Population Of Inhibitory Interneurons Research Articles

Distribution of the Octopamine Receptor AmOA1 in the Honey Bee Brain

Octopamine plays an important role in many behaviors in invertebrates. It acts via binding to G protein coupled receptors located on the plasma membrane of responsive cells. Several distinct subtypes of octopamine receptors have been found in invertebrates, yet little is known about the expression pattern of these different receptor subtypes and how each subtype may contribute to different behaviors. One honey bee (Apis mellifera) octopamine receptor, AmOA1, was recently cloned and characterized. Here we continue to characterize the AmOA1 receptor by investigating its distribution in the honey bee brain. We used two independent antibodies produced against two distinct peptides in the carboxyl-terminus to study the distribution of the AmOA1 receptor in the honey bee brain. We found that both anti-AmOA1 antibodies revealed labeling of cell body clusters throughout the brain and within the following brain neuropils: the antennal lobes; the calyces, pedunculus, vertical (alpha, gamma) and medial (beta) lobes of the mushroom body; the optic lobes; the subesophageal ganglion; and the central complex. Double immunofluorescence staining using anti-GABA and anti-AmOA1 receptor antibodies revealed that a population of inhibitory GABAergic local interneurons in the antennal lobes express the AmOA1 receptor in the cell bodies, axons and their endings in the glomeruli. In the mushroom bodies, AmOA1 receptors are expressed in a subpopulation of inhibitory GABAergic feedback neurons that ends in the visual (outer half of basal ring and collar regions) and olfactory (lip and inner basal ring region) calyx neuropils, as well as in the collar and lip zones of the vertical and medial lobes. The data suggest that one effect of octopamine via AmOA1 in the antennal lobe and mushroom body is to modulate inhibitory neurons.

Galanin-Immunoreactivity Identifies a Distinct Population of Inhibitory Interneurons in Laminae I-III of the Rat Spinal Cord

BackgroundInhibitory interneurons constitute 30-40% of neurons in laminae I-III and have an important anti-nociceptive role. However, because of the difficulty in classifying them we know little about their organisation. Previous studies have identified 3 non-overlapping groups of inhibitory interneuron, which contain neuropeptide Y (NPY), neuronal nitric oxide synthase (nNOS) or parvalbumin, and have shown that these differ in postsynaptic targets. Some inhibitory interneurons contain galanin and the first aim of this study was to determine whether these form a different population from those containing NPY, nNOS or parvalbumin. We also estimated the proportion of neurons and GABAergic axons that contain galanin in laminae I-III.ResultsGalanin cells were concentrated in laminae I-IIo, with few in laminae IIi-III. Galanin showed minimal co-localisation with NPY, nNOS or parvalbumin in laminae I-II, but most galanin-containing cells in lamina III were nNOS-positive. Galanin cells constituted ~7%, 3% and 2% of all neurons in laminae I, II and III, and we estimate that this corresponds to 26%, 10% and 5% of the GABAergic neurons in these laminae. However, galanin was only found in ~6% of GABAergic boutons in laminae I-IIo, and ~1% of those in laminae IIi-III.ConclusionsThese results show that galanin, NPY, nNOS and parvalbumin can be used to define four distinct neurochemical populations of inhibitory interneurons. Together with results of a recent study, they suggest that the galanin and NPY populations account for around half of the inhibitory interneurons in lamina I and a quarter of those in lamina II.

Dynorphin is Expressed Primarily by GABAergic Neurons That Contain Galanin in the Rat Dorsal Horn

BackgroundThe opioid peptide dynorphin is expressed by certain neurons in the superficial dorsal horn of the spinal cord, but little is known about the types of cell that contain dynorphin. In this study, we have used an antibody against the dynorphin precursor preprodynorphin (PPD), to reveal the cell bodies and axons of dynorphin-expressing neurons in the rat spinal cord. The main aims were to estimate the proportion of neurons in each of laminae I-III that express dynorphin and to determine whether they are excitatory or inhibitory neurons.ResultsPPD-immunoreactive cells were concentrated in lamina I and the outer part of lamina II (IIo), where they constituted 17% and 8%, respectively, of all neurons. Around half of those in lamina I and 80% of those in lamina II were GABA-immunoreactive. We have previously identified four non-overlapping neurochemical populations of inhibitory interneurons in this region, defined by the presence of neuropeptide Y, galanin, parvalbumin and neuronal nitric oxide synthase. PPD co-localised extensively with galanin in both cell bodies and axons, but rarely or not at all with the other three markers. PPD was present in around 4% of GABAergic boutons (identified by the presence of the vesicular GABA transporter) in laminae I-II.ConclusionsThese results show that most dynorphin-expressing cells in the superficial dorsal horn are inhibitory interneurons, and that they largely correspond to the population that is defined by the presence of galanin. We estimate that dynorphin is present in ~32% of inhibitory interneurons in lamina I and 11% of those in lamina II. Since the proportion of GABAergic boutons that contain PPD in these laminae was considerably lower than this, our findings suggest that these neurons may generate relatively small axonal arborisations.

The Largest Group of Superficial Neocortical GABAergic Interneurons Expresses Ionotropic Serotonin Receptors

A highly diverse population of neocortical GABAergic inhibitory interneurons has been implicated in multiple functions in information processing within cortical circuits. The diversity of cortical interneurons is determined during development and primarily depends on their embryonic origins either from the medial (MGE) or the caudal (CGE) ganglionic eminences. Although MGE-derived parvalbumin (PV)- or somatostatin (SST)-expressing interneurons are well characterized, less is known about the other types of cortical GABAergic interneurons, especially those of CGE lineage, because of the lack of specific neuronal markers for these interneuron subtypes. Using a bacterial artificial chromosome transgenic mouse line, we show that, in the somatosensory cortex of the mouse, the serotonin 5-hydroxytryptamine 3A (5-HT(3A)) receptor, the only ionotropic serotonergic receptor, is expressed in most, if not all, neocortical GABAergic interneurons that do not express PV or SST. Genetic fate mapping and neurochemical profile demonstrate that 5-HT(3A)R-expressing neurons include the entire spectrum of CGE-derived interneurons. We report that, in addition to serotonergic responsiveness via 5-HT(3A)Rs, acetylcholine also depolarizes 5-HT(3A)R-expressing neurons via nicotinic receptors. 5-HT(3A)R-expressing neurons in thalamocortical (TC) recipient areas receive weak but direct monosynaptic inputs from the thalamus. TC input depolarizes a subset of TC-recipient 5-HT(3A)R neurons as strongly as fast-spiking cells, in part because of their high input resistance. Hence, fast modulation of serotonergic and cholinergic transmission may influence cortical activity through an enhancement of GABAergic synaptic transmission from 5-HT(3A)R-expressing neurons during sensory process depending on different behavioral states.

GABAA receptor diversity revealed in freeze-fracture replica (Commentary on Kasugai et al.)

GABAergic inputs from at least 18 types of inhibitory interneurons regulate and coordinate the activity of pyramidal cells in the hippocampal area CA1 (Klausberger et al., 2005), which in turn express at least 14 subunits of the GABAA receptor (GABAAR) with varying affinity to GABA and other ligands (Persohn et al., 1992; Wisden et al., 1992; Sperk et al., 1997; Ogurusu et al., 1999). Thus, the subunit composition determines the local response of the GABAAR to synaptically released GABA. Elucidating the subunit composition of synaptic and extrasynaptic GABAAR is also crucial in understanding the phasic vs. tonic postsynaptic responses evoked by GABA. In their elegant study, Kasugai et al. (2010) performed a series of double-labeling experiments to demonstrate for the first time that virtually all somatic inhibitory synapses in the rat hippocampal CA1 pyramidal cell contained α1, α2, and β3 subunits of GABAAR. The authors developed a new antibody against the α1 subunit to be used for a sensitive immunocytochemical method, freeze-fracture replica-immunogold labeling, that allows for quantitative analyses of transmembrane protein distribution (Fujimoto, 1995; Masugi-Tokita & Shigemoto, 2007). Their finding is consistent with previous post-embedding immunogold studies (Nusser et al., 1996; Somogyi et al., 1996). The presence of the three subunits in all somatic synapses does not imply that all synaptic GABAARs consist of these subunits. However, this finding raises an interesting question regarding the relative proportion of the subunits at these synapses, because previous studies showed that α1 and α2 subunits preferentially mediate inputs from fast-spiking and regular-spiking basket cells, respectively (Pawelzik et al., 1999; Thomson et al., 2000; Nyiri et al., 2001; Klausberger et al., 2002). Kasugai et al. (2010) also conducted single-labeling experiments to examine carefully the density of α1, α2 and β3 subunits in the synaptic and extrasynaptic plasma membrane of the pyramidal cells. Thirty to 50% of total labeling was found in synapses with 50–70% being extrasynaptic, suggesting that these subunits are well distributed between synaptic and extrasynaptic membrane. This is perhaps not too surprising as GABAARs diffuse laterally in the plasma membrane (Bannai et al., 2009). However, in light of previous studies suggesting that tonic inhibition is mediated by extrasynaptic GABAARs containing the α4, α5, α6 and/or δ subunits (Belelli et al., 2009), one might wonder how α1- or α2-containing extrasynaptic receptors are different from the synaptic ones in their subunit composition, targeting and functions. Elucidating the native subunit composition of GABAARs at identified synapses and extrasynaptic membrane will require a combination of research tools, including subunit-specific antibodies against different epitopes (intracellular vs. extracellular), transgenic animals (with specific subunits deleted or mutated in specific neuronal populations) and subunit-specific allosteric modulators. Studies on the interactions between specific subunit and scaffolding proteins would also provide insight into the mechanisms that target and regulate GABAARs. The data from this study provide a solid anatomical substrate to understand the functions of α1, α2 and β3 subunits in synaptic and extrasynaptic plasma membrane. They begin to elucidate how a diverse population of GABAARs and inhibitory interneurons may shape cortical network activity in health and disease.

An Itch To Be Scratched

The description of itch (formally known as pruritus) as an "unpleasant sensation that elicits the desire or reflex to scratch" (Ikoma et al., 2006) is immediately familiar. Research in the field of pruritoception has added to our understanding of this area of sensory neurobiology as it pertains to both normal and pathological conditions. In particular, much progress has been made on the mechanisms and circuits of itch, which we review here.

Populations of inhibitory and excitatory interneurons in lamina II of the adult rat spinal dorsal horn revealed by a combined electrophysiological and anatomical approach

Lamina II contains a large number of interneurons involved in modulation and transmission of somatosensory (including nociceptive) information. However, its neuronal circuitry is poorly understood due to the difficulty of identifying functional populations of interneurons. This information is important for understanding nociceptive processing and for identifying changes that underlie chronic pain. In this study, we compared morphology, neurotransmitter content, electrophysiological and pharmacological properties for 61 lamina II neurons recorded in slices from adult rat spinal cord. Morphology was related to transmitter content, since islet cells were GABAergic, while radial and most vertical cells were glutamatergic. However, there was considerable diversity among the remaining cells, some of which could not be classified morphologically. Transmitter phenotype was related to firing pattern, since most (18/22) excitatory cells, but few (2/23) inhibitory cells had delayed, gap or reluctant patterns, which are associated with A-type potassium (IA) currents. Somatostatin was identified in axons of 14/24 excitatory neurons. These had variable morphology, but most of those tested showed delayed-firing. Excitatory interneurons are therefore likely to contribute to pain states associated with synaptic plasticity involving IA currents. Although noradrenaline and serotonin evoked outward currents in both inhibitory and excitatory cells, somatostatin produced these currents only in inhibitory neurons, suggesting that its pro-nociceptive effects are mediated by disinhibition. Our results demonstrate that certain distinctive populations of inhibitory and excitatory interneuron can be recognised in lamina II. Combining this approach with identification of other neurochemical markers should allow further clarification of neuronal circuitry in the superficial dorsal horn.

Characterizing the temporal dynamics of cortical microcircuits: first and second order kernels for a cortical microcircuit

Neurons in the cerebral cortex form microcircuits that can be described as a network of feedforward and feedback, excitatory and inhibitory loops. It is, consequently, natural to represent cortical microcircuits as a control system (e.g. [1]) with thalamic inputs and outputs to other brain regions. The visual cortex in freshwater turtles contains pyramidal cells that receive inputs from the lateral geniculate nucleus and project to other cortical areas, the geniculate and structures in the brainstem [2]. It also contains at least three populations of inhibitory interneurons called subpial cells, stellate cells and horizontal cells [3]. We [4] have used a large-scale model of turtle visual cortex to characterize this cortex as a control system. However, this model is too large and complex to allow analysis with methods from control and systems theory, so we developed a dynamical systems model that consists of a family of linear non-autonomous ordinary differential equations. The activity of the ith population of neurons, , is given by the equation (1) . The summation is over the N populations of neurons. The time-dependent coefficients give the time course of synaptic interactions of all neurons in the ith population by all of the neurons in the jth population. The coefficients were determined by fitting the solutions of the equations (1) to the results of simulations using the large-scale model. In this study, we characterized the dynamics of the system (1) to pulses and pairs of pulses in order to determine the impulse response function (or first order kernel) and the higher order kernels of the system. The kernels are important because they describe the underlying temporal dynamics of the system. The first order kernel consists of two peaks, one at about 100 ms and one at about 600 ms after a pulse input. Blocking recurrent excitation between pyramidal cells shows that the recurrent excitation is responsible for a large gain in the system. Blocking specific populations of inhibitory interneurons with recurrent excitation intact shows that both feedforward and feedback inhibition control the magnitude of the pyramidal cell response. It also shows that specific populations of inhibitory interneurons interact with each other. The second order (first non-linear) kernel changes it shape as a function of the separation between the two pulses, and becomes zero with interpulse intervals of more than 50 ms. Blocking recurrent excitation between pyramidal cells or all inhibition in the system shows that both recurrent excitation and inhibition make major contributions to the non-linearity in the system. Specific types of inhibitory interneurons contribute to specific temporal phases of the second order kernel. The study suggests that cortical microcircuits have several general features. First, it confirms the concept that recurrent excitation plays a significant role in amplifying cortical inputs. Second, it suggests that the various populations of inhibitory interneurons interact with each other in a complex fashion so that an individual type of interneuron should not be assigned a unique function. Third, it suggests that the structure of the network is not static. It, rather, evolves with time depending on the temporal dynamics of the system.

Loss of Inhibitory Interneurons in the Dorsal Spinal Cord and Elevated Itch in Bhlhb5 Mutant Mice

Itch is the least well understood of all the somatic senses, and the neural circuits that underlie this sensation are poorly defined. Here we show that the atonal-related transcription factor Bhlhb5 is transiently expressed in the dorsal horn of the developing spinal cord and appears to play a role in the formation and regulation of pruritic (itch) circuits. Mice lacking Bhlhb5 develop self-inflicted skin lesions and show significantly enhanced scratching responses to pruritic agents. Through genetic fate-mapping and conditional ablation, we provide evidence that the pruritic phenotype in Bhlhb5 mutants is due to selective loss of a subset of inhibitory interneurons in the dorsal horn. Our findings suggest that Bhlhb5 is required for the survival of a specific population of inhibitory interneurons that regulate pruritus, and provide evidence that the loss of inhibitory synaptic input results in abnormal itch.

Targeted optogenetic stimulation and recording of neurons in vivo using cell-type-specific expression of Channelrhodopsin-2

A major long-term goal of systems neuroscience is to identify the different roles of neural subtypes in brain circuit function. The ability to causally manipulate selective cell types is critical to meeting this goal. This protocol describes techniques for optically stimulating specific populations of excitatory neurons and inhibitory interneurons in vivo in combination with electrophysiology. Cell type selectivity is obtained using Cre-dependent expression of the light-activated channel Channelrhodopsin-2. We also describe approaches for minimizing optical interference with simultaneous extracellular and intracellular recording. These optogenetic techniques provide a spatially and temporally precise means of studying neural activity in the intact brain and allow a detailed examination of the effect of evoked activity on the surrounding local neural network. Injection of viral vectors requires 30-45 min, and in vivo electrophysiology with optogenetic stimulation requires 1-4 h.

Finding your place when you are young: Recruitment of adult-generated neurons into song nucleus HVC

Event Abstract Back to Event Finding your place when you are young: Recruitment of adult-generated neurons into song nucleus HVC Sophie Scotto-Lomassese1, T. Roeske2, A. Garthe3 and Constance Scharff2* 1 Universite Pierre et Marie Curie, Laboratoire de Neurobiologie des Processus adaptatifs, France 2 Institute of Biology, Freie Universität Berlin, Department of Animal Behaviour, Germany 3 Center for Regenerative Therapies, Germany In adult songbirds, new neurons are born in the ventricular zone and after migration integrate into circuits throughout most of the telencephalon. New neurons also immigrate into HVC, a nucleus involved in song learning and production. HVC is composed of a heterogeneous population of inhibitory interneurons (HVCIN) and two populations of projection neurons that send axons towards the Robust nucleus of the Arcopallium (HVCRA) or the striatal nucleus Area X (HVCX). HVCRA neurons orchestrate the temporal sequence of the song via a sparse firing code. The renewal of this population raises the question whether old neurons perhaps instruct new ones. If cluster are connected via gap junctions, which are known to be expressed in HVC, they could potentially serve as functional units for new neurons to acquire their sparse song-related firing. We thus investigate the relative contribution of the different HVC cell types towards these clusters and whether new neurons integrate into particular cluster types using immunocytochemistry (cell birth and cell phenotype markers) in conjunction with stereotaxic injections of retrograde tracers into RA and Area X. Interestingly, we find that that 80% of the HVC neurons have one or more partners with direct soma contact. Clustering involved all neuron types, with two or three neurons per cluster the most common. HVCX neurons constitute 36% of HVC neurons and essentially all HVCX neurons were found in clusters. HVCRA neurons comprise 54% of HVC neurons and 80% occurred in clusters. Interneurons only contribute 10% of HVC neurons and 75% for HVCIN were found in clusters. 72% of new neurons were already incorporated into clusters one month after their birth. Moreover, these newly arriving cells did not associate with the most frequently encountered cluster type but preferentially joined the relatively rare single neurons or joined clusters of two cells. Thus, new neurons seem to participate in maintenance of the overall cluster distribution. We also analyzed the phenotype of the cell in direct contact with a new neuron and found that they are also not distributed according to frequency of occurrence of the different cell classes. Together, these results suggest that integration of new neurons into the HVC is not random and that clusters might participate in the regulation how new neurons incorporate into existing networks. Ultrastructural and intracellular dye injections are currently underway to clarify the presence of gap junctions between new and already existing neurons. Conference: 3rd Mediterranean Conference of Neuroscience , Alexandria, Egypt, 13 Dec - 16 Dec, 2009. Presentation Type: Oral Presentation Topic: Symposium 03 – Cellular regulation of adult-born neurons and their stem cells Citation: Scotto-Lomassese S, Roeske T, Garthe A and Scharff C (2009). Finding your place when you are young: Recruitment of adult-generated neurons into song nucleus HVC. Front. Neurosci. Conference Abstract: 3rd Mediterranean Conference of Neuroscience . doi: 10.3389/conf.neuro.01.2009.16.020 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: 19 Nov 2009; Published Online: 19 Nov 2009. * Correspondence: Constance Scharff, Institute of Biology, Freie Universität Berlin, Department of Animal Behaviour, Berlin, Germany, scharff@zedat.fu-berlin.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 Sophie Scotto-Lomassese T. Roeske A. Garthe Constance Scharff Google Sophie Scotto-Lomassese T. Roeske A. Garthe Constance Scharff Google Scholar Sophie Scotto-Lomassese T. Roeske A. Garthe Constance Scharff PubMed Sophie Scotto-Lomassese T. Roeske A. Garthe Constance Scharff 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.

Gamma oscillations mediate stimulus competition and attentional selection in a cortical network model

Simultaneous presentation of multiple stimuli can reduce the firing rates of neurons in extrastriate visual cortex below the rate elicited by a single preferred stimulus. We describe computational results suggesting how this remarkable effect may arise from strong excitatory drive to a substantial local population of fast-spiking inhibitory interneurons, which can lead to a loss of coherence in that population and thereby raise the effectiveness of inhibition. We propose that in attentional states fast-spiking interneurons may be subject to a bath of inhibition resulting from cholinergic activation of a second class of inhibitory interneurons, restoring conditions needed for gamma rhythmicity. Oscillations and coherence are emergent features, not assumptions, in our model. The gamma oscillations in turn support stimulus competition. The mechanism is a form of "oscillatory selection," in which neural interactions change phase relationships that regulate firing rates, and attention shapes those neural interactions.

Odor vapor pressure and quality modulate local field potential oscillatory patterns in the olfactory bulb of the anesthetized rat

A central question in chemical senses is the way that odorant molecules are represented in the brain. To date, many studies, when taken together, suggest that structural features of the molecules are represented through a spatio-temporal pattern of activation in the olfactory bulb (OB), in both glomerular and mitral cell layers. Mitral/tufted cells interact with a large population of inhibitory interneurons resulting in a temporal patterning of bulbar local field potential (LFP) activity. We investigated the possibility that molecular features could determine the temporal pattern of LFP oscillatory activity in the OB. For this purpose, we recorded the LFPs in the OB of urethane-anesthetized, freely breathing rats in response to series of aliphatic odorants varying subtly in carbon-chain length or functional group. In concordance with our previous reports, we found that odors evoked oscillatory activity in the LFP signal in both the beta and gamma frequency bands. Analysis of LFP oscillations revealed that, although molecular features have almost no influence on the intrinsic characteristics of LFP oscillations, they influence the temporal patterning of bulbar oscillations. Alcohol family odors rarely evoke gamma oscillations, whereas ester family odors rather induce oscillatory patterns showing beta/gamma alternation. Moreover, for molecules with the same functional group, the probability of gamma occurrence is correlated to the vapor pressure of the odor. The significance of the relation between odorant features and oscillatory regimes along with their functional relevance are discussed.

Imbalance of immunohistochemically characterized interneuron populations in the adolescent and adult rodent medial prefrontal cortex after repeated exposure to neonatal separation stress

Experimental studies in various animal models have revealed convincing evidence that stressful experience during early developmental periods produces a variety of behavioral, neuroanatomical and endocrine alterations, which are reminiscent of human mental disorders such as depression and various types of anxiety disorders. Since these mental disorders are assumed to be associated with altered GABAergic inhibition in cortical and subcortical brain regions, the current study tested the hypothesis that early postnatal adverse emotional experience (separation stress) interferes with the establishment and functional maturation of distinct inhibitory interneuron populations in different subregions of the medial prefrontal cortex (mPFC) of the precocious rodent degu (Octodon degus). At the age around puberty early stressed animals displayed significantly lower densities of calbindin-D28k-immunoreactive interneurons in the anterior cingulate (down to 79%) and in the precentral medial (down to 64%) subregions of the mPFC compared with age-matched unstressed controls. At this age the densities of two other interneuron types characterized by their expression of the calcium-binding proteins parvalbumin or calretinin remained at control levels. In adulthood, i.e. after an extended period without stress exposure, the density of calbindin-D28k-immunoreactive interneurons in the stressed animals was back to control numbers, whereas parvalbumin-immunoreactive interneurons displayed significantly elevated density in the anterior cingulate (up to 138%) and in the precentral medial cortex (up to 137%) of the stressed animals. In both age groups the density of calretinin- and corticotropin releasing hormone-immunoreactive interneurons did not differ between stressed and control animals, and the prelimbic and infralimbic subregions of the medial prefrontal cortex remained unaffected by stress experience. These results confirm that early adverse emotional experience induces long lasting age-, region- and neuron-specific imbalance of inhibitory systems in some, but not all subregions of the medial prefrontal cortex of the degu.

Heterogeneity of V2‐derived interneurons in the adult mouse spinal cord

Spinal neurons and networks that generate rhythmic locomotor activity remain incompletely defined, prompting the use of molecular biological strategies to label populations of neurons in the postnatal mouse. During spinal cord development, expression of Lhx3 in the absence of Isl1 specifies a V2 interneuronal fate. In this study, postnatal V2-derived interneurons were identified by yellow fluorescent protein (YFP) expression in the double-transgenic offspring of Lhx3Cre/+ x thy1-loxP-stop-loxP-YFP mice. While some motoneurons were labelled, several populations of interneurons predominantly located in lamina VII could also be distinguished. Small interneurons were located throughout the spinal cord whereas larger interneurons were concentrated in the lumbar enlargement. Some V2-derived interneurons were propriospinal, with axons that bifurcated in the lateral funiculus. V2-derived interneurons gave rise to populations of both excitatory and inhibitory interneurons in approximately equal proportions, as demonstrated by in situ hybridization with VGLUT2 mRNA. Immunohistochemical studies revealed YFP+ boutons throughout the spinal cord. Both glutamatergic and glycinergic YFP+ boutons were observed in lamina IX where many apposed motoneuron somata. GABAergic YFP+ boutons were also observed in lamina IX, and they did not form P-boutons. At P0, more than half of the YFP+ interneurons expressed Chx10 and thus were derived from the V2a subclass. In adult mice, there was an increase in Fos expression in V2-derived interneurons following locomotion, indicating that these neurons are active during this behaviour. The heterogeneity of V2-derived interneurons in adult mice indicates that physiologically distinct subpopulations, including last-order interneurons, arise from these embryonically defined neurons.

Intracortical circuits modulate transcallosal inhibition in humans

Previous results using paired-pulse transcranial magnetic stimulation (TMS) have suggested that the excitability of transcallosal (TC) connections between the hand areas of the two motor cortices is modulated by intracortical inhibitory circuits in the same way as corticospinal tract (CTS) projections to spinal motoneurons. Here we describe two further similarities in TC and CTS control using (1) an I-wave facilitation protocol and (2) preconditioning with rTMS. In experiment 1, excitability of TC pathways was measured using interhemispheric inhibition (IHI) and the ipsilateral silent period (iSP), whilst excitability of CTS pathways was measured by recording the EMG response evoked in the first dorsal interosseous muscle contralateral to the conditioning stimulus (cMEP). The intensity of the conditioning stimulus was first adjusted to threshold for evoking IHI and iSP, then pairs of conditioning stimuli were applied randomly at interstimulus intervals (ISIs) from 1.3 to 4.3 ms. IHI and iSP were facilitated at ISI=1.5 ms and 3.0 ms, respectively, as was the MEP evoked by the conditioning stimuli in the contralateral hand. We suggest that TC projections receive I-wave-like facilitation similar to that seen in CTS projections. In experiment 2, short interval inhibition of the iSP (SICIiSP), and short interval intracortical inhibition of the cMEP (SICIcMEP) were examined before and after 600 pulses of 5 Hz rTMS at 90% resting motor threshold. Both SICIiSP and SICIcMEP were reduced, as was the iSP; the cMEP was unchanged. This shows that the population of inhibitory interneurons that control TC neurons respond in the same way to 5 Hz rTMS as those that control CTS neurons. Taken together, the data from the two experiments suggest that the layer III and layer V pyramidal neurons that give rise to TC and CTS pathways, respectively, are controlled by neuronal circuitry with similar properties.

The kinetics of the IPSC, the heterogeneity and the noise affect the firing coherence of a population of inhibitory interneurons

The Fast Spiking interneurons are coupled by both inhibitory and electrical synapses and the experimental findings suggest they operate as clockworks affecting the neural information processing. At present, the functional role of the electrical synapses in a network of inhibitory interneurons is not well understood. In this paper, this issue is investigated by using a single compartment biophysical interneuron model of a Fast Spiking cell. In particular, the parameter values leading to the emergence of synchronous regimes in a network model of inhibitory interneurons coupled by chemical and electrical synapses are determined theoretically in the weak-coupling limit. Moreover, the effects on the firing coherence, arising from heterogeneity and noise, are studied by means of numerical simulations, both for a pair of Fast Spiking cells and for larger size networks.

HVC interneurons are not renewed in adult male zebra finches

Adult neurogenesis is a widespread phenomenon in many species, from invertebrates to humans. In songbirds, the telencephalic region, high vocal center (HVC), continuously integrates new neurons in adulthood. This nucleus consists of a heterogenous population of inhibitory interneurons (HVC(IN)) and two populations of projection neurons that send axons towards either the robust nucleus of the arcopallium (HVC(RA)) or the striatal nucleus area X (HVC(X)). New HVC neurons were initially inferred to be interneurons, because they lacked retrograde labelling from the HVC's targets. Later studies using different tracers demonstrated that HVC(RA) are replaced but HVC(X) are not. Whether interneurons are also renewed became an open question. As the HVC's neuronal populations display different physiological properties and functions, we asked whether adult HVC indeed recruits two neuronal populations or whether only the HVC(RA) undergo renewal in adult male zebra finches. We show that one month after being born in the lateral ventricle, 42% of the newborn HVC neurons were retrogradely labelled by tracer injections into the RA. However, the remaining 58% were not immunoreactive for the neurotransmitter GABA, nor for the calcium-binding proteins, parvalbumin (PA), calbindin (CB) and calretinin (CR) that characterize different classes of HVC(IN). We further established that simultaneous application of parvalbumin, calbindin and calretinin antibodies to HVC revealed approximately the same fraction of HVC neurons, i.e. 10%, as could be detected by GABA immunoreactivity. This implies that the sum of HVC(IN) expressing the different calcium-binding proteins constitute all inhibitory HVC(IN). Together these results strongly suggest that only HVC(RA) are recruited into the adult HVC.

GABAergic Input onto CA3 Hippocampal Interneurons Remains Shunting throughout Development

In hippocampus, the net flow of excitability is controlled by inhibitory input provided by the many populations of local circuit inhibitory interneurons. In principal cells, GABA(A) receptor-mediated synaptic input undergoes a highly coordinated shift from depolarizing early in life to a more conventional hyperpolarizing inhibition on maturation. This switch in inhibitory input polarity is controlled by the developmental regulation of two chloride cotransporters (NKCC1 and KCC2) that results in a net shift from high to low intracellular Cl(-). Whether inhibitory input onto inhibitory interneurons demonstrates a similar developmental shift in intracellular Cl(-) is unexplored. Using the gramicidin perforated-patch configuration, we recorded from CA3 hippocampal stratum lucidum interneurons and pyramidal cells to monitor inhibitory input across a broad developmental range. GABA(A) receptor-mediated synaptic input onto stratum lucidum inhibitory interneurons was shunting in nature across the entire developmental age range tested, as resting membrane potential and the IPSC reversal potential remained within a few millivolts (1-4 mV) between postnatal day 5 (P5) and P31. Furthermore, sensitivity to block of the two chloride cotransporters KCC2 and NKCC1 did not differ across the same age range, suggesting that their relative expression is fixed across development. In contrast, pyramidal cell synaptic inhibition demonstrated the well described switch from depolarizing to hyperpolarizing over the same age range. Thus, in contrast to principal cells, inhibitory synaptic input onto CA3 interneurons remains shunting throughout development.

Global rhythmic activities in hippocampal neural fields and neural coding

Global oscillations of the neural field represent some of the most interesting expressions of the hippocampal activity, being related also to learning and memory. To study oscillatory activities of the CA3 field in theta range, a model of this sub-field of Hippocampus has been formulated. The model describes the firing activity of CA3 neuronal populations within the frame of a kinetic theory of neural systems and it has been used for computer simulations. The results show that the propagation of activities induced in the neural field by hippocampal afferents occurs only in narrow time windows confined by inhibitory barrages, whose time-course follows the theta rhythm. Moreover, during each period of a theta wave, the entire CA3 field bears a firing activity with peculiar space–time patterns, a sort of specific i mprint, which can induce effects with similar patterns on brain regions driven by the hippocampal formation. The simulation has also demonstrated the ability of medial septum to influence the global activity of the CA3 pyramidal population through the control of the population of inhibitory interneurons. At last, the possible involvement of global population oscillations in neural coding has been discussed.