GABAergic

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

Neuronal Glutamate Uptake Contributes to GABA Synthesis and Inhibitory Synaptic Strength

Abstract: Neurons must maintain a supply of neurotransmitter in their presynaptic terminals to fill synaptic vesicles. GABA is taken up into inhibitory terminals by transporters or is synthesized from glutamate by glutamic acid decarboxylase. Here we report that glutamate transporters supply GABAergic terminals in the hippocampus with glutamate, which is then used to synthesize GABA for filling synaptic vesicles. Glutamate transporter antagonists reduced IPSC and miniature IPSC (mIPSC) amplitudes, consistent with a reduction in the amount of GABA packaged into each synaptic vesicle. This reduction occurred rapidly and independently of synaptic activity, suggesting that modulation of vesicular GABA content does not require vesicle release and refilling. Raising extracellular glutamate levels increased mIPSC amplitudes by enhancing glutamate uptake and, consequently, GABA synthesis. These results indicate that neuronal glutamate transporters strengthen inhibitory synapses in response to extracellular glutamate. This modulation appears to occur under normal conditions and may constitute a negative feedback mechanism to combat hyperexcitability.

Immunocytochemistry of GABA in the antennal lobes of the sphinx moth Manduca sexta.

Abstract: We have prepared and characterized specific rabbit antisera against γ-aminobutyric acid (GABA) coupled covalently to bovine serum albumin and keyhole-limpet hemocyanin. Using these antisera in immunocytochemical staining procedures, we have probed the antennal lobes and their afferent and efferent fiber tracts in the sphinx moth Manduca sexta for GABA-like immunoreactivity in order to map putatively GABAergic central neurons in the central antennal-sensory pathway. About 30% of the neuronal somata in the large lateral group of cell bodies in the antennal lobe are GABA-immunoreactive; cells in the medial and anterior groups of antennal-lobe cells did not exhibit GABA-like immunoreactivity. GABA-immunoreactive neurites had arborizations in all of the glomeruli in the antennal lobe. Double-labeling experiments involving tandem intracellular staining with Lucifer Yellow and immunocytochemical staining for GABA-like immunoreactivity demonstrated that at least some of the GABA-immunoreactive cells in the antennal lobe are amacrine local interneurons. Several fiber tracts that carry axons of antennal-lobe projection neurons exhibited GABA-immunoreactive fibers. Among the possibly GABA-containing projection neurons are several cells, with somata in the lateral group of the antennal lobe, that send their axons directly to the lateral protocerebmm.

Selective GABAergic innervation of thalamic nuclei from zona incerta

Abstract: Thalamocortical circuits that govern cortical rhythms and ultimately effect sensory transmission consist of three major interconnected elements: excitatory thalamocortical and corticothalamic neurons and GABAergic cells in the reticular thalamic nucleus. Based on the present results, a fourth component has to be added to this scheme. GABAergic fibres from an extrareticular diencephalic source were found to selectively innervate relay cells located mainly in higher-order thalamic nuclei. The origin of this pathway was localized to zona incerta (ZI), known to receive collaterals from corticothalamic fibres. First-order nuclei were innervated only in zones showing a high density of calbindin-positive neurons. The large GABA-immunoreactive incertal terminals established multiple contacts preferentially on the proximal dendrites of relay cells via symmetrical synapses with multiple release sites. The distribution, ultrastructural characteristics and postsynaptic target selection of extrareticular terminals were similar to type II muscarinic acetylcholine receptor-positive boutons, which constituted up to 49% of all GABAergic terminals in the posterior nucleus. This suggests that a significant proportion of the GABAergic input into certain thalamic territories involved in higher-order functions may have extrareticular origin. Unlike the reticular nucleus, ZI receives peripheral and layer V cortical input but no thalamic feedback; it projects to brainstem centres and has extensive intranuclear recurrent collaterals. This indicates that ZI exerts a conceptually new type of inhibitory control over the thalamus. The proximally situated, multiple active zones of ZI terminals indicate a powerful influence on the firing properties of thalamic neurons, which is conveyed to multiple cortical areas via relay cells which have widespread projections to neocortex.

Postsynaptic targets of Purkinje cell terminals in the cerebellar and vestibular nuclei of the rat

Abstract: The cerebellar and vestibular nuclei consist of a heterogeneous group of inhibitory and excitatory neurons. A major proportion of the inhibitory neurons provides a GABAergic feedback to the inferior olive, while the excitatory neurons exert more direct effects on motor control via non-olivary structures. At present is is not clear whether Purkinje cells innervate all types of neurons in the cerebellar and vestibular nuclei or whether an individual Purkinje cell axon can innervate different types of neurons. In the present study, we studied the postsynaptic targets of Purkinje cell axons in the rat using a combination of pre-embedding immunolabelling of the Purkinje cell terminals by L7, a Purkinje cell-specific marker, and postembedding GABA and glycine immunocytochemistry. In the cerebellar nuclei, vestibular nuclei and nucleus prepositus hypoglossi Purkinje cell terminals were found apposed to GABAergic and glycinergic neurons as well as to larger non-GABAergic, non-glycinergic neurons. In the cerebellar and vestibular nuclei individual Purkinje cell terminals innervated both the inhibitory and excitatory neurons. Both types of neurons were contacted no only by non-GABAergic Purkinje cell terminals but also by GABA-containing terminals that were not labelled for L7 and by non-GABAergic, non-glycinergic terminals that formed excitatory synapses. Glycine-containing terminals were relatively scarce ( < 2% of the GABA-containing terminals) and frequently contacted the larger non-GABAergic, non-glycinergic neurons. To summarize, Purkinje cell axons evoke their effects through different types of neurons present in the cerebellar and vestibular nuclear complex. The observation that individual Purkinje cells can innervate both excitatory and inhibitory neurons suggests that the excitatory cerebellar output system and the inhibitory feedback to the inferior olive are controlled simultaneously.