Tyrosine kinase-dependent selection of transmitter responses induced by neuronal contact

Abstract

TRANSMITTER receptors are localized to discrete cellular sites¹ such that only those responses appropriate for a particular pattern of inputs are activated^2–4. How neurons select between synaptic and extrasynaptic responses during development is not understood. We have investigated how contact during synapse formation between identified leech neurons^5–7 selectively suppresses the modulation of extrasynaptic channels by protein kinase C^8–10. A microelectrode with an isolated membrane patch containing channels from an uninnervated target neuron was 'crammed'¹¹ into a similar cell contacted by a presynaptic partner. We report here that within a few minutes, the crammed channels were rendered insensitive to activation of protein kinase C, demonstrating the action of a cytoplasmic signal. Treatment of the neurons with selective inhibitors of tyrosine kinases¹², which are signalling molecules during normal and oncogenic cellular differentiation^13,14, prevented the loss of channel modulation. Thus, tyrosine kinases mediate early functional changes during specific synapse formation that are induced by neuronal contact.