GABAergic

About: GABAergic is a research topic. Over the lifetime, 9595 publications have been published within this topic receiving 473568 citations.

Synchronized overproduction of neurotransmitter receptors in diverse regions of the primate cerebral cortex.

Abstract: A remarkable diversity of neurotransmitter receptors develops concurrently in disparate areas of the primate cerebral cortex. The density of dopaminergic, adrenergic, serotonergic, cholinergic, and GABAergic receptors (where GABA is gamma-aminobutyric acid) in rhesus monkey reaches a maximum level between 2 and 4 months of age and then declines gradually to adult levels in all layers of sensory, motor, and association regions. The synchronized development of neurotransmitter receptors in diverse layers and regions of the neocortex occurs pari passu with synaptogenesis, demonstrating unusual coordination of biochemical and structural maturation and supporting the hypothesis that the entire cerebral cortex matures as an integrated network, rather than as a system-by-system cascade.

Distribution of parvalbumin, calretinin, and calbindin-D(28k) immunoreactivity in the rat amygdaloid complex and colocalization with gamma-aminobutyric acid.

Abstract: To understand the organization of inhibitory circuitries in the rat amygdala, the distribution of parvalbumin, calretinin, and calbindin immunoreactivity was investigated in the rat amygdaloid complex. Colocalization of various calcium-binding proteins with the inhibitory transmitter gamma-aminobutyric acid (GABA) was studied by using the mirror technique. Parvalbumin-immunoreactive (-ir) elements were located mostly in the deep amygdaloid nuclei, whereas the calretinin-ir and calbindin-ir staining were most intense in the cortical nuclei as well as in the central nucleus and the amygdalohippocampal area. Second, the distribution of immunopositive neurons largely parallelled the distribution of terminal and neuropil labeling. Third, immunostained neurons could be divided into four major morphologic types (types 1-4) based on the characteristics of the somata and the dendritic trees. The fourth lightly stained neuronal type that had a pyramidal GABA-negative soma was observed only in calretinin and calbindin preparations. Fourth, parvalbumin-ir terminals formed basket-like plexus and cartridges, which suggests that parvalbumin labels GABAergic inhibitory basket cells and axo-axonic chandelier cells, respectively. Colocalization studies indicated that 521 of 553 (94%) of parvalbumin-ir, 419 of 557 (75%) of calbindin-ir, and 158 of 657 (24%) of calretinin-ir neurons were GABA-positive in the deep amygdaloid nuclei. A high density of large GABA-negative calbindin-ir neurons was observed caudally in the medial division of the lateral nucleus and GABA-negative calretinin-ir neurons were observed in the magnocellular division of the accessory basal nucleus as well as in the intermediate and parvicellular divisions of the basal nucleus. These data suggest that in various amygdaloid areas, neuronal excitability is controlled by GABAergic neurons that contain different calcium-binding proteins. The appearance of basket-like plexus and cartridges in the parvalbumin preparations, but not in calretinin preparations, suggests that like in the hippocampus, the distribution of inhibitory terminals in the dendritic and perisomatic regions of postsynaptic neurons in the rat amygdala is organized in a topographic manner.

Disruption of GABAA Receptors on GABAergic Interneurons Leads to Increased Oscillatory Power in the Olfactory Bulb Network

Abstract: Synchronized neural activity is believed to be essential for many CNS functions, including neuronal development, sensory perception, and memory formation. In several brain areas GABA(A) receptor-mediated synaptic inhibition is thought to be important for the generation of synchronous network activity. We have used GABA(A) receptor beta3 subunit deficient mice (beta3-/-) to study the role of GABAergic inhibition in the generation of network oscillations in the olfactory bulb (OB) and to reveal the role of such oscillations in olfaction. The expression of functional GABA(A) receptors was drastically reduced (>93%) in beta3-/- granule cells, the local inhibitory interneurons of the OB. This was revealed by a large reduction of muscimol-evoked whole-cell current and the total current mediated by spontaneous, miniature inhibitory postsynaptic currents (mIPSCs). In beta3-/- mitral/tufted cells (principal cells), there was a two-fold increase in mIPSC amplitudes without any significant change in their kinetics or frequency. In parallel with the altered inhibition, there was a significant increase in the amplitude of theta (80% increase) and gamma (178% increase) frequency oscillations in beta3-/- OBs recorded in vivo from freely moving mice. In odor discrimination tests, we found beta3-/- mice to be initially the same as, but better with experience than beta3+/+ mice in distinguishing closely related monomolecular alcohols. However, beta3-/- mice were initially better and then worse with practice than control mice in distinguishing closely related mixtures of alcohols. Our results indicate that the disruption of GABA(A) receptor-mediated synaptic inhibition of GABAergic interneurons and the augmentation of IPSCs in principal cells result in increased network oscillations in the OB with complex effects on olfactory discrimination, which can be explained by an increase in the size or effective power of oscillating neural cell assemblies among the mitral cells of beta3-/- mice.

Inhibitory synapses in the developing auditory system are glutamatergic.

Abstract: Activity-dependent synapse refinement is crucial for the formation of precise excitatory and inhibitory neuronal circuits. Whereas the mechanisms that guide refinement of excitatory circuits are becoming increasingly clear, the mechanisms guiding inhibitory circuits have remained obscure. In the lateral superior olive (LSO), a nucleus in the mammalian sound localization system that receives inhibitory input from the medial nucleus of the trapezoid body (MNTB), specific elimination and strengthening of synapses that are both GABAergic and glycinergic (GABA/glycinergic synapses) is essential for the formation of a precise tonotopic map. We provide evidence that immature GABA/glycinergic synapses in the rat LSO also release the excitatory neurotransmitter glutamate, which activates postsynaptic NMDA receptors (NMDARs). Immunohistochemical studies demonstrate synaptic colocalization of the vesicular glutamate transporter 3 with the vesicular GABA transporter, indicating that GABA, glycine and glutamate are released from single MNTB terminals. Glutamatergic transmission at MNTB-LSO synapses is most prominent during the period of synapse elimination. Synapse-specific activation of NMDARs by glutamate release at GABAergic and glycinergic synapses could be important in activity-dependent refinement of inhibitory circuits.

Localization of glutamic-acid-decarboxylase-immunoreactive axon terminals in the inferior olive of the rat, with special emphasis on anatomical relations between GABAergic synapses and dendrodendritic gap junctions

Abstract: Immunocytochemical and electron microscopic methods were used to examine the GABAergic innervation of the inferior olivary nucleus in adult rats. This neuronal system was visualized with an antibody against glutamic acid decarboxylase (GAD, EC 4.1.1.15), the GABA-synthesizing enzyme. A GAD-positive reaction product was encountered only in short segments of preterminal axons and in axon terminals. Their relative number per unit area of neuropil was very similar in all olivary subnuclei. Despite this homogeneity in density, obvious intraregional differences existed. Some regions were strongly immunoreactive (the “c” subgroup, the s nucleus, and the mediolateral outgrowth of the medial accessory olive), whereas others were weakly labeled (the dorsomedial cell column and the central zones of the medial accessory and principal olives). The strongly immunoreactive areas contained the largest and most intensively labeled axon terminals. Areas of weak labeling were filled with small, weakly immunoreactive nerve terminals. Thus, variations in size and in intensity of labeling create a specific pattern of GABA innervation, revealed by an almost continuous gradient between the above-mentioned extremes. The GAD-positive axon terminals established conventional synapses with dendrites (94% of the samples) or with cell bodies (6%). The vast majority of these synapses were type II (84%) and only a small proportion formed type I synaptic contacts (16%), regardless of the nature of the postsynaptic element. Immunoreactive terminals were also involved in the complex synaptic arrangements---the glomeruli, which characterize the olivary neuropil. Within these formations, olivary neurons were electrotonically coupled through dendrodendritic gap junctions. There was a constant association between GAD-positive axon terminals and small dendritic appendages linked by gap junctions. This association was revealed not only by the systematic presence of immunolabeled terminals directly apposed to the dendritic appendages but, more importantly, by the frequent presence of type II synapses straddling both elements. These synapses were in close proximity to the low-resistance pathways represented by the gap junctions. The strategic location of these GABA synapses is discussed in relation to recent findings indicating the possibility of a synaptic modulation of the electrical coupling: the release of GABA, by increasing nonjunctional membrane conductance, could shunt the coupling between olivary neurons. The functional decoupling of selected gap junctions would be responsible for the spatial organization of the olivary electrotonic coupling.