Search results for "GABAergic"

Modelling the spatial and temporal constrains of the GABAergic influence on neuronal excitability

2021

GABA (γ-amino butyric acid) is an inhibitory neurotransmitter in the adult brain that can mediate depolarizing responses during development or after neuropathological insults. Under which conditions GABAergic membrane depolarizations are sufficient to impose excitatory effects is hard to predict, as shunting inhibition and GABAergic effects on spatiotemporal filtering of excitatory inputs must be considered. To evaluate at which reversal potential a net excitatory effect was imposed by GABA (EGABAThr), we performed a detailed in-silico study using simple neuronal topologies and distinct spatiotemporal relations between GABAergic and glutamatergic inputs. These simulations revealed for GABAe…

GABA-A Receptors Regulate Neocortical Neuronal Migration In Vitro and In Vivo

2006

The cortical migration process depends on a number of trophic factors and on the activation of different voltage- and ligand-gated channels. We investigated the role of gamma-aminobutyric acid (GABA) type A receptors in the neuronal migration process of the newborn rat parietal cortex in vivo and in vitro. Local in vivo application of the GABA-A antagonist bicuculline methiodide (BMI) or the agonist muscimol via cortical surface Elvax implants induced prominent alterations in the cortical architecture when compared with untreated or sham-operated controls. BMI- and muscimol-treated animals revealed heterotopic cell clusters in the upper layers and a complete loss of the cortical lamination …

Effect of depolarizing GABAA-mediated membrane responses on excitability of Cajal-Retzius cells in the immature rat neocortex

2011

In immature neurons activation of ionotropic GABA receptors induces depolarizing membrane responses due to a high intracellular Cl− concentration ([Cl−]i). However, it is difficult to draw conclusions about the functional consequences of subthreshold GABAergic depolarizations, since GABAergic membrane shunting and additional effects on voltage-dependent ion channels or action potential threshold must be considered. To systematically investigate factors that determine the GABAergic effect on neuronal excitability we performed whole cell patch-clamp recordings from Cajal-Retzius cells in immature rat neocortex, using [Cl−]i between 10 and 50 mM. The effect of focal GABA application was quant…

GABAergic projections from the subplate to Cajal-Retzius cells in the neocortex.

2011

Subplate neurons and Cajal-Retzius cells play an important role in the corticogenesis. Despite morphological evidence, the question whether subplate neurons innervate Cajal-Retzius cells has not been studied yet. We report that electrical stimulation in the subplate resulted in evoked GABAergic inhibitory postsynaptic currents (eIPSCs) in Cajal-Retzius cells. The eIPSC latency showed minor variability and amounted to approximately 4 ms, suggesting the monosynaptic connection. During the first postnatal week: (i) eIPSC amplitude increased, (ii) eIPSC kinetics sped up, (iii) the size of readily releasable pool increased, and (iv) γ-aminobutyric acid release probability decreased. We conclude …

Structure-activity relationship of furosemide-derived compounds as antagonists of cerebellum-specific GABA(A) receptors.

1998

The Na+-K+-2Cl- cotransporter blocker furosemide inhibits gamma-aminobutyric acid (GABA)-gated chloride currents and reverses GABA-mediated inhibition of [35S]-t-butylbicyclophosphorothionate ([35S]TBPS) binding of the cerebellar alpha6 subunit-containing GABA(A) receptors much more potently than the cerebrocortical non-alpha6 subunit-containing receptors. Of the 44 compounds studied, all precursors or derivatives of diuretics, one compound [hydrazinosulfonyl-furosemide (PF 1885)] reversed 5-microM GABA-induced inhibition of [35S]TBPS binding to cerebellar and cerebrocortical receptors. Three other compounds, all of which are structurally closely related to furosemide, were selective antago…

GABA and GABA receptors in the gastrointestinal tract: from motility to inflammation

2015

Although an extensive body of literature confirmed γ-aminobutyric acid (GABA) as mediator within the enteric nervous system (ENS) controlling gastrointestinal (GI) function, the true significance of GABAergic signalling in the gut is still a matter of debate. GABAergic cells in the bowel include neuronal and endocrine-like cells, suggesting GABA as modulator of both motor and secretory GI activity. GABA effects in the GI tract depend on the activation of ionotropic GABAA and GABAC receptors and metabotropic GABAB receptors, resulting in a potential noteworthy regulation of both the excitatory and inhibitory signalling in the ENS. However, the preservation of GABAergic signalling in the gut …

Valproate and GABAergic system effects.

2003

Phasic GABAA-receptor activation is required to suppress epileptiform activity in the CA3 region of the immature rat hippocampus

2012

Summary Purpose:  Despite the consistent observation that γ-aminobutyric acid A (GABAA) receptors mediate excitatory responses at perinatal stages, the role of the GABAergic system in the generation of neonatal epileptiform activity remains controversial. Therefore, we analyzed whether tonic and phasic GABAergic transmission had differential effects on neuronal excitability during early development. Methods:  We performed whole cell patch-clamp and field potential recordings in the CA3 region of hippocampal slices from immature (postnatal day 4–7) rats to analyze the effect of specific antagonists and modulators of tonic and phasic GABAergic components on neuronal excitability. Key Findings…

GABAC receptors are functionally expressed in the intermediate zone and regulate radial migration in the embryonic mouse neocortex

2010

Radial neuronal migration in the cerebral cortex depends on trophic factors and the activation of different voltage- and ligand-gated channels. To examine the func- tional role of GABAC receptors in radial migration we ana- lyzed the effects of specific GABAA and GABAC receptor antagonists on the migration of BrdU-labeled neurons in vitro using organotypic neocortical slice cultures. These experi- ments revealed that the GABAA specific inhibitor bicuculline methiodide facilitated neuronal migration, while the GABAC specific inhibitor (1,2,5,6-tetrahydropyridine-4-yl) methylphos- phinic-acid (TPMPA) impeded migration. Co-application of TPMPA and bicuculline methiodide or the unspecific ionot…

Functional Hallmarks of GABAergic Synapse Maturation and the Diverse Roles of Neurotrophins

2011

Functional impairment of the adult brain can result from deficits in the ontogeny of GABAergic synaptic transmission. Gene defects underlying autism spectrum disorders, Rett’s syndrome or some forms of epilepsy, but also a diverse set of syndromes accompanying perinatal trauma, hormonal imbalances, intake of sleep-inducing or mood-improving drugs or, quite common, alcohol intake during pregnancy can alter GABA signaling early in life. The search for therapeutically relevant endogenous molecules or exogenous compounds able to alleviate the consequences of dysfunction of GABAergic transmission in the embryonic or postnatal brain requires a clear understanding of its site- and state-dependent …