Search results for "GABAergic"

Benzodiazepine receptor interactions may be involved in the neurotoxicity of various penicillin derivatives

1980

The interaction of seven penicillin derivatives with specific [3H]flunitrazepam binding to benzodiazepine receptors was investigated. The affinities of the penicillins for benzodiazepine receptor seemed to depend on the lipophilia of the derivatives. The concentrations of the penicillins which inhibit specific [3H]flunitrazepam binding are consistent with penicillin levels found in the central nervous system of patients developing penicillin induced convulsions. The results suggest that penicillins inhibit GABAergic transmission not only at the GABA receptor, but also at the benzodiazepine receptor, which is thought to be part of a neuronal system facilitating GABAergic transmission. Both m…

Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic inf…

2018

AbstractHumans vary substantially in their willingness to take risks. In a combined sample of over one million individuals, we conducted genome-wide association studies (GWAS) of general risk tolerance, adventurousness, and risky behaviors in the driving, drinking, smoking, and sexual domains. We identified 611 approximately independent genetic loci associated with at least one of our phenotypes, including 124 with general risk tolerance. We report evidence of substantial shared genetic influences across general risk tolerance and risky behaviors: 72 of the 124 general risk tolerance loci contain a lead SNP for at least one of our other GWAS, and general risk tolerance is moderately to stro…

Long-Term Behavioral Programming Induced by Peripuberty Stress in Rats Is Accompanied by GABAergic-Related Alterations in the Amygdala

2014

Stress during childhood and adolescence is a risk factor for psychopathology. Alterations in γ-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the brain, have been found following stress exposure and fear experiences and are often implicated in anxiety and mood disorders. Abnormal amygdala functioning has also been detected following stress exposure and is also implicated in anxiety and social disorders. However, the amygdala is not a unitary structure; it includes several nuclei with different functions and little is known on the potential differences the impact of early life stress may have on this system within different amygdaloid nuclei. We aimed here to evaluate pote…

Coincident glutamatergic depolarizations enhance GABAA receptor-dependent Cl- influx in mature and suppress Cl- efflux in immature neurons

2020

AbstractThe impact of GABAergic transmission on neuronal excitability depends on the Cl−-gradient across membranes. However, the Cl−-fluxes through GABAA receptors alter the intracellular Cl− concentration ([Cl−]i) and in turn attenuate GABAergic responses, a process termed ionic plasticity. Recently it has been shown that coincident glutamatergic inputs significantly affect ionic plasticity. Yet how the [Cl−]i changes depend on the properties of glutamatergic inputs and their spatiotemporal relation to GABAergic stimuli is unknown. To investigate this issue, we used compartmental biophysical models of Cl− dynamics simulating either a simple ball-and-stick topology or a reconstructed immatu…

Development of the GABAergic system from birth to adolescence.

2011

The neurotransmitter GABA (γ-aminobutyric acid), acting via inotropic GABAA and metabotropic GABAB receptors, plays an essential role in a variety of distinct neuronal processes, including regulation of neuronal excitability, determination of temporal aspects of spike trains, control of the size and propagation of neuronal assemblies, generation of oscillatory activity, and neuronal plasticity. Although the developmental switch between excitatory and inhibitory GABAA receptor–mediated responses is widely appreciated, the fact that the postnatal maturation of the GABAergic system lasts until late adolescence is not so persuasively promoted. This review summarizes recent knowledge of the mat…

Lack of APP and APLP2 in GABAergic Forebrain Neurons Impairs Synaptic Plasticity and Cognition.

2020

AbstractAmyloid-β precursor protein (APP) is central to the pathogenesis of Alzheimer’s disease, yet its physiological functions remain incompletely understood. Previous studies had indicated important synaptic functions of APP and the closely related homologue APLP2 in excitatory forebrain neurons for spine density, synaptic plasticity, and behavior. Here, we show that APP is also widely expressed in several interneuron subtypes, both in hippocampus and cortex. To address the functional role of APP in inhibitory neurons, we generated mice with a conditional APP/APLP2 double knockout (cDKO) in GABAergic forebrain neurons using DlxCre mice. These DlxCre cDKO mice exhibit cognitive deficits i…

mGluR control of interneuron output regulates feedforward tonic GABAA inhibition in the visual thalamus

2011

Metabotropic glutamate receptors (mGluRs) play a crucial role in regulation of phasic inhibition within the visual thalamus. Here we demonstrate that mGluR-dependent modulation of interneuron GABA release results in dynamic changes in extrasynaptic GABAA receptor (eGABAAR)-dependent tonic inhibition in thalamocortical (TC) neurons of the rat dorsal lateral geniculate nucleus (dLGN). Application of the group I selective mGluR agonist dihydroxyphenylglycine produces a concentration-dependent enhancement of both IPSC frequency and tonic GABAA current (IGABAtonic) that is due to activation of both mGluR1a and mGluR5 subtypes. In contrast, group II/III mGluR activation decreases both IPSC freque…

The Endocannabinoid System as a Therapeutic Target in Epilepsy

2008

Perineuronal Net Formation and the Critical Period for Neuronal Maturation in the Hypothalamic Arcuate Nucleus

2019

In leptin-deficient ob/ob mice, obesity and diabetes are associated with abnormal development of neurocircuits in the hypothalamic arcuate nucleus (ARC)1, a critical brain area for energy and glucose homoeostasis2,3. Because this developmental defect can be remedied by systemic leptin administration, but only if given before postnatal day 28, a critical period for leptin-dependent development of ARC neurocircuits has been proposed4. In other brain areas, critical-period closure coincides with the appearance of perineuronal nets (PNNs), extracellular matrix specializations that restrict the plasticity of neurons that they enmesh5. Here we report that in humans and rodents, subsets of neurons…

Malformations of Cortical Development and Neocortical Focus

2014

Abstract Developmental neocortical malformations resulting from abnormal neurogenesis, disturbances in programmed cell death, or neuronal migration disorders may cause a long-term hyperexcitability. Early generated Cajal–Retzius and subplate neurons play important roles in transient cortical circuits, and structural/functional disorders in early cortical development may induce persistent network disturbances and epileptic disorders. In particular, depolarizing GABAergic responses are important for the regulation of neurodevelopmental events, like neurogenesis or migration, while pathophysiological alterations in chloride homeostasis may cause epileptic activity. Although modern imaging tech…