GABAergic

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

A class of GABAergic neurons in the prefrontal cortex sends long-range projections to the nucleus accumbens and elicits acute avoidance behavior

Abstract: GABAergic projections from the neocortex to subcortical structures have been poorly characterized. Using Dlxi12b–Cre mice, we found anatomical evidence for GABAergic neurons that project from the mouse medial prefrontal cortex (mPFC) to multiple subcortical targets. We used a combination of patch-clamp electrophysiology, optogenetics, and pharmacology to confirm that Dlxi12b-labeled projections from the mPFC to the nucleus accumbens (NAcc) release GABA and do not corelease glutamate. Furthermore, optogenetic stimulation of these GABAergic projections from mPFC to NAcc induces avoidance behavior in a real-time place preference task, suggesting that these long-range projecting GABAergic neurons can transmit aversive signals. Finally, we found evidence for heterogeneous histochemical and/or electrophysiological properties of long-range projecting GABAergic neurons in the mPFC. Some of these neurons were labeled in parvalbumin–Cre and vasoactive intestinal peptide–Cre mice. We also used a novel intersectional targeting strategy to label GABAergic neurons in the mPFC that project to NAcc and found that these neurons have fast-spiking properties and express parvalbumin. These results define possible functions and properties for a class of long-range projecting GABAergic neurons in the neocortex.

Fragile X syndrome: the GABAergic system and circuit dysfunction.

Abstract: Fragile X syndrome (FXS) is a neurodevelopmental disorder characterized by intellectual disability, sensory hypersensitivity, and high incidences of autism spectrum disorders and epilepsy. These phenotypes are suggestive of defects in neural circuit development and imbalances in excitatory glutamatergic and inhibitory GABAergic neurotransmission. While alterations in excitatory synapse function and plasticity are well-established in Fmr1 knockout (KO) mouse models of FXS, a number of recent electrophysiological and molecular studies now identify prominent defects in inhibitory GABAergic transmission in behaviorally relevant forebrain regions such as the amygdala, cortex, and hippocampus. In this review, we summarize evidence for GABAergic system dysfunction in FXS patients and Fmr1 KO mouse models alike. We then discuss some of the known developmental roles of GABAergic signaling, as well as the development and refinement of GABAergic synapses as a framework for understanding potential causes of mature circuit dysfunction. Finally, we highlight the GABAergic system as a relevant target for the treatment of FXS.

Defective dentate nucleus GABA receptors in essential tremor

Abstract: The development of new treatments for essential tremor, the most frequent movement disorder, is limited by a poor understanding of its pathophysiology and the relative paucity of clinicopathological studies. Here, we report a post-mortem decrease in GABAA (35% reduction) and GABAB (22–31% reduction) receptors in the dentate nucleus of the cerebellum from individuals with essential tremor, compared with controls or individuals with Parkinson's disease, as assessed by receptor-binding autoradiography. Concentrations of GABAB receptors in the dentate nucleus were inversely correlated with the duration of essential tremor symptoms ( r 2 = 0.44, P < 0.05), suggesting that the loss of GABAB receptors follows the progression of the disease. In situ hybridization experiments also revealed a diminution of GABAB(1a+b) receptor messenger RNA in essential tremor (↓27%). In contrast, no significant changes of GABAA and GABAB receptors (protein and messenger RNA), GluN2B receptors, cytochrome oxidase-1 or GABA concentrations were detected in molecular or granular layers of the cerebellar cortex. It is proposed that a decrease in GABA receptors in the dentate nucleus results in disinhibition of cerebellar pacemaker output activity, propagating along the cerebello-thalamo-cortical pathways to generate tremors. Correction of such defective cerebellar GABAergic drive could have a therapeutic effect in essential tremor. * Abbreviations : GABA : γ-aminobutyric acid

Topographical organization of GABAergic neurons within the ventral tegmental area of the rat.

Abstract: The ventral tegmental area (VTA), the origin of dopaminergic cell bodies that comprise the mesocorticolimibic DA system, is widely implicated in drug and natural reward, cognition, and several psychiatric disorders. In addition to dopaminergic neurons, this region is populated by GABAergic neurons, which both regulate the firing of their dopaminergic counterparts and send projections throughout the brain. Although the dopaminergic neurons of the VTA have been extensively characterized neuroanatomically, much less is known about the GABAergic neurons in this region. Recent data suggest that the rostro-caudal topographic organization of these GABAergic neurons may correspond to their ability to regulate drug reward. In the present study, we used immunohistochemical techniques to examine the frequency and topography of GABAergic neurons throughout the rostro-caudal axis of the VTA and the extent to which they coexpress other proteins, including tyrosine hydroxylase (a marker of DA neurons), cholecystokinin, parvalbumin, calretinin, and calbindin d 28k. Synapse 61:87–95, 2007. © 2006 Wiley-Liss, Inc.

Predominance of corticothalamic synaptic inputs to thalamic reticular nucleus neurons in the rat

Abstract: Quantitative electron microscopy was used to examine the relative contributions of different types of synapses to the circuitry of the thalamic reticular nucleus (RTN) in the rat. Single RTN cells were injected with Lucifer Yellow (LY) in fixed brain slices and examined after photoconversion; corticothalamic axons and terminals were labeled by anterograde transport of Phaseolus vulgaris–leucoagglutinin (PHA-L); and γ-aminobutyric acid (GABA)ergic terminals were labeled by postembedding immunocytochemistry. Three types of synapses, made by morphologically distinguishable small terminals (ST), large terminals (LT), and GABAergic terminals, were distributed on all portions of the dendritic trees of injected RTN cells. ST and LT terminals formed asymmetrical, presumed excitatory, synaptic contacts. On proximal dendrites, approximately 50% of the synapses were ST, 30–40% were LT, and 10–25% were GABAergic. On distal dendrites, 60–65% were ST, 20% were LT, and 15% were GABAergic. PHA-L labeling showed that labeled corticothalamic terminals and ST terminals have identical morphological features and the same distribution patterns on RTN dendrites, indicating that the majority of excitatory afferents to RTN neurons are derived from the cerebral cortex. The LT terminals found in smaller numbers are probably derived from collateral axons of thalamocortical relay cells. GABAergic terminals formed by LY-labeled, intra-RTN axon collaterals were relatively few in number, and no dendrodendritic synapses were observed. J. Comp. Neurol. 414:67–79, 1999. © 1999 Wiley-Liss, Inc.