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GABAergic
About: GABAergic is a research topic. Over the lifetime, 9595 publications have been published within this topic receiving 473568 citations.
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TL;DR: It is reported that opioid inhibition of GABAergic synaptic currents in the PAG is controlled by a presynaptic voltage-dependent potassium conductance, and mechanisms account for the analgesic action of cyclooxygenase inhibitors in thePAG and their synergism with opioids.
Abstract: The midbrain region periaqueductal grey (PAG) is rich in opioid receptors and endogenous opioids and is a major target of analgesic action in the central nervous system. It has been proposed that the analgesic effect of opioids on the PAG works by suppressing the inhibitory influence of the neurotransmitter GABA (gamma-aminobutyric acid) on neurons that form part of a descending antinociceptive pathway. Opioids inhibit GABA-mediated (GABAergic) synaptic transmission in the PAG and other brain regions by reducing the probability of presynaptic neurotransmitter release, but the mechanisms involved remain uncertain. Here we report that opioid inhibition of GABAergic synaptic currents in the PAG is controlled by a presynaptic voltage-dependent potassium conductance. Opioid receptors of the mu type in GABAergic presynaptic terminals are specifically coupled to this potassium conductance by a pathway involving phospholipase A2, arachidonic acid and 12-lipoxygenase. Furthermore, opioid inhibition of GABAergic synaptic transmission is potentiated by inhibitors of the enzymes cyclooxygenase and 5-lipoxygenase, presumably because more arachidonic acid is available for conversion to 12-lipoxygenase products. These mechanisms account for the analgesic action of cyclooxygenase inhibitors in the PAG and their synergism with opioids.
478 citations
TL;DR: How these GABAergic neurons act to control the body and enteric muscles necessary for different behaviours is deduced on the basis of the ultrastructurally defined connectivity of the C. elegans nervous system.
Abstract: gamma-Aminobutyric acid (GABA) is the most abundant inhibitory neurotransmitter in vertebrates and invertebrates. GABA receptors are the target of anxiolytic, antiepileptic and antispasmodic drugs, as well as of commonly used insecticides. How does a specific neurotransmitter such as GABA control animal behaviour? To answer this question, we identified all neurons that react with antisera raised against the neurotransmitter GABA in the nervous system of the nematode Caenorhabditis elegans. We determined the in vivo functions of 25 of the 26 GABAergic neurons by killing these cells with a laser microbeam in living animals and by characterizing a mutant defective in GABA expression. On the basis of the ultrastructurally defined connectivity of the C. elegans nervous system, we deduced how these GABAergic neurons act to control the body and enteric muscles necessary for different behaviours. Our findings provide evidence that GABA functions as an excitatory as well as an inhibitory neurotransmitter.
475 citations
TL;DR: GA exposure mimics the effects of SE on mIPSC and tonic GABAA current amplitudes in granule cells, consistent with the model predictions, and provides a potential mechanism for the inhibitory loss that characterizes initiation of SE and for the pharmacoresistance to benzodiazepines.
Abstract: During status epilepticus (SE), GABAergic mechanisms fail and seizures become self-sustaining and pharmacoresistant. During lithiumpilocarpine-induced SE, our studies of postsynaptic GABA(A) receptors in dentate gyrus granule cells show a reduction in the amplitude of miniature IPSCs (mIPSCs). Anatomical studies show a reduction in the colocalization of the beta2/beta3 and gamma2 subunits of GABA(A) receptors with the presynaptic marker synaptophysin and an increase in the proportion of those subunits in the interior of dentate granule cells and other hippocampal neurons with SE. Unlike synaptic mIPSCs, the amplitude of extrasynaptic GABA(A) tonic currents is augmented during SE. Mathematical modeling suggests that the change of mIPSCs with SE reflects a decrease in the number of functional postsynaptic GABA(A) receptors. It also suggests that increases in extracellular [GABA] during SE can account for the tonic current changes and can affect postsynaptic receptor kinetics with a loss of paired-pulse inhibition. GABA exposure mimics the effects of SE on mIPSC and tonic GABA(A) current amplitudes in granule cells, consistent with the model predictions. These results provide a potential mechanism for the inhibitory loss that characterizes initiation of SE and for the pharmacoresistance to benzodiazepines, as a reduction of available functional GABA(A) postsynaptic receptors. Novel therapies for SE might be directed toward prevention or reversal of these losses.
465 citations
TL;DR: A Cerebellar mutant, cerebelless, is described, which lacks the entire cerebellar cortex in adults and results suggest that Ptf1a is involved in driving neural precursors to differentiate into GABAergic neurons in the cerebellum.
462 citations
TL;DR: Initial clinical evidence comes from the significantly enhanced antidepressant therapeutic response when eszopicole, an anxiolytic/hypnotic acting preferentially on α(2)/α(3) and α(1) GABA(A) receptors, was coadministered with an antidepressant.
459 citations