GABAergic

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

Development of the GABAergic System from Birth to Adolescence

Abstract: The neurotransmitter GABA (γ-aminobutyric acid), acting via inotropic GABA(A) and metabotropic GABA(B) receptors, plays an essential role in a variety of distinct neuronal processes, including regulation of neuronal excitability, determination of temporal aspects of spike trains, control of the size and propagation of neuronal assemblies, generation of oscillatory activity, and neuronal plasticity. Although the developmental switch between excitatory and inhibitory GABA(A) receptor-mediated responses is widely appreciated, the fact that the postnatal maturation of the GABAergic system lasts until late adolescence is not so persuasively promoted. This review summarizes recent knowledge of the maturation of various aspects of the GABAergic systems, like functional expression of GABA synthesizing/degrading enzymes and transporters, density of GABAergic synapses, GABAergic projection patterns, GABA receptor subunit composition, and properties of GABAergic interneurons, with an emphasis on the late developmental alterations. In addition, some aspects of the development of mental capabilities during adolescence and their relation the delayed maturation of the GABAergic system are presented.

Tonic Endovanilloid Facilitation of Glutamate Release in Brainstem Descending Antinociceptive Pathways

Abstract: Activation of transient receptor potential vanilloid-1 (TRPV1) channels in the periaqueductal gray (PAG) activates OFF antinociceptive neurons of the rostral ventromedial medulla (RVM). We examined in rats the effect of intra-ventrolateral (VL)-PAG injections of TRPV1 agonists and antagonists on the nocifensive response to heat in the plantar test, neurotransmitter (glutamate and GABA) release in the RVM, and spontaneous and tail flick-related activities of RVM neurons. The localization of TRPV1 in VL-PAG and RVM neurons was examined using various markers of glutamatergic and GABAergic neurons. Intra-VL-PAG injection of capsaicin increased the threshold of thermal pain sensitivity, whereas the selective TRPV1 antagonist 5'-iodo-resiniferatoxin (I-RTX) facilitated nociceptive responses, and blocked capsaicin analgesic effect at a dose inactive per se. Intra-VL PAG capsaicin evoked a robust release of glutamate in RVM microdialysates. I-RTX, at a dose inactive per se, blocked the effect of capsaicin, and inhibited glutamate release at a higher dose. Antinociception and hyperalgesia induced by capsaicin and I-RTX, respectively, correlated with enhanced or reduced activity of RVM OFF cells. Immunohistochemical analyses suggested that several TRPV1-immunoreactive (ir) neurons in both the VL-PAG and RVM are glutamatergic and surrounded by glutamatergic and GABAergic terminals. Our data suggest that VL-PAG neurons respond to TRPV1 stimulation by releasing glutamate into the RVM, thereby activating OFF cells and producing analgesia. The results obtained with the TRPV1 antagonist alone suggest that this pathway is tonically activated by endovanilloids.

Coordinated developmental recruitment of latent fast spiking interneurons in layer IV barrel cortex

Abstract: Feedforward inhibitory GABAergic transmission is critical for mature cortical circuit function; in the neonate, however, GABA is depolarizing and believed to have a different role. Here we show that the GABAA receptor-mediated conductance is depolarizing in excitatory (stellate) cells in neonatal (postnatal day [P]3-5) layer IV barrel cortex, but GABAergic transmission at this age is not engaged by thalamocortical input in the feedforward circuit and has no detectable circuit function. However, recruitment occurs at P6-7 as a result of coordinated increases in thalamic drive to fast-spiking interneurons, fast-spiking interneuron-stellate cell connectivity and hyperpolarization of the GABAA receptor-mediated response. Thus, GABAergic circuits are not engaged by thalamocortical input in the neonate, but are poised for a remarkably coordinated development of feedforward inhibition at the end of the first postnatal week, which has profound effects on circuit function at this critical time in development.

Response of nicotine self-administration in the rat to manipulations of mu-opioid and γ-aminobutyric acid receptors in the ventral tegmental area

Abstract: Rationale: The mesolimbic dopamine system has been implicated in the reinforcing effects of nicotine, a drug which appears to act at least in part through the ventral tegmental area (VTA). Other neuronal elements in the VTA are important in drug reward. In particular, mu opioid receptors in the VTA have been shown to influence cocaine reinforcement. Objective: The aim of this study was to test whether the mu opioid receptors in the VTA also regulate the intake of nicotine. Methods: This research was carried out with animals trained to self-administer nicotine or cocaine, or to respond for food. Mu receptors were targeted with the selective agonist [D-Ala2,N-Me-Phe4,Gly-ol5]-enkephalin (DAMGO) and γ-aminobutyric acid (GABA) receptors with the selective agonists baclofen and muscimol; each of these compounds was delivered by microinfusion into the VTA. Results: The mu-selective agonist DAMGO, tested over a dose range of 0.005–0.05 µg, had an effect at the highest dose only, where it produced a reduction in self-administration maintained by doses of either 10 µg/kg or 30 µg/kg per infusion of nicotine. Intra-VTA microinfusions of DAMGO did not reinstate extinguished responding previously established for nicotine, nor did they have prominent effects on operant behavior maintained by food. In contrast to the overall limited effects of DAMGO on nicotine self-administration, the GABA agonists muscimol and baclofen each reduced nicotine self-administration substantially when delivered into the VTA, whereas they were less effective against cocaine self-administration. Conclusions: The lesser effect of DAMGO microinfusions in the VTA on nicotine than cocaine self-administration is associated with the opposite efficacy of GABA agonists. These findings suggest that nicotine and cocaine differentially activate circuitry in which mu receptors are situated, especially GABAergic elements.

GABA receptors of insects

Abstract: Publisher Summary This chapter focuses on receptors for the neurotransmitter molecule GABA (γ-aminobutyric acid) with particular emphasis on insect GABA receptors. It discusses GABA receptors of the insect nervous system and insect muscle. GABAergic neurons are found in the brain, spinal cord, and ganglia of the mammalian nervous system. Ionophoretic application of GABA on to mammalian neurons normally results in an increased membrane conductance and an inhibitory (hyperpolarizing) response of the cell under test. GABA-sensitive cells have been detected in sympathetic ganglia cerebral cortex and Deiter's nucleus. Most responses are attributable to a GABA-operated chloride channel; they are blocked by bicuculline, the active form of which is the 1S,9R-(-)isomer and picrotoxin. The chapter also discusses GABA receptors of invertebrates other than insects, insect GABA receptors as targets for insecticides, and GABA receptors as members of a ligand-operated receptor super-family.