Topics

Paradoxical network excitation by glutamate release from VGluT3 GABAergic interneurons.

07:00 EST 13th February 2020 | BioPortfolio

Summary of "Paradoxical network excitation by glutamate release from VGluT3 GABAergic interneurons."

In violation of Dale's principle several neuronal subtypes utilize more than one classical neurotransmitter. Molecular identification of vesicular glutamate transporter 3 and cholecystokinin expressing cortical interneurons (CCKVGluT3INTs) has prompted speculation of GABA/glutamate corelease from these cells for almost two decades despite a lack of direct evidence. We unequivocally demonstrate CCKVGluT3INT mediated GABA/glutamate cotransmission onto principal cells in adult mice using paired recording and optogenetic approaches. Although under normal conditions, GABAergic inhibition dominates CCKVGluT3INT signaling, glutamatergic signaling becomes predominant when glutamate decarboxylase (GAD) function is compromised. CCKVGluT3INTs exhibit surprising anatomical diversity comprising subsets of all known dendrite targeting CCK interneurons in addition to the expected basket cells, and their extensive circuit innervation profoundly dampens circuit excitability under normal conditions. However, in contexts where the glutamatergic phenotype of CCKVGluT3INTs is amplified, they promote paradoxical network hyperexcitability which may be relevant to disorders involving GAD dysfunction such as schizophrenia or vitamin B6 deficiency.

Affiliation

Journal Details

This article was published in the following journal.

Name: eLife
ISSN: 2050-084X
Pages:

Links

DeepDyve research library

PubMed Articles [9890 Associated PubMed Articles listed on BioPortfolio]

Consequences of VGluT3 deficiency on learning and memory in mice.

The aim of the present study was to test the hypothesis that vesicular glutamate transporter 3 (VGluT3) deficiency is associated with cognitive impairments. Male VGluT3 knockout (KO) and wild type (WT...

Glutamate/Gaba Co-Release Selectively Influences Postsynaptic Glutamate Receptors In Mouse Cortical Neurons.

Cultured rat cortical neurons co-expressing VGLUT1 and VGAT (mixed synapses) co-release Glu and GABA. Here, mixed synapses were studied in cultured mouse cortical neurons to verify whether in mice mix...

Thrombin induces Ca-dependent glutamate release from RPE cells mediated by PLC/PKC and reverse Na/Ca exchange.

We analyzed the molecular mechanisms leading to glutamate release from rat primary cultures of RPE cells, under isosmotic conditions. Thrombin has been shown to stimulate glutamate release from astroc...

GABAergic interneurons in epilepsy: More than a simple change in inhibition.

The pathophysiology of epilepsy has been historically grounded on hyperexcitability attributed to the oversimplified imbalance between excitation (E) and inhibition (I) in the brain. The decreased inh...

Amperometric measurements of cocaine cue and novel context-evoked glutamate and nitric oxide release in the nucleus accumbens core.

Cue-induced reinstatement of cocaine seeking after self-administration (SA) and extinction relies on glutamate release in the nucleus accumbens core (NAcore), which activates neuronal nitric oxide syn...

Clinical Trials [3155 Associated Clinical Trials listed on BioPortfolio]

PET/MRI Imaging of Glutamate Release in the Brain

Based on PET (18-PSS232) and MRI, glutamate release after N-acetylcystein challenge will be monitored in human brains.

Imaging GABAergic/Glutamatergic Drugs in Bipolar Alcoholics Alcoholics

The proposed 3-week, double-blind, crossover, proof of concept study aims to manipulate neurochemical dysfunctions characteristic of individuals with co-occurring BD and AUD (i.e., abnorma...

Imaging Glutamate Release From Alcohol

The goal of this research project is to determine the sensitivity of PET radioligands specific for targets in the glutamate system to an alcohol challenge.

The Safety and Efficacy of Neramexane in Patients With Moderate to Severe Alzheimer's Disease

Memory loss and difficulties with thinking associated with Alzheimer's disease may be due to chronic release of a brain chemical called glutamate. Glutamate helps transmit messages between...

Reversing Corticosteroid Induced Memory Impairment

Stress and corticosteroid exposure are associated with changes in both the human and animal hippocampus. An extensive literature suggests that corticosteroid-induced changes in the hippoca...

Medical and Biotech [MESH] Definitions

Substances used for their pharmacological actions on GABAergic systems. GABAergic agents include agonists, antagonists, degradation or uptake inhibitors, depleters, precursors, and modulators of receptor function.

A PYRIDOXAL PHOSPHATE-containing enzyme that catalyzes the transfer of a formyl group from L-GLUTAMATE to N-formimidoyl-L-glutamate and TETRAHYDROFOLATE. This enzyme may also catalyze formyl transfer from 5-formyltetrahydrofolate to L-GLUTAMATE. This enzyme was formerly categorized as EC 2.1.2.6.

Blockage of an artery due to passage of a clot (THROMBUS) from a systemic vein to a systemic artery without its passing through the lung which acts as a filter to remove blood clots from entering the arterial circulation. Paradoxical embolism occurs when there is a defect that allows a clot to cross directly from the right to the left side of the heart as in the cases of ATRIAL SEPTAL DEFECTS or open FORAMEN OVALE. Once in the arterial circulation, a clot can travel to the brain, block an artery, and cause a STROKE.

An enzyme that catalyzes the conversion of ATP, L-glutamate, and NH3 to ADP, orthophosphate, and L-glutamine. It also acts more slowly on 4-methylene-L-glutamate. (From Enzyme Nomenclature, 1992) EC 6.3.1.2.

A tetrameric calcium release channel in the SARCOPLASMIC RETICULUM membrane of SMOOTH MUSCLE CELLS, acting oppositely to SARCOPLASMIC RETICULUM CALCIUM-TRANSPORTING ATPASES. It is important in skeletal and cardiac excitation-contraction coupling and studied by using RYANODINE. Abnormalities are implicated in CARDIAC ARRHYTHMIAS and MUSCULAR DISEASES.

Quick Search


DeepDyve research library

Relevant Topics

Psychiatry
Psychiatry is the study of mental disorders and their diagnosis, management and prevention.  Conditions include schizophrenia, severe depression and panic disorders among others. There are pharmaceutical treatments as well as other therapies to help...

Nutrition
Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...


Searches Linking to this Article