The research described here investigates the role played by inhibitory processes in the discriminations made by the nervous system of humans and animals between familiar and unfamiliar and significant and nonsignificant events. This research compared the effects of two inhibitory mediators of gamma-aminobutyric acid (GABA): 1) phenibut, a nonselective agonist of ionotropic GABA(A) and metabotro...

Circuitry of the cerebellar cortex is regionally and functionally specialized. Unipolar brush cells (UBCs), Purkinje cell (PC) synapses made by axon collaterals in granular layer, are both enriched areas that control balance eye movement. Here, we find a link between these specializations mice: PCs preferentially inhibit metabotropic glutamate receptor type 1 (mGluR1)-expressing UBCs respond to...

The neutral amino acid gamma-aminobutyric acid (GABA) produced membrane hyperpolarization and increased membrane chloride ion conductance of spinal cord (SC) and cortical (CTX) neurons in cell culture. GABA dose-response curves were obtained for SC neurons by pressure applying known concentrations of GABA from micropipettes with large tips (miniperfusion pipettes). GABA response threshold was a...

Characteristics of ionotropic gamma-aminobutyric acid (GABA) receptors at bullfrog cone terminals were studied by patch clamp techniques in isolated cell and retinal slice preparations. GABA-induced inward currents from isolated cones reversed in polarity at a potential, very close to the chloride equilibrium potential, and they were completely suppressed by picrotoxin. Unexpectedly, the GABA c...

Phosphorylation can affect both the function and trafficking of GABA(A) receptors with significant consequences for neuronal excitability. Serine/threonine kinases can phosphorylate the intracellular loops between M3-4 of GABA(A) receptor beta and gamma subunits thereby modulating receptor function in heterologous expression systems and in neurons (1, 2). Specifically, CaMK-II has been demonstr...

GABA receptors (GABA(A)) are the major sites of fast synaptic inhibition in the brain and can be assembled from five subunit classes: alpha, beta, gamma, delta, and epsilon. Receptor function can be regulated by direct phosphorylation of beta and gamma2 subunits, but how kinases are targeted to GABA(A) receptors is unknown. Here we show that protein kinase C-betaII (PKC-betaII) is capable of di...

AIMS Hypnotic zolpidem is a positive allosteric modulator of γ-aminobutyric acid (GABA) action, with preferential although not exclusive binding for α1 subunit-containing GABA(A) receptors. The pharmacological profile of this drug is different from that of classical benzodiazepines, although it acts through benzodiazepine binding sites at GABA(A) receptors. The aim of this study was to further ...

GABA(A) receptor channels are ubiquitous in the mammalian central nervous system mediating fast inhibitory neurotransmission by becoming permeant to chloride ions in response to GABA. The emphasis of this review is on the rich chemical diversity of ligands that influence GABA(A) receptor function. Such diversity provides many avenues for the design and development of new chemical entities actin...

The consequences of sustained activation of GABA(B) receptors on GABA(B)-mediated inhibition and network activity were investigated in the neonatal rat hippocampus using whole-cell and extracellular field recordings. GABA(B)-mediated presynaptic control of gamma-aminobutyric acid (GABA) release progressively diminished with time in spite of the continued presence of the agonist (100 microM bacl...