GABAergic

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

Immunohistochemical localization of GABAB receptors in the rat central nervous system

Abstract: The recent cloning of two gamma-aminobutyric acid(B) (GABA(B)) receptor isoforms (GABA(B)R1a/b), which are probably splice variants of the same gene transcript, allowed us to develop an antiserum that recognized the receptors in fixed tissue and to map their distribution in the rat central nervous system (CNS). We also investigated whether GABA(B)R1 colocalizes with glutamic acid decarboxylase (GAD), a marker of GABAergic cell bodies and terminals. Although GABA(B)R1-like immunoreactivity (GABA(B)R1-LI) was distributed throughout the CNS, several distinct distribution patterns emerged: (1) all monoaminergic brainstem cell groups appeared to contain very high levels of GABA(B)R1, (2) a very high intensity of GABA(B)R1-LI was observed in the majority of the cholinergic regions in the CNS, with exception of motoneurons of the third through sixth cranial nerve nuclei, and (3) a low density of the receptor was observed in most of the nuclei that contain cell bodies of GABAergic projection neurons. The highest GABA(B)R1 labeling was observed in the thalamus, interpeduncular nucleus and medial habenula. Cell bodies were labeled throughout the neuroaxis. We also observed dense neuropil labeling in many regions, suggesting that this receptor is localized in dendrites and/or axon terminals. However, in immunofluorescent double-labeling experiments for GABA(B)R1 and GAD, we never observed GABA(B)R1-LI in GAD-positive axon terminals; this result suggests that the GABA(B)R1 may not function as an autoreceptor. Double labeling was observed in the cell bodies of Purkinje neurons and in some interneurons. In general, the immunohistochemical localization of the GABA(B)R1 correlates well with physiologic and autoradiographic data on the distribution of GABA(B) receptors, but some critical differences were noted. Thus, it is likely that additional GABA(B) receptor subtypes remain to be identified.

The contribution of GABA to glutamate/glutamine cycling and energy metabolism in the rat cortex in vivo

Abstract: Previous studies have shown that the glutamate/glutamine (Glu/Gln) neurotransmitter cycle and neuronal glucose oxidation are proportional (1:1), with increasing neuronal activity above isoelectricity. GABA, a product of Glu metabolism, is synthesized from astroglial Gln and contributes to total Glu/Gln neurotransmitter cycling, although the fraction contributed by GABA is unknown. In the present study, we used 13C NMR spectroscopy together with i.v. infusions of [1,6-13C2]glucose and [2-13C]acetate to separately determine rates of Glu/Gln and GABA/Gln cycling and their respective tricarboxylic acid cycles in the rat cortex under conditions of halothane anesthesia and pentobarbital-induced isoelectricity. Under 1% halothane anesthesia, GABA/Gln cycle flux comprised 23% of total (Glu plus GABA) neurotransmitter cycling and 18% of total neuronal tricarboxylic acid cycle flux. In isoelectric cortex, glucose oxidation was reduced >3-fold in glutamatergic and GABAergic neurons, and neurotransmitter cycling was below detection. Hence, in both cell types, the primary energetic costs are associated with neurotransmission, which increase together as cortical activity is increased. The contribution of GABAergic neurons and inhibition to cortical energy metabolism has broad implications for the interpretation of functional imaging signals.

BDNF regulates spontaneous correlated activity at early developmental stages by increasing synaptogenesis and expression of the K+/Cl- co-transporter KCC2.

Abstract: Spontaneous neural activity is a basic property of the developing brain, which regulates key developmental processes, including migration, neural differentiation and formation and refinement of connections The mechanisms regulating spontaneous activity are not known By using transgenic embryos that overexpress BDNF under the control of the nestin promoter, we show here that BDNF controls the emergence and robustness of spontaneous activity in embryonic hippocampal slices Further, BDNF dramatically increases spontaneous co-active network activity, which is believed to synchronize gene expression and synaptogenesis in vast numbers of neurons In fact, BDNF raises the spontaneous activity of E18 hippocampal neurons to levels that are typical of postnatal slices We also show that BDNF overexpression increases the number of synapses at much earlier stages (E18) than those reported previously Most of these synapses were GABAergic, and GABAergic interneurons showed hypertrophy and a 3-fold increase in GAD expression Interestingly, whereas BDNF does not alter the expression of GABA and glutamate ionotropic receptors, it does raise the expression of the recently cloned K(+)/Cl(-) KCC2 co-transporter, which is responsible for the conversion of GABA responses from depolarizing to inhibitory, through the control of the Cl(-) potential Together, results indicate that both the presynaptic and postsynaptic machineries of GABAergic circuits may be essential targets of BDNF actions to control spontaneous activity The data indicate that BDNF is a potent regulator of spontaneous activity and co-active networks, which is a new level of regulation of neurotrophins Given that BDNF itself is regulated by neuronal activity, we suggest that BDNF acts as a homeostatic factor controlling the emergence, complexity and networking properties of spontaneous networks