 2010. * Correspondence: Nevena V Radonjic, University of Belgrade, Institute of Medical and Clinical Biochemistry,School of Medicine, Belgrade, Russia, radonjin@upstate.edu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Vladimir Bumbaširevic Igor Jakovcevski Nataša D Petronijevic Nevena V Radonjic Google Vladimir Bumbaširevic Igor Jakovcevski Nataša D Petronijevic Nevena V Radonjic Google Scholar Vladimir Bumbaširevic Igor Jakovcevski Nataša D Petronijevic Nevena V Radonjic PubMed Vladimir Bumbaširevic Igor Jakovcevski Nataša D Petronijevic Nevena V Radonjic Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Coordinated Regulation of Inhibitory and Excitatory Local Circuits by Experience During Development of Layer 4 Barrel Cortex

Event Abstract Back to Event Coordinated Regulation of Inhibitory and Excitatory Local Circuits by Experience During Development of Layer 4 Barrel Cortex Michael C. Ashby1, Ramesh Chittajallu1 and John T. Isaac1* 1 NINDS, NIH, United States A critical step in the development of primary sensory cortex is maturation of layer 4, which receives a large proportion of ascending thalamic input to neocortex and contains a precise map of the sensory periphery. In rodent barrel cortex, this map is of the facial vibrissae and during the first postnatal week the map is highly sensitive to whisker-driven sensory experience. Neocortical circuits require a close interplay of inhibition and excitation that together produce a transformation of input into appropriate output. In the case of layer 4, the thalamocortical projection is an important input and the excitatory projection neurons, stellate cells, provide the output. We have thus investigated developmental and experience-dependent changes in local inhibitory and excitatory circuits in layer 4 that are driven by thalamic input and assessed effects on stellate cell output. We analyzed inhibitory and excitatory circuits using simultaneous patch-clamp recordings and 2-photon imaging/uncaging of inhibitory interneurons and stellate cells in a thalamocortical slice preparation from mice aged postnatal day 4 – 12, a period when layer 4 is sensitive to sensory experience. We found that feed forward inhibition, driven by thalamic input onto stellate cells, emerges over approximately 2 days at postnatal day (P)8-9 and involves a number of changes in the circuit. Feed forward inhibition when it emerged serves to strongly down regulate stellate cell spiking in response to thalamic input and set dendritic integration. The recruitment of feed forward inhibition requires sensory experience that selectively strengthens the thalamic input onto fast spiking interneurons; other developmental changes in the inhibitory circuit occur independent of whisker experience. Experiments are now currently underway to assess the role of experience in development of feed back inhibition. To investigate development of the recurrent excitatory network in layer 4, we developed a technique using 2-photon glutamate uncaging to map stellate cell to stellate cell connections. In the first postnatal week connectivity was very low (~4 %), but increases threefold over one day at P9, a time that coincides closely with the emergence of feed forward inhibition. Analysis of structural changes in the same cells shows there is a spinogenesis in stellate cells at P9, in which cells progress from having no spines to hundreds of spines in a period of 1 day. Experience drives the threefold increase in functional connectivity, but is not required for the spinogenesis. Current work using 2-photon glutamate uncaging on spines is investigating mechanisms for experience-dependent regulation of spine function. Taken together our analysis of layer 4 circuit development reveals highly coordinated, rapid, experience-dependent changes in inhibitory and excitatory circuits to produce a layer 4 network that can transform input into appropriate output. Conference: EMBO workshop: Gaba Signalling and Brain Networks , Amsterdam, Netherlands, 30 Jun - 2 Jul, 2010. Presentation Type: Oral Presentation Topic: Talks Citation: Ashby MC, Chittajallu R and Isaac JT (2010). Coordinated Regulation of Inhibitory and Excitatory Local Circuits by Experience During Development of Layer 4 Barrel Cortex. Conference Abstract: EMBO workshop: Gaba Signalling and Brain Networks . doi: 10.3389/conf.fnins.2010.15.00041 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 23 Jun 2010; Published Online: 23 Jun 2010. * Correspondence: John T Isaac, NINDS, NIH, Bethesda, United States, jtrisaac@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Michael C Ashby Ramesh Chittajallu John T Isaac Google Michael C Ashby Ramesh Chittajallu John T Isaac Google Scholar Michael C Ashby Ramesh Chittajallu John T Isaac PubMed Michael C Ashby Ramesh Chittajallu John T Isaac Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

A GABAergic fingerprint identifies stress-susceptibility versus resilience in a chronic mild stress rat model of depression

Event Abstract Back to Event A GABAergic fingerprint identifies stress-susceptibility versus resilience in a chronic mild stress rat model of depression M. Holm1*, K. Jensen1, 2, J. Nieto-Gonzalez1, I. Vardya1 and O. Wiborg2 1 Aarhus University, Synaptic Physiology Laboratory, Department of Physiology and Biophysics, Denmark 2 Aarhus University Hospital, Centre for Psychiatric Research, Denmark It is known that GABAergic hippocampal synapses display short-term synaptic plasticity, i.e. an activity-dependent change in neurotransmitter release during repeated activation. Here we tested whether such synaptic plasticity could be correlated with the behavioral readouts in the chronic mild stress model of depression. Adult male rats were exposed to an eight week long chronic mild stress protocol leading to an anhedonic-like behavior. 350 µm thick ventral horizontal brain slices were prepared for electrophysiological recordings. Spontaneous and evoked inhibitory postsynaptic currents (IPSCs) were recorded in dentate gyrus granule cells. In controls, evoked GABAergic IPSCs showed a paired-pulse ratio (PPR) of 0.81 ± 0.05 (n = 24 cells / 6 rats). In contrast, in stress-susceptible rats the evoked GABAergic IPSCs showed a PPR of 1.26 ± 0.1 (n = 22 cells / 6 rats). Stress-resilient rats showed a paired-pulse ratio which was not significantly different from control rats (PPR of 0.78 ± 0.03 (n = 19 cells / 6 rats)). The GABAB receptor antagonist CGP55845 (5 µM) had no effect on the paired-pulse ratio in any of the groups. Postsynaptically, there were no changes in the frequency and decay kinetics of miniature IPSCs. We propose that stress-susceptibility in rats is associated with presynaptic changes, which may be due to alterations in the presynaptic release machinery, including its complex protein and vesicle composition. Notably, this is the first demonstration of an electrophysiological fingerprint clearly distinguishing stress-susceptible from stress-resilient rats in this model, which indicates that stress-susceptibility is linked to a distinct hippocampal synaptopathy. Conference: EMBO workshop: Gaba Signalling and Brain Networks , Amsterdam, Netherlands, 30 Jun - 2 Jul, 2010. Presentation Type: Poster Presentation Topic: Posters Citation: Holm M, Jensen K, Nieto-Gonzalez J, Vardya I and Wiborg O (2010). A GABAergic fingerprint identifies stress-susceptibility versus resilience in a chronic mild stress rat model of depression. Conference Abstract: EMBO workshop: Gaba Signalling and Brain Networks . doi: 10.3389/conf.fnins.2010.15.00010 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 23 Jun 2010; Published Online: 23 Jun 2010. * Correspondence: M. Holm, Aarhus University, Synaptic Physiology Laboratory, Department of Physiology and Biophysics, Aarhus, Denmark, mmh@biomed.au.dk Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers M. Holm K. Jensen J. Nieto-Gonzalez I. Vardya O. Wiborg Google M. Holm K. Jensen J. Nieto-Gonzalez I. Vardya O. Wiborg Google Scholar M. Holm K. Jensen J. Nieto-Gonzalez I. Vardya O. Wiborg PubMed M. Holm K. Jensen J. Nieto-Gonzalez I. Vardya O. Wiborg Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Brain state dependent firing patterns of identified interneurons in the medial prefrontal cortex

Event Abstract Back to Event Brain state dependent firing patterns of identified interneurons in the medial prefrontal cortex K. Hartwich1, 2*, T. Klausberger1, 2 and L. Massi1, 2 1 Anatomical Neuropharmacology Unit, United Kingdom 2 Medical University of Vienna, Center for Brain Research, Austria In the medial prefrontal cortex, distinct types of neuron form intricate circuits and cooperate in time to support complex operations including working memory, attention and decision making. So far we cannot explain how prefrontal activity is synchronised during altering brain state dependent oscillations based on the spatio-temporal interaction of its organisational elements. To understand the contribution of different types of GABAergic interneuron, we recorded single cells in the medial prefrontal cortex and simultaneously the prefrontal and hippocampal local field potentials in anaesthetised rats. Subsequently, the cells were juxtacellularly labelled and we investigated their axo-dendritic arborisations, expression of molecular markers, postsynaptic targets and spiking activity during different oscillatory frequency bands. Using this approach, we have recently shown that parvalbumin and calbindin expressing basket cells contribute to the synchronisation of local pyramidal cell discharge during hippocampal theta and cortical spindle oscillations, suggesting their strong involvement in timing prefrontal activity to varying inputs. In contrast, calbindin expressing and parvalbumin immuno-negative dendritic-targeting cells are not involved in the oscillation-related timing of pyramidal cell firing during either network activity. Here, we investigate the spike timing of other types of identified GABAergic interneurons during various oscillatory frequency bands and discuss how pyramidal cell synchronisation in the medial prefrontal cortex can be explained by the precise spatio-temporal differentiation of the cell-type specific GABAergic inputs. Conference: EMBO workshop: Gaba Signalling and Brain Networks , Amsterdam, Netherlands, 30 Jun - 2 Jul, 2010. Presentation Type: Poster Presentation Topic: Posters Citation: Hartwich K, Klausberger T and Massi L (2010). Brain state dependent firing patterns of identified interneurons in the medial prefrontal cortex. Conference Abstract: EMBO workshop: Gaba Signalling and Brain Networks . doi: 10.3389/conf.fnins.2010.15.00009 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 23 Jun 2010; Published Online: 23 Jun 2010. * Correspondence: K. Hartwich, Anatomical Neuropharmacology Unit, Oxford, United Kingdom, katjahartwich@gmx.de Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers K. Hartwich T. Klausberger L. Massi Google K. Hartwich T. Klausberger L. Massi Google Scholar K. Hartwich T. Klausberger L. Massi PubMed K. Hartwich T. Klausberger L. Massi Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Input dependent population dynamics in a model of the inhibitory spiking network of medium spiny neurons in the striatum.

Event Abstract Back to Event Input dependent population dynamics in a model of the inhibitory spiking network of medium spiny neurons in the striatum. A. Ponzi1* and J. Wickens1 1 OIST, Japan We investigate a model of an inhibitory spiking network of striatal GABAergic medium spiny neurons (MSN) by computer simulation. We show that the network exhibits complex spatial temporal population dynamics produced by the occurrence of episodically firing cell assemblies even when the inputs from the excitatory cortical cells are composed of many independent Poisson spiking processes, providing the excitatory inputs obey certain conditions. We also show that cell assembly dynamics can occur for several different choices of MSN cell model and is thus a network generated property, while details of MSN cell spiking statistics do depend on the cell model. When cell input firing rates are dynamically variable we show the network can display input dependent population dynamics and investigate how this depends on excitatory input parameters and also on inhibitory network parameters such as connectivity. We discuss how our results may relate to striatal cognitive functions in behavioural tasks. Conference: EMBO workshop: Gaba Signalling and Brain Networks , Amsterdam, Netherlands, 30 Jun - 2 Jul, 2010. Presentation Type: Poster Presentation Topic: Posters Citation: Ponzi A and Wickens J (2010). Input dependent population dynamics in a model of the inhibitory spiking network of medium spiny neurons in the striatum.. Conference Abstract: EMBO workshop: Gaba Signalling and Brain Networks . doi: 10.3389/conf.fnins.2010.15.00018 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 24 Jun 2010; Published Online: 24 Jun 2010. * Correspondence: A. Ponzi, OIST, Okinawa, Japan, aponz1@oist.jp Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers A. Ponzi J. Wickens Google A. Ponzi J. Wickens Google Scholar A. Ponzi J. Wickens PubMed A. Ponzi J. Wickens Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Endogenous GABA regulates GABAB receptor conformation and release probability at single hippocampal synapses

Event Abstract Back to Event Endogenous GABA regulates GABAB receptor conformation and release probability at single hippocampal synapses I. Dolev1, T. Laviv1, I. Riven1, P. Slesinger2, I. Slutsky1* and I. Vertkin1 1 Sackler Faculty of Medicine, Tel Aviv University, Department of Physiology and Pharmacology, Israel 2 The Salk Institute for Biological Studies, Peptide Biology Laboratory, United States Presynaptic GABAB receptor (GABABR) heterodimers, consisting of GB1a/GB2 subunits, critically influence synaptic and cognitive functions. Here we explored local GABABR activation by integrating optical tools for monitoring receptor conformation and synaptic vesicle release at individual presynaptic boutons of hippocampal pyramidal neurons. Utilizing fluorescence resonance energy transfer spectroscopy, we detected high inter-synapse heterogeneity of GB1a/GB2 associations that negatively correlated to release probabilities at single synapses. Notably, both reduction and increase in endogenous activation of receptor decreased inter-synapse variability of GB1a/GB2 association. Despite variability along axons, presynaptic GABABR tone was dendrite-specific, primarily impacting synapses at highly innervated proximal branches. Prolong synaptic disuse reduced both the variability and the degree of GB1a/GB2 associations, leading to homeostatic presynaptic up-scaling. Our findings provide direct evidence for GB1a/GB2 conformational changes by basal GABA release and propose a critical role for the heterodimer conformational dynamics in local regulation of release probability at hippocampal synapses. Conference: EMBO workshop: Gaba Signalling and Brain Networks , Amsterdam, Netherlands, 30 Jun - 2 Jul, 2010. Presentation Type: Poster Presentation Topic: Posters Citation: Dolev I, Laviv T, Riven I, Slesinger P, Slutsky I and Vertkin I (2010). Endogenous GABA regulates GABAB receptor conformation and release probability at single hippocampal synapses. Conference Abstract: EMBO workshop: Gaba Signalling and Brain Networks . doi: 10.3389/conf.fnins.2010.15.00023 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 25 Jun 2010; Published Online: 25 Jun 2010. * Correspondence: I. Slutsky, Sackler Faculty of Medicine, Tel Aviv University, Department of Physiology and Pharmacology, Ramat Aviv, Israel, islutsky@post.tau.ac.il Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers I. Dolev T. Laviv I. Riven P. Slesinger I. Slutsky I. Vertkin Google I. Dolev T. Laviv I. Riven P. Slesinger I. Slutsky I. Vertkin Google Scholar I. Dolev T. Laviv I. Riven P. Slesinger I. Slutsky I. Vertkin PubMed I. Dolev T. Laviv I. Riven P. Slesinger I. Slutsky I. Vertkin Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

The Selective requirement of Activity in maturation of specific cortical interneuron populations.

Event Abstract Back to Event The Selective requirement of Activity in maturation of specific cortical interneuron populations. N. DeMarco1*, Fishell G1 and Karayannis T1 1 NYU Langone Medical Center, Smilow Neuroscience Program and the Departments of Cell Biology and Neural Science, United States Recent experimental evidence uncovered the identity of genetic programs that regulate the generation of GABAergic interneuron subtypes. In contrast, the notion that spontaneous neuronal activity may contribute to interneuron differentiation remains unexplored. Caudal ganglionic eminence (CGE)-derived interneurons are born relatively late during embryonic development in the ventral telencephalon and migrate dorsally to reach stereotypic positions in cortical laminae. Different patterns of early neuronal activity can be detected in migrating interneurons and after they reach their laminar destination. However, the significance of early activity for subtype maturation is not understood. We sought to assess the role of activity in the maturation of CGE-interneuron subtypes. To manipulate the excitability of developing interneurons, we targeted the expression of the inward rectifying potassium channel Kir2.1 to CGE-derived interneurons. We overexpress the channel under the Dlx5/6 enhancer element by means of in utero electroporation. The high levels of GFP expression achieved with this approach allowed for the detailed characterization of neuronal morphologies. Our experiments revealed that calretinin (Cr) and reelin (Re)-expressing CGE-derived interneurons exhibit marked defects in axonal arborization. In addition, Re interneurons show simple dendritic arbors and a concomitant defect in the kinetics of excitatory synaptic inputs. In contrast, vasointestinal peptide (VIP)-expressing interneurons are not affected by changes in membrane excitability. In addition, Cr and Re interneurons fail to migrate to appropriate laminae and occupy deeper layers in the somatosensory cortex. By using a suppressible genetic strategy, we found that neuronal activity is required cell-autonomously and independently at different developmental stages to determine neuronal morphology and layer positioning of select CGE-derived interneuron subtypes. Cr and Re interneuron silencing between postnatal day 2 (P2) and P3 perturbs laminar targeting whereas the development of neuronal morphology is unaffected. In contrast, reduction in neuronal excitability after P3 impairs the proper development of axons and dendrites. Blockade of synaptic transmission has no effect on either migration or morphology suggesting that the cell-autonomous release of GABA is not required for subtype specification. By contrast, we observed that pharmacological suppression of glutamatergic transmission phenocopied the morphological defects observed in Cr ant Re-expressing interneuron populations. We conclude that in these populations activity is sequentially required for the selection of laminar position and differentiation of select populations of cortical interneurons. Conference: EMBO workshop: Gaba Signalling and Brain Networks , Amsterdam, Netherlands, 30 Jun - 2 Jul, 2010. Presentation Type: Oral Presentation Topic: Talks Citation: DeMarco N, G F and T K (2010). The Selective requirement of Activity in maturation of specific cortical interneuron populations.. Conference Abstract: EMBO workshop: Gaba Signalling and Brain Networks . doi: 10.3389/conf.fnins.2010.15.00030 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 22 Jun 2010; Published Online: 22 Jun 2010. * Correspondence: N. DeMarco, NYU Langone Medical Center, Smilow Neuroscience Program and the Departments of Cell Biology and Neural Science, New York, United States, gordon.fishell@med.nyu.edu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers N. DeMarco Fishell G Karayannis T Google N. DeMarco Fishell G Karayannis T Google Scholar N. DeMarco Fishell G Karayannis T PubMed N. DeMarco Fishell G Karayannis T Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Gabaergic interneurons Help Bridge the Brain's Communication Gap

Event Abstract Back to Event Gabaergic interneurons Help Bridge the Brain's Communication Gap S. Garel1, P. Gaspar2, F. Guillemot3, J. Hornung4, C. Lebrand4*, F. Mann5, M. Niquille4, B. Otsmane5, C. Parras6 and Y. Yanagawa7 1 Ecole Normale Supérieure, Inserm, U784, France 2 Institut du Fer à Moulin, INSERM U839, France 3 National Institute for Medical Research, Mill Hill, Division of Molecular Neurobiology, United Kingdom 4 University of Lausanne, Department of Cellular Biology and Morphology, Switzerland 5 Developmental Biology Institute of Marseille Luminy, Université de la Méditerranée, CNRS, UMR 6216, France 6 Laboratoire de Biologie des Interactions Neurones/Glie Inserm, U-711, France 7 Gunma University Graduate School of Medicine and SORST, Department of Genetic and Behavioral Neuroscience, Japan Subpopulations of midline glial cells have been shown to guide corpus callosum (CC) axons to the contralateral cerebral hemisphere. While neuronal cells are also present in the developing CC, their role remains obscure. In our work, we show that the CC is transiently populated by numerous glutamatergic and GABAergic neurons. These two distinct neuronal populations converge towards the midline before the callosal axons. Time-lapse and 3D imaging studies reveal that these migrating neurons settle in CC and cooperate to form barriers that funnel callosal fibres. In vivo analyses in Mash1 mutant mice which lack CC GABAergic interneurons, and rescue experiments after transplantation of wild-type CC within Mash1-/- brain slices, demonstrate that CC GABAergic interneurons are essential to guide callosal axons at the midline. Moreover, in transplantation experiments of CC neurons into heterotopic regions, both types of CC neurons facilitate the growth of callosal fibres. Finally, Semaphorin 3C (Sema3C), which is expressed by CC glutamatergic neurons, acts through neuropilin 1 (Npn-1) to elicit an attractive action on callosal axons. Taken together, our study reveals a novel role for transient neuronal populations in the development of a major cerebral commissure and brings a new perspective on the respective roles of glial and neuronal cells in this process. Conference: EMBO workshop: Gaba Signalling and Brain Networks , Amsterdam, Netherlands, 30 Jun - 2 Jul, 2010. Presentation Type: Poster Presentation Topic: Posters Citation: Garel S, Gaspar P, Guillemot F, Hornung J, Lebrand C, Mann F, Niquille M, Otsmane B, Parras C and Yanagawa Y (2010). Gabaergic interneurons Help Bridge the Brain's Communication Gap. Conference Abstract: EMBO workshop: Gaba Signalling and Brain Networks . doi: 10.3389/conf.fnins.2010.15.00014 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 24 Jun 2010; Published Online: 24 Jun 2010. * Correspondence: C. Lebrand, University of Lausanne, Department of Cellular Biology and Morphology, Lausanne, Switzerland, cecile.lebrand@unil.ch Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers S. Garel P. Gaspar F. Guillemot J. Hornung C. Lebrand F. Mann M. Niquille B. Otsmane C. Parras Y. Yanagawa Google S. Garel P. Gaspar F. Guillemot J. Hornung C. Lebrand F. Mann M. Niquille B. Otsmane C. Parras Y. Yanagawa Google Scholar S. Garel P. Gaspar F. Guillemot J. Hornung C. Lebrand F. Mann M. Niquille B. Otsmane C. Parras Y. Yanagawa PubMed S. Garel P. Gaspar F. Guillemot J. Hornung C. Lebrand F. Mann M. Niquille B. Otsmane C. Parras Y. Yanagawa Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Redundant functions of Dvl1 and Dvl3 in amygdala organization and development mediates normal fear responses

Event Abstract Back to Event Redundant functions of Dvl1 and Dvl3 in amygdala organization and development mediates normal fear responses Andrea Chiba1, Leah S. Etheridge2*, Joy Greer2, Patricia LaPorte2, Jeffrey Long2, Jin Nakatani3, Lisa Stefanacci4 and Anthony Wynshaw-Boris2 1 University of California, Department of Cognitive Science , United States 2 University of California San Diego, Department of Pediatrics, School of Medicine, United States 3 University of California, Department of Pediatrics and Institute for Human Genetics, San Francisco School of Medicine, United States 4 The Salk Institute , United States The amygdala complex integrates sensory information with affect and cognition to affect the output of behavior, and is critical for both social behavior and fear responses. Although several ligand-receptor pairs and neurotransmitters such as GABA are known to modulate amygdala responses, the precise molecular mechanisms regulating the development of the amygdala and its responses are poorly understood. Based on the social behavior defects displayed by Dvl1 mutant mice and the redundant functions of the three Dvl genes during development, we examined double viable Dvl mutants for functional and structural amygdala defects. Surprisingly, we found that Dvl1-/-;Dvl3+/- mice display novel fear associated behavioral deficits attributable to specific and selective abnormalities in the amygdala. These include cellular disorganization, an increased number of GABA-positive neurons, and severely truncated dendritic morphology that occur post-natally. These findings implicate Dvl genes in amygdala development and define a molecular mechanism for the integration and organization of the amygdala via the developmental regulation of the production of GABA-positive neurons. Conference: EMBO workshop: Gaba Signalling and Brain Networks , Amsterdam, Netherlands, 30 Jun - 2 Jul, 2010. Presentation Type: Oral Presentation Topic: Talks Citation: Chiba A, Etheridge LS, Greer J, LaPorte P, Long J, Nakatani J, Stefanacci L and Wynshaw-Boris A (2010). Redundant functions of Dvl1 and Dvl3 in amygdala organization and development mediates normal fear responses. Conference Abstract: EMBO workshop: Gaba Signalling and Brain Networks . doi: 10.3389/conf.fnins.2010.15.00049 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 25 Jun 2010; Published Online: 25 Jun 2010. * Correspondence: Leah S Etheridge, University of California San Diego, Department of Pediatrics, School of Medicine, La Jolla, United States, WynshawBorisT@peds.ucsf.edu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Andrea Chiba Leah S Etheridge Joy Greer Patricia LaPorte Jeffrey Long Jin Nakatani Lisa Stefanacci Anthony Wynshaw-Boris Google Andrea Chiba Leah S Etheridge Joy Greer Patricia LaPorte Jeffrey Long Jin Nakatani Lisa Stefanacci Anthony Wynshaw-Boris Google Scholar Andrea Chiba Leah S Etheridge Joy Greer Patricia LaPorte Jeffrey Long Jin Nakatani Lisa Stefanacci Anthony Wynshaw-Boris PubMed Andrea Chiba Leah S Etheridge Joy Greer Patricia LaPorte Jeffrey Long Jin Nakatani Lisa Stefanacci Anthony Wynshaw-Boris Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

The vesicular GABA transporter VGAT is targeted to a distinct set of synaptic vesicles

Event Abstract Back to Event The vesicular GABA transporter VGAT is targeted to a distinct set of synaptic vesicles Jean-Luc Boulland1 and Farrukh A. Chaudhry1* 1 University of Oslo, The Biotechnology Centre and Centre for Molecular Biology and Neuroscience, Norway After its exocytotic release, GABA may be translocated into nerve terminals for reuse, or transported to perisynaptic glial processes where it is converted to glutamine which then is transported back to the nerve terminals for regeneration of GABA. We have characterized a family of glutamine transporters (Slc38) and demonstrated their involvement in this GABA-glutamine cycle. We have shown that the system N transporter SN1 is enriched on perisynaptic glial processes where it mediates release of glutamine. Glutamine uptake into neurons is mediated by system A transporters and SAT1 is particularly pronounced in GABAergic neurons. Subsequently the vesicular GABA transporter VGAT mediates accumulation of GABA into synaptic vesicles. Interestingly, VGAT may colocalize transiently during development or permanently with vesicular transporters for other transmitters. We have demonstrated expression of VGAT and the vesicular glutamate transporter VGLUT2 on distinct subpopulations of vesicles within a set of hippocampal nerve terminals in adult rat. Our data implicate differential release of multiple neurotransmitters from single nerve terminals in a set of GABAergic neurons. Conference: EMBO workshop: Gaba Signalling and Brain Networks , Amsterdam, Netherlands, 30 Jun - 2 Jul, 2010. Presentation Type: Poster Presentation Topic: Posters Citation: Boulland J and Chaudhry FA (2010). The vesicular GABA transporter VGAT is targeted to a distinct set of synaptic vesicles. Conference Abstract: EMBO workshop: Gaba Signalling and Brain Networks . doi: 10.3389/conf.fnins.2010.15.00005 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 23 Jun 2010; Published Online: 23 Jun 2010. * Correspondence: Farrukh A Chaudhry, University of Oslo, The Biotechnology Centre and Centre for Molecular Biology and Neuroscience, Oslo, Norway, f.a.chaudhry@biotek.uio.no Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Jean-Luc Boulland Farrukh A Chaudhry Google Jean-Luc Boulland Farrukh A Chaudhry Google Scholar Jean-Luc Boulland Farrukh A Chaudhry PubMed Jean-Luc Boulland Farrukh A Chaudhry Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

GABA signals modulate neuronal production

Event Abstract Back to Event GABA signals modulate neuronal production Angelique Bordey1* 1 Yale School of Medicine, Department of Signal Processing, United States The neurotransmitter gamma-aminobutyric acid (GABA) acting at GABAA receptors is critical for multiple developmental processes such as cell proliferation, migration, neurite extension, and network integration. Recent work has emphasized the importance of GABA on postnatal neurogenesis including the hippocampal subgranular zone and the subventricular zone (SVZ). The SVZ is the largest neurogenic zone where 10,000-30,000 neurons are produced per day and integrate in the olfactory bulb network. In this region, GABA exerts a negative feedback on neural progenitor cell proliferation and regulates neuroblast migration and differentiation. However, the ultimate in vivo function of GABA on SVZ neurogenesis remains unknown. To address this issue, we took advantage of and manipulated the depolarizing action of GABA. GABA effect is thought to result from its depolarization-induced calcium increases in both SVZ astrocytes and neuroblasts. We used a RNA interference approach against the Na-K-2Cl co-transporter 1 (NKCC1), which allows Cl- influx in immature cells, to reduce or eliminate GABA depolarization. Short hairpin RNA (shRNA) and a fluorescent reporter (GFP or RFP) were introduced into neural progenitor cells using in vivo electroporation in neonates. Using electrophysiology and calcium imaging, we found that shRNA expression to knock down (KD) NKCC1 (noted NKCC1KD) led to a premature hyperpolarization in neuroblasts integrating into the olfactory bulb network. We also found that 40% fewer NKCC1KD neuroblasts reached the olfactory bulb. This effect was not due to cell apoptosis measured with activated caspase-3 staining or a defect in cell migration. Indeed, NKCC1KD neuroblasts migrated at the same speed as neuroblasts containing a control shRNA. Finally, newly integrated NKCC1KD neurons displayed morphological defects compared to control. In conclusion, modulating NKCC1 expression in vivo significantly decreases the numbers of newly born neurons in the olfactory bulb and alters their morphology. Since there is a lack of either apoptotic or migratory defects, there is likely a proliferation defect in the astrocyte-like stem cells, neuroblasts, or potentially both. Conference: EMBO workshop: Gaba Signalling and Brain Networks , Amsterdam, Netherlands, 30 Jun - 2 Jul, 2010. Presentation Type: Oral Presentation Topic: Talks Citation: Bordey A (2010). GABA signals modulate neuronal production. Conference Abstract: EMBO workshop: Gaba Signalling and Brain Networks . doi: 10.3389/conf.fnins.2010.15.00028 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 22 Jun 2010; Published Online: 22 Jun 2010. * Correspondence: Angelique Bordey, Yale School of Medicine, Department of Signal Processing, New Haven, United States, angelique.bordey@yale.edu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Angelique Bordey Google Angelique Bordey Google Scholar Angelique Bordey PubMed Angelique Bordey Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Axonal variability of GABAergic ivy interneurons in the hippocampal CA1 area

Event Abstract Back to Event Axonal variability of GABAergic ivy interneurons in the hippocampal CA1 area D. Asede1, M. Capogna1, K. Lamsa2, D. Lapray1*, W. Nissen2, P. Somogyi1 and A. Szabo2 1 University of Oxford, Medical Research Council, Anatomical Neuropharmacology Unit, United Kingdom 2 University of Oxford, Department of Pharmacology, United Kingdom Pyramidal cells in CA1 receive spatially segregated glutamatergic input from the CA3 area in stratum oriens and radiatum on the one hand, and from the entorhinal cortex in stratum lacunosum moleculare on the other. Both local GABAergic ivy and neurogliaform cells express NOS and NPY, have a dense axonal field, and mediate slow synaptic transmission. However, ivy cells associate their axonal arbour with the CA3 input, whereas neurogliaform cells associate their axonal arbour with the entorhinal cortex input. This suggests an input pathway specific modulation of pyramidal cell activity by these cell types. Here we explored the variability in the axonal output of these two related interneuron types by recording cells in acute brain slices in vitro from juvenile rats (P21-28) and labelling them with neurobiotin. Individual ivy cells innervated either mainly stratum oriens, or stratum radiatum, or both equally. Here we show that unlike the axon of previously reported ivy cells, some of these interneurons also innervate stratum lacunosum moleculare to various degrees. Individual neurogliaform cells innervated only stratum lacunosum moleculare, or in addition the molecular layer of the dentate gyrus, or stratum lacunosum moleculare and stratum radiatum. Thus, it appears that there is overlap between the axonal output of ivy and neurogliaform cell populations. Because the dendritic trees of these interneurons may be completely within one of the two major glutamatergic input zones to CA1, their axons innervating the other input zone could potentially provide cross-modulatory influence. It needs to be further explored if the frequency of cells with axons of different laminar distribution varies along the septo-temporal axis of the hippocampus and whether they express different signalling molecules. Conference: EMBO workshop: Gaba Signalling and Brain Networks , Amsterdam, Netherlands, 30 Jun - 2 Jul, 2010. Presentation Type: Poster Presentation Topic: Posters Citation: Asede D, Capogna M, Lamsa K, Lapray D, Nissen W, Somogyi P and Szabo A (2010). Axonal variability of GABAergic ivy interneurons in the hippocampal CA1 area. Conference Abstract: EMBO workshop: Gaba Signalling and Brain Networks . doi: 10.3389/conf.fnins.2010.15.00013 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 24 Jun 2010; Published Online: 24 Jun 2010. * Correspondence: D. Lapray, University of Oxford, Medical Research Council, Anatomical Neuropharmacology Unit, Oxford, United Kingdom, damien.lapray@pharm.ox.ac.uk Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers D. Asede M. Capogna K. Lamsa D. Lapray W. Nissen P. Somogyi A. Szabo Google D. Asede M. Capogna K. Lamsa D. Lapray W. Nissen P. Somogyi A. Szabo Google Scholar D. Asede M. Capogna K. Lamsa D. Lapray W. Nissen P. Somogyi A. Szabo PubMed D. Asede M. Capogna K. Lamsa D. Lapray W. Nissen P. Somogyi A. Szabo Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Role of the neuron-specific isoform of neurofibromin in learning impairment in a mouse model of neurofibromatosis 1

Event Abstract Back to Event Role of the neuron-specific isoform of neurofibromin in learning impairment in a mouse model of neurofibromatosis 1 Y. Elgersma1, A. Omrani1* and G. Van Woerden1 1 Erasmus MC, Department of Neuroscience, Netherlands Neurofibromatosis type I (NF1) is an autosomal dominant disorder and is commonly associated with cognitive problems. Previous studies indicated that mice heterozygous for a null mutation in NF1 show impairment of visual-spatial learning and long-term potentiation (LTP) in the hippocampus that arises from increased activity of Ras pathway in interneurons. Although NF1 is expressed in all cells of the central nervous system, expression of NF1 containing alternatively spliced exon 9a is restricted to neurons. The existence of an evolutionary conserved neuron-specific isoform of neurofibromin raises the possibility that this isoform has unique properties by virtue of the presence of exon 9a and that this exon may have an important role on neurofibromin function in neurons. However, the functional significance of this neuron-specific NF1 isoform is unknown. To study the role of exon 9a in function of neurofibromin in neurons, we generated mice lacking the NF1-exone 9a isoform. Interestingly, our data show that mice lacking NF1-exon 9a have spatial learning and LTP deficits that arise from an increase in GABA-mediated inhibition in the hippocampus. In addition, we show that enhanced-GABA release in our mutants is caused by overactive ERK signaling in hippocampal interneurons. These data indicate that exon 9a is indeed critical for neurofibromin function in neurons. It is likely that this exon has a modulatory effect on Ras-GAP activity of neurofibromin in neurons. Conference: EMBO workshop: Gaba Signalling and Brain Networks , Amsterdam, Netherlands, 30 Jun - 2 Jul, 2010. Presentation Type: Poster Presentation Topic: Posters Citation: Elgersma Y, Omrani A and Van Woerden G (2010). Role of the neuron-specific isoform of neurofibromin in learning impairment in a mouse model of neurofibromatosis 1. Conference Abstract: EMBO workshop: Gaba Signalling and Brain Networks . doi: 10.3389/conf.fnins.2010.15.00017 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 24 Jun 2010; Published Online: 24 Jun 2010. * Correspondence: A. Omrani, Erasmus MC, Department of Neuroscience, Rotterdam, Netherlands, a.omrani@erasmusmc.nl Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Y. Elgersma A. Omrani G. Van Woerden Google Y. Elgersma A. Omrani G. Van Woerden Google Scholar Y. Elgersma A. Omrani G. Van Woerden PubMed Y. Elgersma A. Omrani G. Van Woerden Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

The roles of GABAergic inhibitions in the striatum network in normal and dopamine-depleted states

Event Abstract Back to Event The roles of GABAergic inhibitions in the striatum network in normal and dopamine-depleted states Man Y. Yim1*, Arvind Kumar2 and Ad Aertsen1, 2 1 Bernstein Center Freiburg, Germany 2 Albert-Ludwig University, Neurobiology and Biophysics, Faculty of Biology, Germany Medium spiny neurons (MSNs) are GABAergic neurons representing over 95% of the striatum neuron population. Based on the expression of dopamine receptors, MSNs can be divided into two subpopulations, D1- and D2-MSNs, which project to the basal ganglia (BG) output via the direct and indirect pathways, respectively. The duration of dopamine depletion has distinct effects on striatal activity. Acute dopamine depletion decreases D1- and increases D2-MSNs' activity. By contrast, chronic depletion increases the activity of both subpopulations. To understand the effects of dopamine-induced firing rate changes of D1- and D2-MSNs on the activity dynamics of striatum, we simulated a biologically realistic striatal network model. The model was characterized by weak feedback inhibition and strong feedforward inhibition from interneurons. In the normal state we assumed D1- and D2-MSNs had comparable firing rates. To simulate dopamine depleted states of the striatum, we systematically changed the firing rates of the D1- and D2-MSNs. We found that an increase in firing rate of one or both subpopulations enhanced the output correlation and might drive the network into oscillation, mediated by recurrent inhibition. The increased correlation in D2-MSNs may play a role in shaping oscillations in the BG, associated with the Parkinson's disease state. Supported by the German Federal Ministry of Education and Research (BMBF 01GQ0420 to BCCN Freiburg, BMBF GW0542 Cognition and BMBF 01GW0730 Impulse Control). Conference: EMBO workshop: Gaba Signalling and Brain Networks , Amsterdam, Netherlands, 30 Jun - 2 Jul, 2010. Presentation Type: Poster Presentation Topic: Posters Citation: Yim MY, Kumar A and Aertsen A (2010). The roles of GABAergic inhibitions in the striatum network in normal and dopamine-depleted states. Conference Abstract: EMBO workshop: Gaba Signalling and Brain Networks . doi: 10.3389/conf.fnins.2010.15.00027 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 25 Jun 2010; Published Online: 25 Jun 2010. * Correspondence: Man Y Yim, Bernstein Center Freiburg, Freiburg, Germany, yim@bcf.uni-freiburg.de Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Man Y Yim Arvind Kumar Ad Aertsen Google Man Y Yim Arvind Kumar Ad Aertsen Google Scholar Man Y Yim Arvind Kumar Ad Aertsen PubMed Man Y Yim Arvind Kumar Ad Aertsen Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Evoking action potentials by dis-inhibition in neocortex during high-conductance states

Event Abstract Back to Event Evoking action potentials by dis-inhibition in neocortex during high-conductance states Alain Destexhe1* 1 CNRS, UNIC, France Evidence indicate that cortical neurons may operate in high-conductance states, in which the major part of the neuron’s input conductance is due to synaptic activity, sometimes several-fold larger than the resting conductance. Such states were studied using a combination of computational models and intracellular recordings. Models indicate that in low-conductance states, the majority of spikes are correlated with a prior increase of excitatory conductance, but during high-conductance states, spikes are correlated to a prior decrease of inhibitory conductance or dis-inhibition. This paradigm was tested in dynamic-clamp experiments in guinea-pig visual cortex in vitro, and the same conclusions were found. To test the presence of such dis-inhibition, we conceived probabilistic methods to extract the spike-triggered average of synaptic conductances from Vm recordings. Applying this procedure to intracellular recordings of cortical neurons in awake animals revealed that indeed, most spikes were correlated to a prior dis-inhibition. These results argue against a «feedforward» scheme for information transmission in neocortex, but suggest that spiking activity is strongly constrained by recurrent network activity. Supported by CNRS, ANR and the European Community (FACETS project). Conference: EMBO workshop: Gaba Signalling and Brain Networks , Amsterdam, Netherlands, 30 Jun - 2 Jul, 2010. Presentation Type: Oral Presentation Topic: Talks Citation: Destexhe A (2010). Evoking action potentials by dis-inhibition in neocortex during high-conductance states. Conference Abstract: EMBO workshop: Gaba Signalling and Brain Networks . doi: 10.3389/conf.fnins.2010.15.00044 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 24 Jun 2010; Published Online: 24 Jun 2010. * Correspondence: Alain Destexhe, CNRS, UNIC, Gif sur Yvette, France, destexhe@unic.cnrs-gif.fr Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Alain Destexhe Google Alain Destexhe Google Scholar Alain Destexhe PubMed Alain Destexhe Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Direct Action of two major Antidepressants on a Specific Inhibitory Circuit of the Hippocampus

Event Abstract Back to Event Direct Action of two major Antidepressants on a Specific Inhibitory Circuit of the Hippocampus A. Bacci1, P. Mendez1* and A. Pazienti1 1 European Brain Research Institute, Italy Hippocampal inhibitory synapses innervating the perisomatic region of principal pyramidal neurons originate from different basket cell subtypes. Specific properties of these inhibitory synapses differently control hippocampal functions. Fast-spiking (FS) interneurons exert a tight temporal control of network activities, and support feed-forward inhibition. Conversely, cannabinoid receptor 1(CB1R)-positive basket cells generate feedback inhibition and were proposed to control mood and emotional states. Alterations of GABA release from specific soma-targeting interneurons might thus result in mood disorders. Here we studied the effects on inhibitory neurotransmission onto CA1 hippocampal pyramidal cells of two major antidepressants: imipramine, a tricyclic antidepressant and fluoxetine, a selective serotonin reuptake inhibitor. Application of either drug strongly reduced evoked inhibitory postsynaptic currents and increased the excitation-inhibition ratio on pyramidal neurons in acute slices from rodents. These effects had a presynaptic origin and were independent of the known actions of these drugs on aminergic reuptake systems. Interestingly, antidepressants affected selective inhibitory circuits, as both drugs reduced feed-forward inhibition, leaving the CB1R-sensitive feedback loop unaffected. Pair recordings of unitary synaptic responses between identified basket cells and pyramidal neurons showed that these antidepressants reduced inhibition originating from FS cells, but not from CB1R+ interneurons. Despite their widespread use in clinic, the precise mechanism of action of antidepressant drugs is still debated. Our results demonstrate that hippocampal inhibitory circuits are selectively and directly affected by two major antidepressants and suggest a new mechanism of action of these drugs in the central nervous system. We are currently testing how this selective suppression of feed-forward inhibition affects network hippocampal activities. Conference: EMBO workshop: Gaba Signalling and Brain Networks , Amsterdam, Netherlands, 30 Jun - 2 Jul, 2010. Presentation Type: Poster Presentation Topic: Posters Citation: Bacci A, Mendez P and Pazienti A (2010). Direct Action of two major Antidepressants on a Specific Inhibitory Circuit of the Hippocampus. Conference Abstract: EMBO workshop: Gaba Signalling and Brain Networks . doi: 10.3389/conf.fnins.2010.15.00016 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 24 Jun 2010; Published Online: 24 Jun 2010. * Correspondence: P. Mendez, European Brain Research Institute, Rome, Italy, p.mendez@ebri.it Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers A. Bacci P. Mendez A. Pazienti Google A. Bacci P. Mendez A. Pazienti Google Scholar A. Bacci P. Mendez A. Pazienti PubMed A. Bacci P. Mendez A. Pazienti Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Extrasynaptic GABAergic currents in hippocampus are inhibited by adenosine A1 receptors

Event Abstract Back to Event Extrasynaptic GABAergic currents in hippocampus are inhibited by adenosine A1 receptors R. Dias1, J. Ribeiro1, D. Rombo1* and A. Sebastião1 1 Instituto de Farmacologia e Neurociências, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Portugal Adenosine, through inhibitory A1 receptors is a modulator of neuronal excitability in the hippocampus by modulating the glutamatergic excitatory circuit at the pre- and postsynaptic level. The role of adenosine on GABAergic transmission in the hippocampus is much less known. We now investigated whether adenosine, through A1 receptors, modulates postsynaptic currents mediated by GABAA receptors. Muscimol (30µM, GABAA receptor agonist)-evoked postsynaptic currents (PSCs), afferent-evoked inhibitory postsynaptic currents (IPSCs) and miniature inhibitory postsynaptic currents (mIPSCs), were recorded (whole-cell configuration, Vh=-80mV) from CA1 pyramidal cells and interneurons of rat (Wistar, 3-5w) hippocampal slices. At CA1 pyramidal cells, the activation of A1 receptors with CPA (10-30nM) decreased (to 54±3.9%,p<0.0001,n=12) the peak amplitude of PSCs and this inhibition was reversed by DPCPX (50nM), an adenosine A1 receptor antagonist, to 83±2.5% of baseline (n=4,p<0.05). DPCPX per se unmasked the inhibition of PSCs by endogenous extracellular adenosine since it increased the inhibitory currents by 13±1.0% (n=5,p<0.001). Neither the amplitude nor the frequency of mIPSCs (n=12), or the amplitude of IPSCs (n=10), were affected by CPA indicating an action of A1 receptors on extrasynaptic GABAergic currents. At stratum radiatum GABAergic interneurons, the activation of A1 receptors with CPA attenuated GABAA PSCs in 4 out of 9 cells tested to 57±2.3% (p<0.001). The PSCs in the other 5 cells tested were not changed by CPA superfusion, suggesting the existence of two populations of interneurons differently sensitive to adenosine. Together, these results indicate that extrasynaptic GABAA receptor-mediated currents are modulated by adenosine A1 receptors in pyramidal hippocampal neurons and in a subset of interneurons. Support:FCT Conference: EMBO workshop: Gaba Signalling and Brain Networks , Amsterdam, Netherlands, 30 Jun - 2 Jul, 2010. Presentation Type: Poster Presentation Topic: Posters Citation: Dias R, Ribeiro J, Rombo D and Sebastião A (2010). Extrasynaptic GABAergic currents in hippocampus are inhibited by adenosine A1 receptors. Conference Abstract: EMBO workshop: Gaba Signalling and Brain Networks . doi: 10.3389/conf.fnins.2010.15.00021 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 24 Jun 2010; Published Online: 24 Jun 2010. * Correspondence: D. Rombo, Instituto de Farmacologia e Neurociências, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal, drombo@fm.ul.pt Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers R. Dias J. Ribeiro D. Rombo A. Sebastião Google R. Dias J. Ribeiro D. Rombo A. Sebastião Google Scholar R. Dias J. Ribeiro D. Rombo A. Sebastião PubMed R. Dias J. Ribeiro D. Rombo A. Sebastião Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.