GABAergic

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

GABA expression dominates neuronal lineage progression in the embryonic rat neocortex and facilitates neurite outgrowth via GABA(A) autoreceptor/Cl- channels.

Abstract: GABA emerges as a trophic signal during rat neocortical development in which it modulates proliferation of neuronal progenitors in the ventricular/subventricular zone (VZ/SVZ) and mediates radial migration of neurons from the VZ/SVZ to the cortical plate/subplate (CP/SP) region. In this study we investigated the role of GABA in the earliest phases of neuronal differentiation in the CP/SP. GABAergic-signaling components emerging during neuronal lineage progression were comprehensively characterized using flow cytometry and immunophenotyping together with physiological indicator dyes. During migration from the VZ/SVZ to the CP/SP, differentiating cortical neurons became predominantly GABAergic, and their dominant GABAA receptor subunit expression pattern changed from α4β1γ1 to α3β3γ2γ3 coincident with an increasing potency of GABA on GABAA receptor-mediated depolarization. GABAA autoreceptor/Cl− channel activity in cultured CP/SP neurons dominated their baseline potential and indirectly their cytosolic Ca2+(Ca2+ c) levels via Ca2+ entry through L-type Ca2+channels. Block of this autocrine circuit at the level of GABA synthesis, GABAA receptor activation, intracellular Cl− ion homeostasis, or L-type Ca2+ channels attenuated neurite outgrowth in most GABAergic CP/SP neurons. In the absence of autocrine GABAergic signaling, neuritogenesis could be preserved by depolarizing cells and elevating Ca2+ c. These results reveal a morphogenic role for GABA during embryonic neocortical neuron development that involves GABAA autoreceptors and L-type Ca2+ channels.

Glutamic Acid Decarboxylase Messenger Ribonucleic Acid Is Regulated by Estradiol and Progesterone in the Hippocampus

Abstract: Ovarian steroids modulate learning, memory, and epileptic seizure activity, functions that are mediated in part by the hippocampus. Normal function depends on precise interactions between the inhibitory gamma-aminobutyric acid (GABA)ergic and excitatory glutamatergic neurons of the hippocampus. To determine whether estradiol and progesterone interact with GABAergic neurons, the levels of mRNA for glutamic acid decarboxylase (GAD), the rate-limiting enzyme for GABA synthesis, were measured by in situ hybridization histochemistry with 35S-labeled riboprobes complimentary to the feline GAD cDNA. The levels of mRNA for GAD were analyzed in selected region of the dorsal hippocampus and medial basal hypothalamus in ovariectomized, ovariectomized estradiol-treated, and ovariectomized estradiol- and progesterone-treated rats. In estradiol-treated rats, GAD mRNA levels increased in GABAergic neurons associated with the CA1 pyramidal cell layer, but not in the stratum oriens of CA1 or any other region of the hippoc...

Contribution of brainstem GABAergic circuitry to descending antinociceptive controls: I. GABA-immunoreactive projection neurons in the periaqueductal gray and nucleus raphe magnus.

Abstract: The fact that GABA receptor agonists and antagonists influence nociceptive thresholds when microinjected into the rostroventral medulla or in the spinal cord may reflect the involvement of GABAergic neuronal elements in endogenous antinociceptive pathways. In the present study we used immunocytochemistry and retrograde tract tracing to investigate the contribution of GABAergic projection neurons to the antinociceptive network linking the midbrain periaqueductal gray matter (PAG), the nucleus raphe magnus (NRM), and the spinal cord dorsal horn. The tracer, WGAapoHRP-Au was injected into either the NRM or the spinal cord and the distribution of labeled neurons in sections of the PAG and medulla, respectively, was studied. The same sections were immunostained to demonstrate GABA-immunoreactive neurons. Although GABA-immunoreactive neurons were abundant in the PAG, only 1.5% were retrogradely labeled from the NRM. Similarly, very few GABA-immunoreactive neurons within the cytoarchitectural boundaries of the NRM were retrogradely labeled from the spinal cord. A much higher proportion of GABA-immunoreactive neurons in the region lateral to the NRM, however, were retrogradely labeled from the spinal cord. Eighteen percent of GABA-immunoreactive neurons were retrogradely labeled in the nucleus reticularis paragigantocellularis; conversely, 15% of the retrogradely labeled neurons in this region were GABA-immunoreactive. These results indicate that GABAergic projections constitute a very minor component of the PAG-NRM-spinal cord pathway; however, there is a significant contribution of GABAergic neurons to the spinal projections that originate lateral to the NRM. The majority of GABAergic neurons in the PAG and NRM are presumed to be inhibitory interneurons that directly or indirectly regulate activity in efferent pathways from these regions.

Presynaptic P2X Receptors Facilitate Inhibitory GABAergic Transmission between Cultured Rat Spinal Cord Dorsal Horn Neurons

Abstract: The superficial layers of the spinal cord dorsal horn (DH) express P2X2, P2X4, and P2X6 subunits entering into the formation of ionotropic (P2X) receptors for ATP. Using a culture system of laminae I-III from neonatal rat DH, we show that ATP induced a fast nonselective cation current in 38% of the neurons (postsynaptic effect). ATP also increased the frequency of miniature IPSCs (mIPSCs) mediated by GABA(A) receptors or by glycine receptors in 22 and 9%, respectively, of the neurons tested (presynaptic effect) but had no effect on glutamatergic transmission. The presynaptic effect of ATP on GABAergic transmission was not significantly affected by thapsigargin (1 microM) but was completely dependent on Ca(2+) influx. Presynaptic and postsynaptic effects were inhibited by suramin, pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid, and reactive blue and were not reproduced by uridine 5'-triphosphate (UTP) or adenosine 5'-O-(2-thiodiphosphate) (ADP-beta-S), suggesting the implication of ionotropic P2X rather than of metabotropic P2Y receptors. alphabeta-methylene-ATP (100 microM) did not reproduce the effects of ATP. ATP reversibly increased the amplitude of electrically evoked GABAergic IPSCs and reduced paired-pulse inhibition or facilitation without affecting IPSC kinetics. This effect was preferentially, but not exclusively, observed in neurons coreleasing ATP and GABA. We conclude that in cultured DH neurons, the effects of ATP are mediated by P2X receptors having a pharmacological profile dominated by the P2X2 subunit. The presynaptic receptors might underlie a modulatory action of ATP on a subset of GABAergic interneurons involved in the spinal processing of nociceptive information.