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Inhibitory Synapses (inhibitory + synapsis)
Selected AbstractsConsistent dynamics suggests tight regulation of biophysical parameters in a small network of bursting neuronsDEVELOPMENTAL NEUROBIOLOGY, Issue 14 2006Attila Szücs Abstract The neuronal firing patterns in the pyloric network of crustaceans are remarkably consistent among animals. Although this characteristic of the pyloric network is well-known, the biophysical mechanisms underlying the regulation of the systems output are receiving renewed attention. Computer simulations of the pyloric network recently demonstrated that consistent motor output can be achieved from neurons with disparate biophysical parameters among animals. Here we address this hypothesis by pharmacologically manipulating the pyloric network and analyzing the emerging voltage oscillations and firing patterns. Our results show that the pyloric network of the lobster stomatogastric ganglion maintains consistent and regular firing patterns even when entire populations of specific voltage-gated channels and synaptic receptors are blocked. The variations of temporal parameters used to characterize the burst patterns of the neurons as well as their intraburst spike dynamics do not display statistically significant increase after blocking the transient K-currents (with 4-aminopyridine), the glutamatergic inhibitory synapses (with picrotoxin), or the cholinergic synapses (with atropine) in pyloric networks from different animals. These data suggest that in this very compact circuit, the biophysical parameters are cell-specific and tightly regulated. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006 [source] A novel role for MNTB neuron dendrites in regulating action potential amplitude and cell excitability during repetitive firingEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2008Richardson N. Leão Abstract Principal cells of the medial nucleus of the trapezoid body (MNTB) are simple round neurons that receive a large excitatory synapse (the calyx of Held) and many small inhibitory synapses on the soma. Strangely, these neurons also possess one or two short tufted dendrites, whose function is unknown. Here we assess the role of these MNTB cell dendrites using patch-clamp recordings, imaging and immunohistochemistry techniques. Using outside-out patches and immunohistochemistry, we demonstrate the presence of dendritic Na+ channels. Current-clamp recordings show that tetrodotoxin applied onto dendrites impairs action potential (AP) firing. Using Na+ imaging, we show that the dendrite may serve to maintain AP amplitudes during high-frequency firing, as Na+ clearance in dendritic compartments is faster than axonal compartments. Prolonged high-frequency firing can diminish Na+ gradients in the axon while the dendritic gradient remains closer to resting conditions; therefore, the dendrite can provide additional inward current during prolonged firing. Using electron microscopy, we demonstrate that there are small excitatory synaptic boutons on dendrites. Multi-compartment MNTB cell simulations show that, with an active dendrite, dendritic excitatory postsynaptic currents (EPSCs) elicit delayed APs compared with calyceal EPSCs. Together with high- and low-threshold voltage-gated K+ currents, we suggest that the function of the MNTB dendrite is to improve high-fidelity firing, and our modelling results indicate that an active dendrite could contribute to a ,dual' firing mode for MNTB cells (an instantaneous response to calyceal inputs and a delayed response to non-calyceal dendritic excitatory postsynaptic potentials). [source] Synapse-specific localization of vesicular glutamate transporters in the rat olfactory bulbEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2007Marie-Madeleine Gabellec Abstract Vesicular glutamate transporters (VGLUTs) mediate the packaging of the excitatory neurotransmitter glutamate into synaptic vesicles. Three VGLUT subtypes have so far been identified, with distinct expression patterns in the adult brain. Here, we investigated the spatial distribution of the three VGLUTs in the rat olfactory bulb, a brain region containing a variety of glutamate synapses, both axodendritic and dendrodendritic. Using multilabelling confocal microscopy and electron microscopic immunocytochemistry, we showed that each VGLUT isoform has a highly selective localization in olfactory bulb synapses. VGLUT1 is present at dendrodendritic synapses established by the output neurones (mitral and tufted cells) with bulbar interneurones in the glomerular layer and external plexiform layer, as well as in axonal synapses of the granule cell layer. By contrast, VGLUT2 is strongly expressed in axon terminals of olfactory sensory neurones, which establish synapses with second-order neurones in the glomerular neuropil. VGLUT2 is also found in the outer part of the external plexiform layer and in the granule cell layer but colocalizes only partially with VGLUT1. Finally, we showed that VGLUT3 is exclusively located in the glomerular neuropil, where it colocalizes extensively with the vesicular inhibitory amino acid transporter vesicular GABA transporter, suggesting that it is associated with a subset of inhibitory synapses. Together, these observations extend previous findings on VGLUT distribution in the forebrain, and suggest that each VGLUT subtype has a specific function in the distinct features of axodendritic and dendrodendritic synapses that characterize the olfactory bulb circuit. [source] Enhanced synaptic excitation,inhibition ratio in hippocampal interneurons of rats with temporal lobe epilepsyEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2007F. Stief Abstract A common feature of all epileptic syndromes is the repetitive occurrence of pathological patterns of synchronous neuronal activity, usually combined with increased neuronal discharge rates. Inhibitory interneurons of the hippocampal formation control both neuronal synchronization as well as the global level of activity and are therefore of crucial importance for epilepsy. Recent evidence suggests that changes in synaptic inhibition during temporal lobe epilepsy are rather specific, resulting from selective death or alteration of interneurons in specific hippocampal layers. Hence, epilepsy-induced changes have to be analysed separately for different types of interneurons. Here, we focused on GABAergic neurons located at the border between stratum radiatum and stratum lacunosum-moleculare of hippocampal area CA1 (SRL interneurons), which are included in feedforward inhibitory circuits. In chronically epileptic rats at 6,8 months after pilocarpine-induced status epilepticus, frequencies of spontaneous and miniature inhibitory postsynaptic currents were reduced, yielding an almost three-fold increase in excitation,inhibition ratio. Consistently, action potential frequency of SRL interneurons was about two-fold enhanced. Morphological alterations of the interneurons indicate that these functional changes were accompanied by remodelling of the local network, probably resulting in a loss of functional inhibitory synapses without conceivable cell death. Our data indicate a strong increase in activity of interneurons in dendritic layers of the chronically epileptic CA1 region. This alteration may enhance feedforward inhibition and rhythmogenesis and , together with specific changes in other interneurons , contribute to seizure susceptibility and pathological synchronization. [source] Pre- and postsynaptic GABAA receptors at reciprocal dendrodendritic synapses in the olfactory bulbEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2004Patrizia Panzanelli Abstract Presynaptic ionotropic receptors are important regulators of synaptic function; however, little is known about their organization in the presynaptic membrane. We show here a different spatial organization of presynaptic and postsynaptic GABAA receptors at reciprocal dendrodendritic synapses between mitral and granule cells in the rat olfactory bulb. Using postembedding electron microscopy, we have found that mitral cell dendrites express GABAA receptors at postsynaptic specializations of symmetric (GABAergic) synapses, as well as at presynaptic sites of asymmetric (glutamatergic) synapses. Analysis of the subsynaptic distribution of gold particles revealed that in symmetric synapses GABAA receptors are distributed along the entire postsynaptic membrane, whereas in asymmetric synapses they are concentrated at the edge of the presynaptic specialization. To assess the specificity of immunogold labelling, we analysed the olfactory bulbs of mutant mice lacking the ,1 subunit of GABAA receptors. We found that in wild-type mice ,1 subunit immunoreactivity was similar to that observed in rats, whereas in knockout mice the immunolabelling was abolished. These results indicate that in mitral cell dendrites GABAA receptors are distributed in a perisynaptic domain that surrounds the presynaptic specialization. Such presynaptic receptors may be activated by spillover of GABA from adjacent inhibitory synapses and modulate glutamate release, thereby providing a novel mechanism regulating dendrodendritic inhibition in the olfactory bulb. [source] Quantitative effects produced by modifications of neuronal activity on the size of GABAA receptor clusters in hippocampal slice culturesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2004Serge Marty Abstract The number and strength of GABAergic synapses needs to be precisely adjusted for adequate control of excitatory activity. We investigated to what extent the size of GABAA receptor clusters at inhibitory synapses is under the regulation of neuronal activity. Slices from P7 rat hippocampus were cultured for 13 days in the presence of bicuculline or 4-aminopyridine (4-AP) to increase neuronal activity, or DNQX to decrease activity. The changes provoked by these treatments on clusters immunoreactive for the ,1 and ,2 subunits of the GABAA receptor or gephyrin were quantitatively evaluated. While an increase in activity augmented the density of these clusters, a decrease in activity provoked, in contrast, a decrease in their density. An inverse regulation was observed for the size of individual clusters. Bicuculline and 4-AP decreased whilst DNQX increased the mean size of the clusters. When the pharmacological treatments were applied for 2 days instead of 2 weeks, no effects on the size of the clusters were observed. The variations in the mean size of individual clusters were mainly due to changes in the number of small clusters. Finally, a regulation of the size of GABAA receptor clusters occurred during development in vivo, with a decrease of the mean size of the clusters between P7 and P21. This physiological change was also the result of an increase in the number of small clusters. These results indicate that neuronal activity regulates the mean size of GABAA receptor- and gephyrin-immunoreactive clusters by modifying specifically the number of synapses with small clusters of receptors. [source] Convergence of excitatory and inhibitory inputs onto CCK-containing basket cells in the CA1 area of the rat hippocampusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2004Ferenc Mátyás Abstract The number and distribution of excitatory and inhibitory inputs affect the integrative properties of neurons. These parameters have been studied recently for several hippocampal neuron populations. Besides parvalbumin- (PV) containing cells that include basket and axo-axonic cells, cholecystokinin (CCK)-containing interneurons also form a basket cell population with several properties distinct from PV cells. Here, at the light microscopic level, we reconstructed the entire dendritic tree of CCK-immunoreactive (IR) basket cells to describe their geometry, the total length and laminar distribution of their dendrites. This was followed by an electron microscopic analysis of serial ultrathin sections immunostained against ,-aminobutyric acid, to estimate the density of excitatory and inhibitory synapses on their somata, axon initial segments and different subclasses of dendrites. The dendritic tree of CCK-IR basket cells has an average length of 6300 µm and penetrates all layers. At the electron microscopic level, CCK basket cells receive dendritic inputs with a density of 80,230 per 100 µm. The ratio of inhibitory inputs is relatively high (35%) and increases towards the soma (83%). The total numbers of excitatory and inhibitory synapses converging onto CCK-IR cells are ,,8200. Comparison of the two, neurochemically distinct basket cells reveals that CCK-containing basket cells receive much less synaptic input than PV cells; however, the relative weight of inhibition is higher on CCK cells. Additional differences in their anatomical and physiological properties predict that CCK basket cells are under a more diverse, elaborate control than PV basket cells, and thus the function of the two populations must be different. [source] Activity-dependent modulation of GABAergic synapses in developing rat spinal networks in vitroEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2002Marcelo Rosato-Siri Abstract The role of activity-dependent plasticity in modulating inhibitory synapses was investigated in embryonic rat spinal cord slice cultures, by chronic exposure to non-NMDA receptor blockers. GABAergic synaptic efficacy in control and chronic-treated cultures was investigated by patch-recordings from visually identified spinal interneurons. In both culture groups proximal stimulation induced the appearance of postsynaptic currents (PSCs), which were fully antagonized by 20 µM bicuculline application and reverse polarity at potential values close to those reported for spontaneous GABAergic PSCs. In chronically treated cells GABAergic evoked PSCs displayed a larger failure rate and a smaller coefficient of variation of mean PSC amplitude, when compared to controls. As opposed to controls, chronic GABAergic evoked PSCs did not facilitate upon paired-pulse stimulation. Facilitation at chronic synapses was observed when extracellular calcium levels were decreased below physiological values (< 2 mM). Kainate was used to disclose any functional differences between control and treated slices. In accordance with the presynaptic action of kainate, the application of this drug along with GYKI, an AMPA receptor selective antagonist, changed, with analogous potency, short-term plasticity of GABAergic synapses from control and treated cultures. Nevertheless, in chronic cultures, the downstream effects of such activation unmasked short-term depression. Ultrastructural analysis of synapses in chronically treated cultures showed a reduction both in symmetric synapses and in the number of vesicles at symmetric terminals. Thus, based on electrophysiological and ultrastructural data, it could be suggested that during the development of spinal circuits, GABAergic synapses are modulated by glutamatergic transmission, and thus implying that excitatory transmission regulates the strength of GABAergic synapses. [source] Hormonal enhancement of neuronal firing is linked to structural remodelling of excitatory and inhibitory synapsesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2002A. Parducz Abstract The ovarian hormone estradiol induces morphological changes in the number of synaptic inputs in specific neuronal populations. However, the functional significance of these changes is still unclear. In this study, the effect of estradiol on the number of anatomically identified synaptic inputs has been assessed in the hypothalamic arcuate nucleus. The number of axo-somatic, axodendritic and spine synapses was evaluted using unbiased stereological methods and a parallel electrophysiological study was performed to assess whether synaptic anatomical remodelling has a functional consequence on the activity of the affected neurons. Estradiol administration to ovariectomized rats induced a decrease in the number of inhibitory synaptic inputs, an increase in the number of excitatory synapses and an enhancement of the frequency of neuronal firing. These results indicate that oestrogen modifications in firing frequency in arcuate neurons are temporally linked to anatomical modifications in the numerical balance of inhibitory and excitatory synaptic inputs. [source] Postnatal maturation of Na+, K+, 2Cl, cotransporter expression and inhibitory synaptogenesis in the rat hippocampus: an immunocytochemical analysisEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2002Serge Marty Abstract GABA, a major inhibitory neurotransmitter, depolarizes hippocampal pyramidal neurons during the first postnatal week. These depolarizations result from an efflux of Cl, through GABAA -gated anion channels. The outward Cl, gradient that provides the driving force for Cl, efflux might be generated and maintained by the Na+, K+, 2Cl, cotransporter (NKCC) that keeps intracellular Cl, concentration above electrochemical equilibrium. The developmental pattern of expression of the cotransporter in the hippocampus is not known. We studied the postnatal distribution pattern of NKCC in the hippocampus using a monoclonal antibody (T4) against a conserved epitope in the C-terminus of the cotransporter molecule. We also examined the temporal relationships between the developmental pattern of NKCC expression and the formation of perisomatic GABAergic synapses. This study was aimed at determining, with antivesicular inhibitory amino acid transporter (VIAAT) antibodies, whether perisomatic GABAergic synapses are formed preferentially at the time when GABA is depolarizing. During the first postnatal week, NKCC immunolabelling was restricted to cell bodies in the pyramidal cell layer and in the strata oriens and radiatum. In contrast, at postnatal day 21 (P21) and in adult animals little or no labelling occurred in cell bodies; instead, a prominent dendritic labelling appeared in both pyramidal and nonpyramidal neurons. The ultrastructural immunogold study in P21 rat hippocampi corroborated the light-microscopy results. In addition, this study revealed that a portion of the silver-intensified colloidal gold particles were located on neuronal plasmalemma, as expected for a functional cotransporter. The formation of inhibitory synapses on perikarya of the pyramidal cell layer was a late process. The density of VIAAT-immunoreactive puncta in the stratum pyramidale at P21 reached four times the P7 value in CA3, and six times the P7 value in CA1. Electron microscopy revealed that the number of synapses per neuronal perikaryal profile in the stratum pyramidale of the CA3 area at P21 was three times higher than at P7, even if a concomitant 20% increase in the area of these neuronal perikaryal profiles occurred. It is concluded that, in hippocampal pyramidal cells, there is a developmental shift in the NKCC localization from a predominantly somatic to a predominantly dendritic location. The presence of NKCC during the first postnatal week is consistent with the hypothesis that this transporter might be involved in the depolarizing effects of GABA. The depolarizing effects of GABA may not be required for the establishment of the majority of GABAergic synapses in the stratum pyramidale, because their number increases after the first postnatal week, when GABA action becomes hyperpolarizing. [source] Gephyrin, a major postsynaptic protein of GABAergic synapsesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2000Marco Sassoè-Pognetto Abstract ,-aminobutyric acid type A (GABAA) receptors are located at the majority of inhibitory synapses in the mammalian brain. However, the mechanisms by which GABAA receptor subunits are targeted to, and clustered in, the postsynaptic membrane are poorly understood. Recent studies have demonstrated that gephyrin, a protein first identified as a component of the glycine receptor (GlyR) complex, is colocalized with several subtypes of GABAA receptors and is involved in the stabilization of postsynaptic GABAA receptor clusters. Thus, gephyrin functions as a clustering protein for major subtypes of inhibitory ion channel receptors. [source] Glutamate spillover augments GABA synthesis and release from axodendritic synapses in rat hippocampusHIPPOCAMPUS, Issue 1 2010Misty M. Stafford Abstract Tight coupling between gamma-aminobutyric acid (GABA) synthesis and vesicle filling suggests that the presynaptic supply of precursor glutamate could dynamically regulate inhibitory synapses. Although the neuronal glutamate transporter excitatory amino acid transporter 3 (EAAT3) has been proposed to mediate such a metabolic role, highly efficient astrocytic uptake of synaptically released glutamate normally maintains low-extracellular glutamate levels. We examined whether axodendritic inhibitory synapses in stratum radiatum of hippocampal area CA1, which are closely positioned among excitatory glutamatergic synapses, are regulated by synaptic glutamate release via presynaptic uptake. Under conditions of spatially and temporally coordinated release of glutamate and GABA within pyramidal cell dendrites, blocking glial glutamate uptake enhanced quantal release of GABA in a transporter-dependent manner. These physiological findings correlated with immunohistochemical studies revealing expression of EAAT3 by interneurons and uptake of D-asparate into putative axodendritic inhibitory terminals only when glial uptake was blocked. These results indicate that spillover of glutamate between adjacent excitatory and inhibitory synapses can occur under conditions when glial uptake incompletely clears synaptically released glutamate. Our anatomical studies also suggest that perisomatic inhibitory synapses, unlike synapses within dendritic layers of hippocampus, are not capable of glutamate uptake and therefore transporter-mediated dynamic regulation of inhibition is a unique feature of axodendritic synapses that may play a role in maintaining a homeostatic balance of inhibition and excitation. © 2009 Wiley-Liss, Inc. [source] Expression of GABAB Receptors in Magnocellular Neurosecretory Cells of Male, Virgin Female and Lactating RatsJOURNAL OF NEUROENDOCRINOLOGY, Issue 7 2005D. S. Richards Abstract GABA is one of the key neurotransmitters that regulate the firing activity of neurones in the supraoptic (SON) and paraventricular (PVN) nuclei. In the present study, we used immunohistochemical techniques to study the distribution and subcellular localisation of metabotropic GABAB receptors in magnocellular neurones in the SON and PVN. Robust GABAB receptor immunoreactivity (GABABR; both subunit 1 and subunit 2 of the heterodimer), was observed in the SON and PVN. At the light microcope level, GABABR immonoreactivity displayed a clustered pattern localised both intracytoplasmically and at the plasma membrane. Densitometry analysis indicated that GABABR immunoreactivity was significantly more intense in vasopressin cells than in oxytocin cells, both in male, virgin female and lactating rats, and was denser in males than in virgin females. Light and electron microscope studies indicated that cytoplasmic GABABR was localised in various organelles, including the Golgi, early endosomes and lysosomes, suggesting the cycling of the receptor within the endocytic and trafficking pathways. Some smaller clusters at the level of the cell plasma membrane were apposed to glutamic acid decarboxylase 67 immunoreactive boutons, and appeared to be colocalised with gephyrin, a constituent protein of the postsynaptic density at inhibitory synapses. The presence of GABABR immunoreactivity at synaptic and extrasynaptic sites was supported by electron microscopy. These results provide anatomical evidence for the expression of postsynaptic GABAB receptors in magnocellular neurosecretory cells. [source] Demonstration of Postsynaptic Receptor Plasticity in an Amphibian Neuroendocrine InterfaceJOURNAL OF NEUROENDOCRINOLOGY, Issue 11 2002B. G. Jenks Abstract Pituitary pars intermedia melanotrope cells are often used as a model to study mechanisms of neuroendocrine integration. In the amphibian Xenopus laevis, the synthesis and release of ,-melanophore-stimulating hormone (,-MSH) from these cells is a dynamic process dependent upon the colour of background. In animals on a black background, there is a higher level of synthesis and secretion of ,-MSH than in animals on a white background, and, consequently, there is skin darkening in animals on a black background. The melanotropes are innervated by hypothalamic neurones that produce neuropeptide Y (NPY), a peptide that inhibits ,-MSH secretion via the NPY Y1 receptor. The inhibitory neurones have a higher expression of NPY in animals adapted to a white background and both the size and the number of inhibitory synapses on the melanotrope cells are enhanced. The purpose of the present study was to determine if this presynaptic plasticity displayed by the inhibitory neurones is reciprocated by postsynaptic plasticity (i.e. if there is an enhanced expression of the Y1 receptor in melanotropes of animals adapted to a white background). For this purpose quantitative real-time reverse transcriptase-polymerase chain reaction was used to determine the level of Y1 receptor mRNA in melanotropes of animals undergoing the process of background adaptation. The results showed that there is a higher Y1 receptor mRNA expression in melanotropes of white-adapted animals. We conclude that the inhibitory neuroendocrine interface in the Xenopus pars intermedia displays postsynaptic plasticity in response to changes of background colour. To our knowledge, this is the first demonstration of a physiological environmental change leading to changes in postsynaptic receptor expression in a fully identified vertebrate neuroendocrine reflex. [source] Synaptic localization of neuroligin 2 in the rodent retina: Comparative study with the dystroglycan-containing complexJOURNAL OF NEUROSCIENCE RESEARCH, Issue 4 2010Leona Lui Abstract Several recent studies have shown that neuroligin 2 (NL2), a component of the cell adhesion neurexins,neuroligins complex, is localized postsynaptically at hippocampal and other inhibitory synapses throughout the brain. Other studies have shown that components of the dystroglycan complex are also localized at a subset of inhibitory synapses and are coexpressed with NL2 in brain. These data prompted us to undertake a comparative study between the localization of NL2 and the dystroglycan complex in the rodent retina. First, we determined that NL2 mRNA is expressed both in the inner and in the outer nuclear layers. Second, we found that NL2 is localized both in the inner and in the outer synaptic plexiform layers. In the latter, the horseshoe-shaped pattern of NL2 and its extensive colocalization with RIM2, a component of the presynaptic active zone at ribbon synapses, argue that NL2 is localized presynaptically at photoreceptor terminals. Third, comparison of NL2 and the dystroglycan complex distribution patterns reveals that, despite their coexpression in the outer plexiform layer, they are spatially segregated within distinct domains of the photoreceptor terminals, where NL2 is selectively associated with the active zone and the dystroglycan complex is distally distributed in the lateral regions. Finally, we report that the dystroglycan deficiency in the mdx3cv mouse does not alter NL2 localization in the outer plexiform layer. These data show that the NL2- and dystroglycan-containing complexes are differentially localized in the presynaptic photoreceptor terminals and suggest that they may serve distinct functions in retina. © 2009 Wiley-Liss, Inc. [source] Symmetric synaptic patterns between starburst amacrine cells and direction selective ganglion cells in the rabbit retinaTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 1 2008Yung-Cheng Chen Abstract Inputs from starburst amacrine cells (SACs) to ON-OFF direction selective ganglion cells (DSGCs) in the rabbit retina are themselves directional. However, the synaptic asymmetry between SACs and DSGCs required for generating direction selectivity has been controversial. We investigated dendritic contacts and distribution of inhibitory synapses between SACs and their overlapped DSGCs. Double injection of SAC/DSGC pairs and quantitative analysis revealed no obvious asymmetry of dendritic contacts between SACs and DSGCs. Furthermore, examination of the inhibitory input pattern on the dendrites of DSGCs using antibodies against GABAA receptors also suggested an isotropic arrangement with the overlapping SACs in both the preferred and the null directions. Therefore, the presynaptic mechanism of direction selectivity upon DSGCs may not result from a simple asymmetric arrangement with overlapping SACs. Multiple layer interactions and sophisticated synaptic connections between SACs and DSGCs are necessary. J. Comp. Neurol. 508:175,183, 2008. © 2008 Wiley-Liss, Inc. [source] Synaptic organization of complex ganglion cells in rabbit retina: Type and arrangement of inputs to directionally selective and local-edge-detector cellsTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 4 2005Edward V. Famiglietti Abstract The type and topographic distribution of synaptic inputs to a directionally selective (DS) rabbit retinal ganglion cell (GC) were examined and were compared with those received by two other complex GC types. The percentage of cone bipolar cell (BC) input, presumably an index of sustained responses and simple receptive field properties, is much higher than expected for complex GCs in reference to previous reports in other species: approximately 20% for the type 1 bistratified ON,OFF DS GC and for a multistratified GC, and approximately 40% for the small-tufted local-edge-detector GC. Consistent with a previous study (Famiglietti [1991] J. Comp. Neurol. 309:40,70), no ultrastructural evidence is found for inhibitory synapses from starburst amacrine cells to the ON,OFF DS GC. The density of inputs to the ON,OFF DS GC is high and rather evenly distributed over the dendritic tree. Clustering of inputs brings excitatory and inhibitory inputs into proximity, but the strict on-path condition of more proximal inhibitory inputs, favoring shunting inhibition, is not satisfied. Prominent BC input and its regional variation suggest that BCs play key roles in DS neural circuitry, both pre- and postsynaptic to the ON,OFF DS GC, according to a bilayer model (Famiglietti [1993] Invest. Ophthalmol. Vis. Sci. 34:S985). Asymmetry of inhibitory amacrine cell input may signify a region on the preferred side of the receptive field, the inhibition-free zone (Barlow and Levick [1965] J. Physiol. (Lond.) 178:477,504), supporting a role for postsynaptic integration in the DS mechanism. Prominent BC input to the local-edge-detector, often without accompanying amacrine cell input, indicates presynaptic integration in forming its trigger feature. J. Comp. Neurol. 484:357,391, 2005. © 2005 Wiley-Liss, Inc. [source] GABAB receptor modulation of excitatory and inhibitory synaptic transmission onto rat CA3 hippocampal interneuronsTHE JOURNAL OF PHYSIOLOGY, Issue 2 2003Saobo Lei Hippocampal stratum radiatum inhibitory interneurons receive glutamatergic excitatory innervation via the recurrent collateral fibers of CA3 pyramidal neurons and GABAergic inhibition from other interneurons. We examined both presynaptic- and postsynaptic-GABAB receptor-mediated responses at both synapse types. Postsynaptic GABAB receptor-mediated responses were absent in recordings from young (P16-18) but present in recordings from older animals (P30) suggesting developmental regulation. In young animals, the GABAB receptor agonist, baclofen, inhibited the amplitude of evoked EPSCs and IPSCs, an effect blocked by prior application of the selective antagonist CGP55845. Baclofen enhanced the paired-pulse ratio and coefficient of variation of evoked EPSCs and IPSCs, consistent with a presynaptic mechanism of regulation. In addition, baclofen reduced the frequency of miniature IPSCs but not mEPSCs. However, baclofen reduced the frequency of KCl-induced mEPSCs; an effect blocked by Cd2+, implicating presynaptic voltage-gated Ca2+ channels as a target for baclofen modulation. In contrast, although Cd2+ prevented the KCl-induced increase in mIPSC frequency, it failed to block baclofen's reduction of mIPSC frequency. Whereas N- and P/Q-types of Ca2+ channels contributed equally to GABAB receptor-mediated inhibition of EPSCs, more P/Q-type Ca2+ channels were involved in GABAB receptor-mediated inhibition of IPSCs. Finally, baclofen blocked the frequency-dependent depression of EPSCs and IPSCs, but was less effective at blocking frequency-dependent facilitation of EPSCs. Our results demonstrate that presynaptic GABAB receptors are expressed on the terminals of both excitatory and inhibitory synapses onto CA3 interneurons and that their activation modulates essential components of the release process underlying transmission at these two synapse types. [source] Developmental change in GABAA receptor desensitization kinetics and its role in synapse function in rat cortical neuronsTHE JOURNAL OF PHYSIOLOGY, Issue 1 2000Bruce Hutcheon We examined the maturation of GABAA receptor synapses in cortical pyramidal neurons cultured from embryonic rats. The decay kinetics of GABAA receptor-mediated miniature postsynaptic currents (mPSCs) were compared with those of responses evoked by GABA in excised membrane patches. Fast perfusion of 1 or 10 mM GABA on membrane patches evoked currents with different desensitizing time courses in young and old neurons. For neurons older than 4 days in vitro (DIV), GABAA currents had a fast component of desensitization (median , 3 ms) seldom seen in patches from younger neurons. In contrast, mPSCs exhibited a substantial fast component of decay at 2,4 DIV that became more prominent with further development although the median value of its time constant remained unchanged. The selective ,3 subunit positive modulator SB-205384 had no effect on mPSCs at any time in vitro but potentiated extrasynaptic activity. This suggests that synapse maturation does not proceed by a gradual exchange of early embryonic GABAA receptor subforms for adult forms. At all ages, the kinetic properties of mPSCs were heterogeneous. This heterogeneity extended to the level of mPSCs from single neurons and may be a normal aspect of synaptic functioning. These results suggest that inhibitory synapses in developing neurons are capable of selectively capturing GABAA receptors having fast desensitization kinetics. This functional preference probably reflects the developmental turning point from an inwardly looking trophic capacity of embryonic GABAA receptors to a role concerned with information processing. [source] | ||||||||||