T-Cell Receptor Activation Decreases Excitability of Cortical Interneurons by Inhibiting α7 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 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.