T-Cell Receptor Activation Decreases Excitability of Cortical Interneurons by Inhibiting alpha 7 Nicotinic Receptors

Many proteins in the immune system are also expressed in the brain. One such class of immune proteins are T-cell receptors (TCRs), whose functions in T lymphocytes in adaptive immunity are well characterized. In the brain, TCRs are confined to neocortical neurons, but their functional role has not b...

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Bibliographic Details
Published in:The Journal of neuroscience 2014-01, Vol.34 (1), p.22-35
Main Authors: Komal, Pragya, Gudavicius, Geoff, Nelson, Christopher J, Nashmi, Raad
Format: Article
Language:English
Online Access:Get full text
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Summary:Many proteins in the immune system are also expressed in the brain. One such class of immune proteins are T-cell receptors (TCRs), whose functions in T lymphocytes in adaptive immunity are well characterized. In the brain, TCRs are confined to neocortical neurons, but their functional role has not been determined. In mouse layer 1 neocortical neurons, TCR activation inhibited alpha 7 nicotinic currents. TCRs modulated alpha 7 currents via tyrosine phosphorylation of alpha 7 nicotinic receptors (nAChRs) through src tyrosine kinases because eliminating lck kinase expression, coexpressing fyn kinase dead, or mutating tyrosine to alanine in alpha 7 blocked the effect of TCR activation. We found that TCR stimulation decreased surface alpha 7 nAChRs and reduced single-channel conductance. These results reveal that TCRs play a major role in the modulation of cholinergic neurotransmission in the brain mediated by alpha 7 nAChRs and that this has a profound effect on regulating neuronal excitability.
ISSN:0270-6474
1529-2401
DOI:10.1523/JNEUROSCI.2093-13.2014