TYROSINE KINASE-DEPENDENT SELECTION OF TRANSMITTER RESPONSES INDUCED BY NEURONAL CONTACT

TRANSMITTER receptors are localized to discrete cellular sites1 such t hat only those responses appropriate for a particular pattern of input s are activated2-4. How neurons select between synaptic and extrasynap tic responses during development is not understood. We have investigat ed how contact during synapse formation between identified leech neuro ns5-7 selectively suppresses the modulation of extrasynaptic channels by protein kinase C8-10. A microelectrode with an isolated membrane pa tch containing channels from an uninnervated target neuron was 'cramme d'11 into a similar cell contacted by a presynaptic partner. We report here that within a few minutes, the crammed channels were rendered in sensitive to activation of protein kinase C, demonstrating the action of a cytoplasmic signal. Treatment of the neurons with selective inhib itors of tyrosine kinases12, which are signalling molecules during nor mal and oncogenic cellular differentiation13,14, prevented the loss of channel modulation. Thus, tyrosine kinases mediate early functional c hanges during specific synapse formation that are induced by neuronal contact.