Is neuronal inhibition or excitability controlled by Na + K + 2CL – transporters?

2021 ◽  
Author(s):  
Andrea Ebersberger
Keyword(s):  
Neuronal Inhibition

Halothane enhances tonic neuronal inhibition of elevating intracellular calcium

1991 ◽  
Vol 538 (2) ◽  
pp. 319-323 ◽  
Author(s):  
Istvan Mody ◽  
Darrell L. Tanelian ◽  
M. Bruce MacIver
Keyword(s):  
Intracellular Calcium ◽  
Neuronal Inhibition

Decreased neuronal inhibition in vitro after long-term administration of ethanol

Science ◽  
1984 ◽  
Vol 224 (4655) ◽  
pp. 1359-1361 ◽  
Author(s):  
D Durand ◽  
P. Carlen
Keyword(s):  
Neuronal Inhibition ◽  
Term Administration

Abstract W MP41: Potentiation of Gaba-Mediated Synaptic Inhibition in the Recovery Phase: A Novel Therapeutic Target for Stroke

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Takeshi Hiu ◽  
Tonya Bliss ◽  
Jeanne Paz ◽  
Eric Wang ◽  
Zoya Farzampour ◽  
...  
Keyword(s):  
Pyramidal Cells ◽  
Recovery Phase ◽  
Synaptic Activity ◽  
Stroke Recovery ◽  
Functional Changes ◽  
Post Stroke ◽  
Array Tomography ◽  
Neuronal Inhibition ◽  
Gaba Signaling ◽  
Novel Therapeutic

Background: Stroke is a major cause of disability yet pharmacotherapy targeting the recovery phase is lacking. Cortical circuit reorganization adjacent to the stroke site promotes recovery, thus elucidating mechanisms that promote this plasticity could lead to new therapeutics. Tonic neuronal inhibition, mediated by extrasynaptic GABA A receptors,inhibits post-stroke recovery. However, effects of phasic (synaptic) GABA signaling - which promotes plasticity during development - are unknown. Here we use a combined approach of i) array tomography to determine the composition of GABA synapses in the post-stroke mouse brain, ii) electrophysiology to determine whether stroke leads to functional changes in GABA-mediated phasic inhibition, and (iii) treatment with zolpidem, an FDA-approved GABA agonist, to modulate recovery. Results: We found, using array tomography, a 1.7-fold increase in the number of GABAergic synapses containing the α1 receptor subunit in layer 5 of the peri-infarct cortex (synapse number/μm 3 : 0.039±0.006 (control) vs 0.064±0.006 (stroke); P<0.01), but not in layer 2/3. There was an associated increase in spontaneous inhibitory post-synaptic currents (sIPSC) specific to layer 5 pyramidal neurons (sIPSC charge (fC): -403±27.8 (control) vs -724±166 (stroke); p=0.03). This effect was transient, occurring during the onset of functional recovery. To test whether the increased phasic inhibitory GABAergic signaling promotes stroke recovery, we treated animals with zolpidem, an agonist with high affinity for α1 subunit-containing GABA A receptors. Low dose zolpidem increased GABA A phasic signaling in layer 5 pyramidal cells and notably increased the rate and extent of behavioral recovery without altering infarct size. Conclusions: These data provide the first evidence that enhanced GABA A -mediated synaptic activity during the recovery phase improves stroke outcome. These data identify modulation of phasic GABA signaling as a novel therapeutic strategy for stroke, indicate zolpidem as a potential drug to improve recovery, and underscore the necessity to distinguish the role of tonic and phasic GABA inhibition in stroke recovery.

Modulation of respiration during brain hypoxia

1990 ◽  
Vol 68 (2) ◽  
pp. 441-451 ◽  
Author(s):  
J. A. Neubauer ◽  
J. E. Melton ◽  
N. H. Edelman
Keyword(s):  
Animal Models ◽  
Respiratory Depression ◽  
Cellular Metabolism ◽  
Oxygen Availability ◽  
Cellular Systems ◽  
Respiratory Neuron ◽  
Brain Hypoxia ◽  
Cellular Basis ◽  
Neuronal Inhibition ◽  
Limited Oxygen

This review is a summary of the effects of brain hypoxia on respiration with a particular emphasis on those studies relevant to understanding the cellular basis of these effects. Special attention is given to mechanisms that may be responsible for the respiratory depression that appears to be the primary sequela of brain hypoxia in animal models. Although a variety of potential mechanisms for hypoxic respiratory depression are considered, emphasis is placed on changes in the neuromodulator constituency of the respiratory neuron microenvironment during hypoxia as the primary cause of this phenomenon. Hypoxia is accompanied by a net increase in neuronal inhibition due to both decreased excitatory and increased inhibitory neuromodulator levels. A survey of hypoxia-tolerant cellular systems and organisms suggests that hypoxic respiratory depression may be a manifestation of the depression of cellular metabolism, which appears to be a major adaptation to limited oxygen availability in these systems.

scholarly journals A light-gated potassium channel for sustained neuronal inhibition

2018 ◽  
Vol 15 (11) ◽  
pp. 969-976 ◽  
Author(s):  
Laura Alberio ◽  
Andrea Locarno ◽  
Andrea Saponaro ◽  
Edoardo Romano ◽  
Valérie Bercier ◽  
...  
Keyword(s):  
Potassium Channel ◽  
Neuronal Inhibition

scholarly journals Levetiracetam Induced Behavioral Abnormalities in a Patient with Seizure Disorder: A Diagnostic Challenge

2020 ◽  
Vol 2020 ◽  
pp. 1-4 ◽  
Author(s):  
Oluwaseun Ogunsakin ◽  
Terence Tumenta ◽  
Scarlet Louis-Jean ◽  
Ayesha Mahbub ◽  
Peterson Rabel ◽  
...  
Keyword(s):  
Side Effects ◽  
Adverse Effects ◽  
High Risk Patient ◽  
Seizure Disorder ◽  
Drug Discontinuation ◽  
Diagnostic Challenge ◽  
Behavioral Abnormalities ◽  
Neuronal Inhibition ◽  
Titration Period ◽  
High Index Of Suspicion

Levetiracetam is a second-generation antiepileptic drug that is chemically unrelated to other antiepileptic drugs. Levetiracetam is a broad-spectrum antiseizure medication that is approved as an adjunctive therapy in the treatment of partial and generalized tonic-clonic seizures in children and adults with epilepsy. The mechanism by which Levetiracetam induces behavioral changes remains unknown. Its proposed mechanism of action involves binding to synaptic vesicle protein 2A (SV2A) and this leads to neuronal inhibition. Though, the drug has a convenient dosing regimen and is relatively well tolerated, neuropsychiatric side effects can emerge beyond the initial titration period and may be the most common reason for drug discontinuation. Levetiracetam has been reported to cause varying degrees of psychiatric adverse effects including behavioral disturbance such as agitation, hostility and psychosis, and mood symptoms and suicidality. It has been shown to induce psychiatric side effects in 13.3% of adults, with only 0.7% presenting with severe symptoms such as depression, agitation, or hostility. The prevalence rate of development of psychosis in these patients is estimated to be about 1.4%. A review of literature has demonstrated a relative correlation between Levetiracetam use and the development of neurobehavioral symptoms which is increased in predisposed individuals. This research describes the case of a 28-year-old woman with seizure disorder and a psychiatric history of schizoaffective disorder who developed aggressive behavior, paranoia, and severe hostility following administration of Levetiracetam 750 mg orally twice daily. She developed acute behavioral symptoms which were reversed with cessation of Levetiracetam. This report emphasizes the need for developing an appropriately high index of suspicion in promoting surveillance and prompt identification of behavioral adverse effects associated with Levetiracetam especially in high-risk patient population.

scholarly journals Developmental cell death regulates lineage-related interneuron-oligodendroglia functional clusters and oligodendrocyte homeostasis

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
David Orduz ◽  
Najate Benamer ◽  
Domiziana Ortolani ◽  
Eva Coppola ◽  
Lisa Vigier ◽  
...  
Keyword(s):  
Cell Death ◽  
Precursor Cells ◽  
Synaptic Connectivity ◽  
Gabaergic Interneurons ◽  
Oligodendrocyte Precursor Cells ◽  
Related Cell ◽  
Neuronal Inhibition ◽  
Embryonic Origin ◽  
Oligodendrocyte Precursor ◽  
Developmental Cell Death

Abstract The first wave of oligodendrocyte precursor cells (firstOPCs) and most GABAergic interneurons share common embryonic origins. Cortical firstOPCs are thought to be replaced by other OPC populations shortly after birth, maintaining a consistent OPC density and making postnatal interactions between firstOPCs and ontogenetically-related interneurons unlikely. Challenging these ideas, we show that a cortical firstOPC subpopulation survives and forms functional cell clusters with lineage-related interneurons. Favored by a common embryonic origin, these clusters display unexpected preferential synaptic connectivity and are anatomically maintained after firstOPCs differentiate into myelinating oligodendrocytes. While the concomitant rescue of interneurons and firstOPCs committed to die causes an exacerbated neuronal inhibition, it abolishes interneuron-firstOPC high synaptic connectivity. Further, the number of other oligodendroglia populations increases through a non-cell-autonomous mechanism, impacting myelination. These findings demonstrate unprecedented roles of interneuron and firstOPC apoptosis in regulating lineage-related cell interactions and the homeostatic oligodendroglia density.

scholarly journals Compromising the phosphodependent regulation of the GABAAR β3 subunit reproduces the core phenotypes of autism spectrum disorders

2015 ◽  
Vol 112 (48) ◽  
pp. 14805-14810 ◽  
Author(s):  
Thuy N. Vien ◽  
Amit Modgil ◽  
Armen M. Abramian ◽  
Rachel Jurd ◽  
Joshua Walker ◽  
...  
Keyword(s):  
Autism Spectrum Disorders ◽  
Fragile X ◽  
Repetitive Behavior ◽  
Autism Spectrum ◽  
Membrane Stability ◽  
Receptor Subtypes ◽  
Neuronal Inhibition ◽  
Spectrum Disorders ◽  
Spine Structure

Alterations in the efficacy of neuronal inhibition mediated by GABAA receptors (GABAARs) containing β3 subunits are continually implicated in autism spectrum disorders (ASDs). In vitro, the plasma membrane stability of GABAARs is potentiated via phosphorylation of serine residues 408 and 409 (S408/9) in the β3 subunit, an effect that is mimicked by their mutation to alanines. To assess if modifications in β3 subunit expression contribute to ASDs, we have created a mouse in which S408/9 have been mutated to alanines (S408/9A). S408/9A homozygotes exhibited increased phasic, but decreased tonic, inhibition, events that correlated with alterations in the membrane stability and synaptic accumulation of the receptor subtypes that mediate these distinct forms of inhibition. S408/9A mice exhibited alterations in dendritic spine structure, increased repetitive behavior, and decreased social interaction, hallmarks of ASDs. ASDs are frequently comorbid with epilepsy, and consistent with this comorbidity, S408/9A mice exhibited a marked increase in sensitivity to seizures induced by the convulsant kainic acid. To assess the relevance of our studies using S408/9A mice for the pathophysiology of ASDs, we measured S408/9 phosphorylation in Fmr1 KO mice, a model of fragile X syndrome, the most common monogenetic cause of ASDs. Phosphorylation of S408/9 was selectively and significantly enhanced in Fmr1 KO mice. Collectively, our results suggest that alterations in phosphorylation and/or activity of β3-containing GABAARs may directly contribute to the pathophysiology of ASDs.

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