GABAergic

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

Neurogliaform Neurons Form a Novel Inhibitory Network in the Hippocampal CA1 Area

Abstract: We studied neurogliaform neurons in the stratum lacunosum moleculare of the CA1 hippocampal area. These interneurons have short stellate dendrites and an extensive axonal arbor mainly located in the stratum lacunosum moleculare. Single-cell reverse transcription-PCR showed that these neurons were GABAergic and that the majority expressed mRNA for neuropeptide Y. Most neurogliaform neurons tested were immunoreactive for alpha-actinin-2, and many stratum lacunosum moleculare interneurons coexpressed alpha-actinin-2 and neuropeptide Y. Neurogliaform neurons received monosynaptic, DNQX-sensitive excitatory input from the perforant path, and 40 Hz stimulation of this input evoked EPSCs displaying either depression or initial facilitation, followed by depression. Paired recordings performed between neurogliaform neurons showed that 85% of pairs were electrically connected and 70% were also connected via GABAergic synapses. Injection of sine waveforms into neurons during paired recordings resulted in transmission of the waveforms through the electrical synapse. Unitary IPSCs recorded from neurogliaform pairs readily fatigued, had a slow decay, and had a strong depression of the synaptic response at a 5 Hz stimulation frequency that was antagonized by the GABA(B) antagonist (2S)-3-[[(1S)-1-(3,4-dichlorophenyl)ethyl]amino-2-hydroxypropyl](phenylmethyl) phosphinic acid (CGP55845). The amplitude of the first IPSC during the 5 Hz stimulation was also increased by CGP55845, suggesting a tonic inhibition of synaptic transmission. A small unitary GABA(B)-mediated IPSC could also be detected, providing the first evidence for such a component between GABAergic interneurons. Electron microscopic localization of the GABA(B1) subunit at neurogliaform synapses revealed the protein in both presynaptic and postsynaptic membranes. Our data disclose a novel interneuronal network well suited for modulating the flow of information between the entorhinal cortex and CA1 hippocampus.

Alcohol Enhances GABAergic Transmission to Cerebellar Granule Cells via an Increase in Golgi Cell Excitability

Abstract: Alcohol intoxication alters coordination and motor skills, and this is responsible for a significant number of traffic accident-related deaths around the world. Although the precise mechanism of action of ethanol (EtOH) is presently unknown, studies suggest that it acts, in part, by interfering with normal cerebellar functioning. An important component of cerebellar circuits is the granule cell. The excitability of these abundantly expressed neurons is controlled by the Golgi cell, a subtype of GABAergic interneuron. Granule cells receive GABAergic input in the form of phasic and tonic currents that are mediated by synaptic and extrasynaptic receptors, respectively. Using the acute cerebellar slice preparation and patch-clamp electrophysiological techniques, we found that ethanol induces a parallel increase in both the frequency of spontaneous IPSCs and the magnitude of the tonic current. EtOH (50 mm) did not produce this effect when spontaneous action potentials were blocked with tetrodotoxin. Recordings in the loose-patch cell-attached configuration demonstrated that ethanol increases the frequency of spontaneous action potentials in Golgi cells. Taken together, these findings indicate that ethanol enhances GABAergic inhibition of granule cells via a presynaptic mechanism that involves an increase in action potential-dependent GABA release from Golgi cells. This effect is likely to have an impact on the flow of information through the cerebellar cortex and may contribute to the mechanism by which acute ingestion of alcoholic beverages induces motor impairment.

Distribution of prospective glutamatergic, glycinergic, and GABAergic neurons in embryonic and larval zebrafish.

Abstract: Zebrafish are an excellent model for studies of the functional organization of neuronal circuits, but little is known regarding the transmitter phenotypes of the neurons in their nervous system. We examined the distribution in spinal cord and hindbrain of neurons expressing markers of transmitter phenotype, including the vesicular glutamate transporter (VGLUT) genes for glutamatergic neurons, the neuronal glycine transporter (GLYT2) for glycinergic neurons, and glutamic acid decarboxylase (GAD65/67) for GABAergic neurons. All three markers were expressed in a large domain in the dorsal two-thirds of spinal cord, with additional, more ventral expression domains for VGLUT2 and GAD/GABA. In the large dorsal domain, dual in situ staining showed that GLYT2-positive cells were intermingled with VGLUT2 cells, with no dual-stained neurons. Many of the neurons in the dorsal expression domain that were positive for GABA markers at embryonic stages were also positive for GLYT2, suggesting that the cells might use both GABA and glycine, at least early in their development. The intermingling of neurons expressing inhibitory and excitatory markers in spinal cord contrasted markedly with the organization in hindbrain, where neurons expressing a particular marker were clustered together to form stripes that were visible running from rostral to caudal in horizontal sections and from dorsomedial to ventrolateral in cross sections. Dual labeling showed that the stripes of neurons labeled with one transmitter marker alternated with stripes of cells labeled for the other transmitter phenotypes. The differences in the distribution of excitatory and inhibitory neurons in spinal cord versus hindbrain may be tied to differences in their patterns of development and functional organization. J. Comp. Neurol. 480:1–18, 2004. © 2004 Wiley-Liss, Inc.

Ultrastructural Localization of Full-Length trkB Immunoreactivity in Rat Hippocampus Suggests Multiple Roles in Modulating Activity-Dependent Synaptic Plasticity

Abstract: Neurotrophins acting at the trkB receptor have been shown to be important modulators of activity-dependent plasticity in the hippocampus, but the mechanisms underlying these effects are not yet well understood. To identify the cellular and subcellular targets of trkB ligands in the adult rat hippocampal formation, full-length trkB receptor immunoreactivity (trkB-IR) was localized using electron microscopy. trkB-IR was present in the glutamatergic pyramidal and granule cells. Labeling in these neurons appeared as discrete clusters and was primarily in axons, excitatory-type axon terminals, and dendritic spines and to a lesser extent in somata and dendritic shafts. trkB-IR was commonly found on the plasma membrane of dendritic spines, whereas in other subcellular regions trkB-IR was often intracellular. Labeling was strikingly dense within axon initial segments, suggesting extensive receptor trafficking. trkB-IR was not confined to pyramidal and granule cells. Dense trkB-IR was found in occasional interneuron axon initial segments, some axon terminals forming inhibitory-type synapses onto somata and dendritic shafts, and excitatory-type terminals likely to originate extrahippocampally. This suggests that trkB is contained in some GABAergic interneurons, neuromodulatory (e.g., cholinergic, dopaminergic, and noradrenergic) afferents, and/or glutamatergic afferents. These data indicate that full-length trkB receptor activation may modulate glutamatergic pathways of the trisynaptic circuit both presynaptically at axon terminals and initial segments and postsynaptically at dendritic spines and shafts. Signaling via catalytic trkB may also presynaptically affect inhibitory and modulatory neurons. A pan-trkB antibody labeled the same neuronal populations as the full-length-specific trkB antiserum, but the labels differed in density at various subcellular sites. These findings provide an ultrastructural foundation for further examining the mechanisms through which neurotrophins acting at trkB receptors contribute to synaptic plasticity.

GABAergic cells in the dentate gyrus appear to be local circuit and projection neurons.

Abstract: Immunocytochemical results indicate that GAD-positive neurons are found in the molecular and granule cell layers of the dentate gyrus as well as in the hilar region. GAD-positive cells in the molecular and granule cell layers are identified as various types of local circuit neurons. Most of the GAD-positive puncta found throughout the molecular layer and within the granule cell layer are interpreted as axon terminals of these neurons, including five types of basket cells. This interpretation is based on data that indicate the axons of basket cells form synapses with the somata and proximal dendrites of granule cells. The results in the hilus show that 60% of the hilar neurons are GAD-positive. Since previous studies have indicated that 80% of hilar neurons give rise to both associational and commissural pathways, many GABAergic neurons in the hilus are probably projection neurons. This finding is consistent with recent physiological data which suggest that commissural pathway stimulation directly inhibits granule cells. Therefore, GABAergic cells in the dentate gyrus appear to be both projection and local circuit neurons.