Somatic Membrane Research Articles

Tetrodotoxin abruptly blocks excitatory neurotransmission in mammalian CNS

The present study utilised a 'synaptic bouton' preparation of mechanically isolated rat hippocampal CA3 pyramidal neurons, which permits direct physiological and pharmacological quantitative analyses at the excitatory and inhibitory single synapse level. Evoked excitatory and inhibitory postsynaptic currents (eEPSCs and eIPSCs) were generated by focal paired-pulse electrical stimulation of single boutons. The sensitivity of eEPSC to tetrodotoxin (TTX) was higher than that of the voltage-dependent Na(+) channel whole-cell current (INa) in the postsynaptic CA3 soma membrane. The synaptic transmission was strongly inhibited by 3 nM TTX, at which concentration the INa was hardly suppressed. The IC50 values of eEPSC and INa for TTX were 2.8 and 37.9 nM, respectively, and complete inhibition was 3-10 nM for eEPSC and 1000 nM for INa. On the other hand, both eEPSC and eIPSC were equally and gradually inhibited by decreasing the external Na(+) concentration ([Na]o), which decreases the Na(+)gradient across the cell membrane. The results indicate that TTX at 3-10 nM could block most of voltage-dependent Na(+) channels on presynaptic nerve terminal, resulting in abruptly inhibition of action potential dependent excitatory neurotransmission.

Opinion: Presumable Reason of Interrelationship between Autoimmune Hemolytic Anemia and Cancer Arising

The mechanism of malignant transformation in autoimmune hemolytic anemia can be based on the inclusion of immunocompetent cells in different cellular cooperations. Antibodies and T-cytotoxic cells can induce perforations of different degree on somatic cells plasma membranes. Total negative charge of plasma membranes decrease, and the cells acquire the capability of closely approaching, which frequently, especially upon coincidence of the perforated parts, may serve as a prerequisite to fusion process and formation of cancerous cell.

Persistent discharges in dentate gyrus perisoma-inhibiting interneurons require hyperpolarization-activated cyclic nucleotide-gated channel activation.

Parvalbumin (PV)-expressing perisoma-inhibiting interneurons (PIIs) of the dentate gyrus integrate rapidly correlated synaptic inputs and generate short-duration action potentials that propagate along the axon to their output synapses, supporting fast inhibitory signaling onto their target cells. Here we show that PV-PIIs in rat and mouse dentate gyrus (DG) integrate their intrinsic activity over time and can turn into a persistent firing mode characterized by the ability to generate long-lasting trains of action potentials at ∼50 Hz in the absence of additional inputs. Persistent firing emerges in the axons remote from the axon initial segment and markedly depends on hyperpolarization-activated cyclic nucleotide-gated channel (HCNC) activation. Persistent firing properties are modulated by intracellular Ca(2+) levels and somatic membrane potential. Detailed computational single-cell PIIs models reveal that HCNC-mediated conductances can contribute to persistent firing during conditions of a shift in their voltage activation curve to more depolarized potentials. Paired recordings from PIIs and their target granule cells show that persistent firing supports strong inhibitory output signaling. Thus, persistent firing may emerge during conditions of intense activation of the network, thereby providing silencing to the circuitry and the maintenance of sparse activity in the dentate gyrus.

Power laws from linear neuronal cable theory: power spectral densities of the soma potential, soma membrane current and single-neuron contribution to the EEG.

Power laws, that is, power spectral densities (PSDs) exhibiting behavior for large frequencies f, have been observed both in microscopic (neural membrane potentials and currents) and macroscopic (electroencephalography; EEG) recordings. While complex network behavior has been suggested to be at the root of this phenomenon, we here demonstrate a possible origin of such power laws in the biophysical properties of single neurons described by the standard cable equation. Taking advantage of the analytical tractability of the so called ball and stick neuron model, we derive general expressions for the PSD transfer functions for a set of measures of neuronal activity: the soma membrane current, the current-dipole moment (corresponding to the single-neuron EEG contribution), and the soma membrane potential. These PSD transfer functions relate the PSDs of the respective measurements to the PSDs of the noisy input currents. With homogeneously distributed input currents across the neuronal membrane we find that all PSD transfer functions express asymptotic high-frequency power laws with power-law exponents analytically identified as for the soma membrane current, for the current-dipole moment, and for the soma membrane potential. Comparison with available data suggests that the apparent power laws observed in the high-frequency end of the PSD spectra may stem from uncorrelated current sources which are homogeneously distributed across the neural membranes and themselves exhibit pink () noise distributions. While the PSD noise spectra at low frequencies may be dominated by synaptic noise, our findings suggest that the high-frequency power laws may originate in noise from intrinsic ion channels. The significance of this finding goes beyond neuroscience as it demonstrates how power laws with a wide range of values for the power-law exponent α may arise from a simple, linear partial differential equation.

The Role of Myosins in Depression of Neuron Sensitivity to Acetylcholine in a Cellular Analog of Habituation in the Common Snail

The involvement of cytoskeletal motor proteins, i.e., myosins, in the molecular mechanism of depression of the acetylcholine sensitivity of defensive behavior command neurons was studied in the common snail. Thus, the effects of compounds impairing myosin functioning on ACh-evoked current depression curves in neurons were studied – the myosin light chain kinase blockers ML-7 and MLCK-IP-18, the non-muscle myosin II inhibitor blebbistatin, and the ROCK-I and ROCK-II kinase (which mainly activate non-muscle myosin II) inhibitor Y-27632. ML-7 and MLCK-IP-18 were found to weaken depression of the current, while blebbistatin and Y-27632 had no effect on depression. The experimental results and mathematical models of the effects of these blockers on the number of membrane-bound cholinoreceptors suggest the involvement of myosins (except non-muscle myosin II) in the endo- and exocytosis of cholinoreceptors and the resultant depression of the cholinosensitivity of the somatic membranes of neurons in a cellular analog of habituation.

Control of somatic membrane potential in nociceptive neurons and its implications for peripheral nociceptive transmission

Peripheral sensory ganglia contain somata of afferent fibres conveying somatosensory inputs to the central nervous system. Growing evidence suggests that the somatic/perisomatic region of sensory neurons can influence peripheral sensory transmission. Control of resting membrane potential (Erest) is an important mechanism regulating excitability, but surprisingly little is known about how Erest is regulated in sensory neuron somata or how changes in somatic/perisomatic Erest affect peripheral sensory transmission. We first evaluated the influence of several major ion channels on Erest in cultured small-diameter, mostly capsaicin-sensitive (presumed nociceptive) dorsal root ganglion (DRG) neurons. The strongest and most prevalent effect on Erest was achieved by modulating M channels, K2P and 4-aminopiridine-sensitive KV channels, while hyperpolarization-activated cyclic nucleotide-gated, voltage-gated Na+, and T-type Ca2+ channels to a lesser extent also contributed to Erest. Second, we investigated how varying somatic/perisomatic membrane potential, by manipulating ion channels of sensory neurons within the DRG, affected peripheral nociceptive transmission in vivo. Acute focal application of M or KATP channel enhancers or a hyperpolarization-activated cyclic nucleotide-gated channel blocker to L5 DRG in vivo significantly alleviated pain induced by hind paw injection of bradykinin. Finally, we show with computational modelling how somatic/perisomatic hyperpolarization, in concert with the low-pass filtering properties of the t-junction within the DRG, can interfere with action potential propagation. Our study deciphers a complement of ion channels that sets the somatic Erest of nociceptive neurons and provides strong evidence for a robust filtering role of the somatic and perisomatic compartments of peripheral nociceptive neuron.

Optical imaging of neuronal activity and visualization of fine neural structures in non-desheathed nervous systems.

Locating circuit neurons and recording from them with single-cell resolution is a prerequisite for studying neural circuits. Determining neuron location can be challenging even in small nervous systems because neurons are densely packed, found in different layers, and are often covered by ganglion and nerve sheaths that impede access for recording electrodes and neuronal markers. We revisited the voltage-sensitive dye RH795 for its ability to stain and record neurons through the ganglion sheath. Bath-application of RH795 stained neuronal membranes in cricket, earthworm and crab ganglia without removing the ganglion sheath, revealing neuron cell body locations in different ganglion layers. Using the pyloric and gastric mill central pattern generating neurons in the stomatogastric ganglion (STG) of the crab, Cancer borealis, we found that RH795 permeated the ganglion without major residue in the sheath and brightly stained somatic, axonal and dendritic membranes. Visibility improved significantly in comparison to unstained ganglia, allowing the identification of somata location and number of most STG neurons. RH795 also stained axons and varicosities in non-desheathed nerves, and it revealed the location of sensory cell bodies in peripheral nerves. Importantly, the spike activity of the sensory neuron AGR, which influences the STG motor patterns, remained unaffected by RH795, while desheathing caused significant changes in AGR activity. With respect to recording neural activity, RH795 allowed us to optically record membrane potential changes of sub-sheath neuronal membranes without impairing sensory activity. The signal-to-noise ratio was comparable with that previously observed in desheathed preparations and sufficiently high to identify neurons in single-sweep recordings and synaptic events after spike-triggered averaging. In conclusion, RH795 enabled staining and optical recording of neurons through the ganglion sheath and is therefore both a good anatomical marker for living neural tissue and a promising tool for studying neural activity of an entire network with single-cell resolution.

Cell type-specific spatial and functional coupling between mammalian brain Kv2.1 K+ channels and ryanodine receptors.

The Kv2.1 voltage-gated K+ channel is widely expressed throughout mammalian brain, where it contributes to dynamic activity-dependent regulation of intrinsic neuronal excitability. Here we show that somatic plasma membrane Kv2.1 clusters are juxtaposed to clusters of intracellular ryanodine receptor (RyR) Ca2+ -release channels in mouse brain neurons, most prominently in medium spiny neurons (MSNs) of the striatum. Electron microscopy-immunogold labeling shows that in MSNs, plasma membrane Kv2.1 clusters are adjacent to subsurface cisternae, placing Kv2.1 in close proximity to sites of RyR-mediated Ca2+ release. Immunofluorescence labeling in transgenic mice expressing green fluorescent protein in specific MSN populations reveals the most prominent juxtaposed Kv2.1:RyR clusters in indirect pathway MSNs. Kv2.1 in both direct and indirect pathway MSNs exhibits markedly lower levels of labeling with phosphospecific antibodies directed against the S453, S563, and S603 phosphorylation site compared with levels observed in neocortical neurons, although labeling for Kv2.1 phosphorylation at S563 was significantly lower in indirect pathway MSNs compared with those in the direct pathway. Finally, acute stimulation of RyRs in heterologous cells causes a rapid hyperpolarizing shift in the voltage dependence of activation of Kv2.1, typical of Ca2+ /calcineurin-dependent Kv2.1 dephosphorylation. Together, these studies reveal that striatal MSNs are distinct in their expression of clustered Kv2.1 at plasma membrane sites juxtaposed to intracellular RyRs, as well as in Kv2.1 phosphorylation state. Differences in Kv2.1 expression and phosphorylation between MSNs in direct and indirect pathways provide a cell- and circuit-specific mechanism for coupling intracellular Ca2+ release to phosphorylation-dependent regulation of Kv2.1 to dynamically impact intrinsic excitability.

Calcium current improves coincidence detection of the LIF model

Dendritic spikes are known to improve efficacy of synaptic inputs in causing action potentials [1]. The calcium spike at distal apical dendrites of layer 5 pyramidal neurons has been observed in-vitro and argued to support the propagation of synaptic inputs from distal tufts to the soma [2]. When combined with a back-propagating action potential, a smaller distal current is sufficient to trigger a calcium spike [3]. Recently, it has also been shown in-vivo that dendritic spikes contribute to the neuronal activity [4,5]. Calcium spikes have been modeled in multi-compartment point neuron models using first order kinetics [6]. Here we show that calcium spikes, in the regime of large synchronous inputs on top of a background of weakly fluctuating synaptic noise can be well approximated by a threshold-triggered current of fixed waveform. The exact contribution of the calcium spike to the somatic membrane potential can then be analytically derived. Accurate predictions are only obtained if correlations between the membrane potential and synaptic conductances are taken into account [7]. Comparing neuron models with and without calcium dynamics, we find that the calcium current increases the sensitivity of the neuron's spiking response to sufficiently large coincident input. In numerical simulations carried out with NEST [8], we investigate the effect of the jitter of close to synchronous inputs on the probability to elicit a calcium spike. With increased jitter, fewer calcium spikes are elicited and their average amplitude decreases.

Up-regulation of matrix metallopeptidase 12 in motor neurons undergoing synaptic stripping

Axotomy of the rodent facial nerve represents a well-established model of synaptic plasticity. Post-traumatic “synaptic stripping” was originally discovered in this system. We report upregulation of matrix metalloproteinase MMP12 in regenerating motor neurons of the mouse and rat facial nucleus. Matrix metalloproteinases (matrix metallopeptidases, MMPs) are zinc-binding proteases capable of degrading components of the extracellular matrix and of regulating extracellular signaling networks including within synapses. MMP12 protein expression in facial motor neurons was enhanced following axotomy and peaked at day 3 after the operation. The peak of neuronal MMP12 expression preceded the peak of experimentally induced synaptic plasticity. At the same time, MMP12 redistributed intracellularly and became predominantly localized beneath the neuronal somatic cytoplasmic membrane. Both findings point to a role of MMP12 in the neuronal initiation of the synaptic stripping process. MMP12 is the first candidate molecule for such a trigger function and has potential as a therapeutic target. Moreover, since statins have been shown to increase the expression of MMP12, interference with synaptic stability may represent one mechanism by which these widely used drugs exert their side effects on higher CNS functions.

Neuronal spike initiation modulated by extracellular electric fields.

Based on a reduced two-compartment model, the dynamical and biophysical mechanism underlying the spike initiation of the neuron to extracellular electric fields is investigated in this paper. With stability and phase plane analysis, we first investigate in detail the dynamical properties of neuronal spike initiation induced by geometric parameter and internal coupling conductance. The geometric parameter is the ratio between soma area and total membrane area, which describes the proportion of area occupied by somatic chamber. It is found that varying it could qualitatively alter the bifurcation structures of equilibrium as well as neuronal phase portraits, which remain unchanged when varying internal coupling conductance. By analyzing the activating properties of somatic membrane currents at subthreshold potentials, we explore the relevant biophysical basis of spike initiation dynamics induced by these two parameters. It is observed that increasing geometric parameter could greatly decrease the intensity of the internal current flowing from soma to dendrite, which switches spike initiation dynamics from Hopf bifurcation to SNIC bifurcation; increasing internal coupling conductance could lead to the increase of this outward internal current, whereas the increasing range is so small that it could not qualitatively alter the spike initiation dynamics. These results highlight that neuronal geometric parameter is a crucial factor in determining the spike initiation dynamics to electric fields. The finding is useful to interpret the functional significance of neuronal biophysical properties in their encoding dynamics, which could contribute to uncovering how neuron encodes electric field signals.

Distinct axo-somato-dendritic distributions of three potassium channels in CA1 hippocampal pyramidal cells.

Potassium channels comprise the most diverse family of ion channels and play critical roles in a large variety of physiological and pathological processes. In addition to their molecular diversity, variations in their distributions and densities on the axo-somato-dendritic surface of neurons are key parameters in determining their functional impact. Despite extensive electrophysiological and anatomical investigations, the exact location and densities of most K+ channels in small subcellular compartments are still unknown. Here we aimed at providing a quantitative surface map of two delayed-rectifier (Kv1.1 and Kv2.1) and one G-protein-gated inwardly rectifying (Kir3.2) K+ channel subunits on hippocampal CA1 pyramidal cells (PCs). Freeze-fracture replica immunogold labelling was employed to determine the relative densities of these K+ channel subunits in 18 axo-somato-dendritic compartments. Significant densities of the Kv1.1 subunit were detected on axon initial segments (AISs) and axon terminals, with an approximately eight-fold lower density in the latter compartment. The Kv2.1 subunit was found in somatic, proximal dendritic and AIS plasma membranes at approximately the same densities. This subunit has a non-uniform plasma membrane distribution; Kv2.1 clusters are frequently adjacent to, but never overlap with, GABAergic synapses. A quasi-linear increase in the Kir3.2 subunit density along the dendrites of PCs was detected, showing no significant difference between apical dendritic shafts, oblique dendrites or dendritic spines at the same distance from the soma. Our results demonstrate that each subunit has a unique cell-surface distribution pattern, and predict their differential involvement in synaptic integration and output generation at distinct subcellular compartments.

Regulation of SK Channel Spatial Distribution by Tonic PKA

Introduction: Small-conductance Ca2+-activated K+ (SK) channels mediate a ubiquitous expressed potassium conductance in the brain involved in synaptic plasticity and learning and memory. SK channel spatial distribution shows a polarized topographic expression being highly enriched in neuronal dendrites with limited expression on somatic membranes. However, the mechanism that controls this spatial distribution is unknown. To investigate the mechanisms that control the spatial distribution of SK channels at the single molecule level we combine single molecule atomic force microscopy and toxin pharmacology.Methods and results: AFM tip functionalized with apamin, a SK channel blocker, is used to detect the distribution of SK channels in living neurons by measuring the binding forces between apamin and SK channels. Employing the above technique, we test the effect of PKA on the clustering and dendritic localization of SK channels. Here, we show that SK2 channel nanoclustering is under the control of cAMP and PKA activity and demonstrate that SK2 channel polarized distribution in neurons is dictated by basal PKA activity.Conclusion: Our work reveals a new level of regulation of SK2 channels by PKA and also demonstrates for the first time that SK2 spatial distribution is plastic.

Allotransplantation and Its Association with Rising Incidence of Cancers

In some cases of allotransplantation, simultaneous development of malignant tumors of different histogenesis may be observed. We propose to consider malignant tumor formation during allotransplantations in terms of karyogamic theory of carcinogenesis. Experience in transplantology tentatively testify that even in cases of maximal antigen compatibility of donors and recipients, immune conflict is unavoidable. As we believe, in immunological conflict between recipient and donor cells, the process of cells’ destruction in some cases may be accompanied by damages of plasma membranes and somatic hybridization between immunocompetent cells of the recipient and any cell of transplanted donor’s tissue, which may lead to the emergence of a cancer cell. Antibodies and cytotoxic cells can induce damages (perforations) of different degree on somatic cells plasma membranes, which can represent firstly the precancerous and later the true cancerous cells formation.

Drinking-Related Tetrahydroharmans Counteract the Membrane Effects of Local Anesthetic Lidocaine

There is a general consensus in dentistry that successful local anesthesia is frequently difficult in habitual drinkers and alcoholic patients. Neuro-active tetrahydroharmans increase in human body fluids and tissues by consuming alcoholic beverages. To understand such reduced anesthetic efficacy by the drug interaction hypothesis, we studied the influences of drinking-related tetrahydroharmans on membrane fluidization as one of local anesthetic mechanisms. Lipo- somal membranes prepared with phosphatidylcholine and cholesterol were treated with lidocaine and different tetrahydroharmans separately and in combination, followed by measuring fluorescence polarization to determine their induced changes in membrane fluidity. In contrast to 0.1-2 mg/mL lidocaine, tetrahydroharmans decreased the fluidity of membrane preparations at ∼ 25 μg/mL with the potency being

Non-linear dendrites can tune neurons

Event Abstract Back to Event Non-linear dendrites can tune neurons Romain D. Cazé1* and Simon R. Schultz1 1 Imperial College London, Department of Bioengineering, United Kingdom A signature of visual, auditory, and motor cortices is the presence of neurons tuned to distinct features of the environment. While neuronal tuning can be observed in most brain areas, its origin remains enigmatic, and new calcium imaging data complicate this problem. Dendritic calcium signals, in a L2/3 neuron from the mouse visual cortex, display a wide range of tunings that could be different from the neuronal tuning (Jia et al 2010). To elucidate this observation we use multi-compartmental models of increasing complexity, from a binary to a realistic biophysical model of L2/3 neuron. These models possess non-linear dendritic subunits inside which the result of multiple excitatory inputs is smaller than their arithmetic sum. While dendritic non-linear subunits are ad-hoc in the binary model, non-linearities in the realistic model come from the passive saturation of synaptic currents. Because of these non-linearities our neuron models are scatter sensitive: the somatic membrane voltage is higher when presynaptic inputs target different dendrites than when they target a single dendrite. This spatial bias in synaptic integration is, in our models, the origin of neuronal tuning. Indeed, assemblies of presynaptic inputs encode the stimulus property through an increase in correlation or activity, and only the assembly that encodes the preferred stimulus targets different dendrites. Assemblies coding for the non-preferred stimuli target single dendrites, explaining the wide range of observed tunings and the possible difference between dendritic and somatic tuning. We thus propose, in accordance with the latest experimental observations, that non-linear integration in dendrites can generate neuronal tuning independently of the coding regime. References Jia, Hongbo, Nathalie L. Rochefort, Xiaowei Chen, and Arthur Konnerth. 2010. “Dendritic Organization of Sensory Input to Cortical Neurons in Vivo.” Nature 464 (7293): 1307–1312. Keywords: dendritic computation, Neuronal Tuning, Dendrites, computational neuroscience, single neuron computation Conference: 4th NAMASEN Training Workshop - Dendrites 2014, Heraklion, Greece, 1 Jul - 4 Jul, 2014. Presentation Type: Oral presentation Topic: the role of dendrites in complex processes, including learning/memory and neural computations Citation: Cazé RD and Schultz SR (2014). Non-linear dendrites can tune neurons. Front. Syst. Neurosci. Conference Abstract: 4th NAMASEN Training Workshop - Dendrites 2014. doi: 10.3389/conf.fnsys.2014.05.00043 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: 11 Apr 2014; Published Online: 12 Jun 2014. * Correspondence: Dr. Romain D Cazé, Imperial College London, Department of Bioengineering, London, SW7 2AZ, United Kingdom, r.caze@imperial.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 Romain D Cazé Simon R Schultz Google Romain D Cazé Simon R Schultz Google Scholar Romain D Cazé Simon R Schultz PubMed Romain D Cazé Simon R Schultz 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.

C-terminal region of teneurin-1 co-localizes with the dystroglycan complex in adult mouse testes and regulates testicular size and testosterone production

Testicular size is directly proportional to fertility potential and is dependent on the integration of developmental proteins, trophic factors, and sex steroids. The teneurins are transmembrane glycoproteins that function as signaling and cell adhesion molecules in the establishment and maintenance of the somatic gonad, gametogenesis, and basement membrane. Moreover, teneurins are thought to function redundantly to the extracellular matrix protein, dystroglycan. Encoded on the last exon of the teneurin genes is a family of bioactive peptides termed the teneurin C-terminal-associated peptides (TCAPs). One of these peptides, TCAP-1, functionally interacts with β-dystroglycan to act as a neuromodulatory peptide with trophic characteristics independent from the teneurins. However, little is known about the localization and relationship between the teneurin-TCAP-1 system and the dystroglycans in the gonad. In the adult mouse testis, immunoreactive TCAP-1 was localized to spermatogonia and spermatocytes and co-localized with β-dystroglycan. However, teneurin-1 was localized to the peritubular myoid cell layer of seminiferous tubules and tubules within the epididymis, and co-localized with α-dystroglycan and α-smooth muscle actin. TCAP-1-binding sites were identified in the germ cell layers and adluminal compartment of the seminiferous tubules, and epithelial cells of the epididymis. In vivo, TCAP-1 administration to adult mice for 9days increased testicular size, seminiferous and epididymal tubule short-diameter and elevated testosterone levels. TCAP-1-treated mice also showed increased TCAP-1 immunoreactivity in the caput and corpa epididymis. Our data provide novel evidence of TCAP-1 localization in the testes that is distinct from teneurin-1, but is integrated through an association with the dystroglycan complex.

Learning-Related Translocation of δ-Opioid Receptors on Ventral Striatal Cholinergic Interneurons Mediates Choice between Goal-Directed Actions

The ability of animals to extract predictive information from the environment to inform their future actions is a critical component of decision-making. This phenomenon is studied in the laboratory using the pavlovian-instrumental transfer protocol in which a stimulus predicting a specific pavlovian outcome biases choice toward those actions earning the predicted outcome. It is well established that this transfer effect is mediated by corticolimbic afferents on the nucleus accumbens shell (NAc-S), and recent evidence suggests that δ-opioid receptors (DORs) play an essential role in this effect. In DOR-eGFP knock-in mice, we show a persistent, learning-related plasticity in the translocation of DORs to the somatic plasma membrane of cholinergic interneurons (CINs) in the NAc-S during the encoding of the specific stimulus-outcome associations essential for pavlovian-instrumental transfer. We found that increased membrane DOR expression reflected both stimulus-based predictions of reward and the degree to which these stimuli biased choice during the pavlovian-instrumental transfer test. Furthermore, this plasticity altered the firing pattern of CINs increasing the variance of action potential activity, an effect that was exaggerated by DOR stimulation. The relationship between the induction of membrane DOR expression in CINs and both pavlovian conditioning and pavlovian-instrumental transfer provides a highly specific function for DOR-related modulation in the NAc-S, and it is consistent with an emerging role for striatal CIN activity in the processing of predictive information. Therefore, our results reveal evidence of a long-term, experience-dependent plasticity in opioid receptor expression on striatal modulatory interneurons critical for the cognitive control of action.

Polarized distribution of AMPA, but not GABAA, receptors in radial glia‐like cells of the adult dentate gyrus

Glial fibrillary acidic protein (GFAP)-positive astrocytes with radial processes [radial glia (RG)-like cells] in the postnatal dentate gyrus share many of the characteristics of embryonic radial glia and appear to act as precursor cells for adult dentate neurogenesis, a process important for pattern separation and hippocampus-dependent learning. Although much work has delineated the mechanisms underlying activity-neurogenesis coupling via gamma-amino butyric acid (GABA)ergic neurotransmission on GFAP-negative transient-amplifying cells and neuroblasts, little is known regarding the effects of neurotransmitters on RG-like cells. Conflicting evidence exists for both GABA and glutamate receptors on these cells. Here, using GFAP reporter mice, we show that the somatic membrane of RG-like cells carries GABAA receptors and glutamate transporters but not ionotropic glutamate receptors, whereas 2-amino-3-(hydroxyl-5-methylisoxazole-4-yl) propionic acid (AMPA) and GABAA receptors are expressed on the processes of these cells. Almost all RG-like cells expressed the GluA2 subunit, which restricts the Ca(2+) permeability of AMPA receptors. The glial GABAA receptors mainly comprised α2/α4, β1, and γ1/γ3. The selective presence of AMPA receptors on the radial processes may be important for sensing and responding to local activity-driven glutamate release and supports the concept that RG-like astrocytes are composed of functional and structural domains.

The calcium-binding protein parvalbumin modulates the firing 1 properties of the reticular thalamic nucleus bursting neurons

The reticular thalamic nucleus (RTN) of the mouse is characterized by an overwhelming majority of GABAergic neurons receiving afferences from both the thalamus and the cerebral cortex and sending projections mainly on thalamocortical neurons. The RTN neurons express high levels of the "slow Ca(2+) buffer" parvalbumin (PV) and are characterized by low-threshold Ca(2+) currents, I(T). We performed extracellular recordings in ketamine/xylazine anesthetized mice in the rostromedial portion of the RTN. In the RTN of wild-type and PV knockout (PVKO) mice we distinguished four types of neurons characterized on the basis of their firing pattern: irregular firing (type I), medium bursting (type II), long bursting (type III), and tonically firing (type IV). Compared with wild-type mice, we observed in the PVKOs the medium bursting (type II) more frequently than the long bursting type and longer interspike intervals within the burst without affecting the number of spikes. This suggests that PV may affect the firing properties of RTN neurons via a mechanism associated with the kinetics of burst discharges. Ca(v)3.2 channels, which mediate the I(T) currents, were more localized to the somatic plasma membrane of RTN neurons in PVKO mice, whereas Ca(v)3.3 expression was similar in both genotypes. The immunoelectron microscopy analysis showed that Ca(v)3.2 channels were localized at active axosomatic synapses, thus suggesting that the differential localization of Ca(v)3.2 in the PVKOs may affect bursting dynamics. Cross-correlation analysis of simultaneously recorded neurons from the same electrode tip showed that about one-third of the cell pairs tended to fire synchronously in both genotypes, independent of PV expression. In summary, PV deficiency does not affect the functional connectivity between RTN neurons but affects the distribution of Ca(v)3.2 channels and the dynamics of burst discharges of RTN cells, which in turn regulate the activity in the thalamocortical circuit.