Journal
JOURNAL OF NEUROSCIENCE
Volume 34, Issue 1, Pages 22-35Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2093-13.2014
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Funding
- Natural Sciences and Engineering Research Council of Canada Discovery grant
- Heart and Stroke Foundation of Canada grant
- National Alliance for Research on Schizophrenia and Depression Young Investigator Award
- Victoria Foundation-Myre and Winifred Sim Fund
- Canadian Foundation for Innovation grant
- British Columbia Knowledge Development Fund
- Natural Sciences and Engineering Research Council of Canada Research Tools and Instrumentation grant
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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 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.
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