期刊
JOURNAL OF NEUROSCIENCE
卷 34, 期 1, 页码 22-35出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2093-13.2014
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资金
- 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
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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