SRC, N-METHYL-D-ASPARTATE (NMDA) RECEPTORS, AND SYNAPTIC PLASTICITY

The protein tyrosine kinase Src is expressed widely in the central ner vous system and is abundant in neurons. Over the past several years, e vidence has accumulated showing that one function of Src is to regulat e the activity of N-methyl-D-aspartate (NMDA) receptors and other ion channels. NMDA receptors are a principal subtype of glutamate receptor that mediates fast excitatory transmission at most central synapses. Recently it has been discovered that, by means of up-regulating the fu nction of NMDA receptors, Src mediates the induction of long-term pote ntiation (LTP) in the CA1 region of the hippocampus. This finding led to a new model for induction of LTP whereby tetanic stimulation produc es a rapid activation of Src, causing enhanced NMDA receptor function. This enhanced NMDA receptor function boosts the entry of Ca2+, which may thereby trigger the downstream signalling cascade, ending in poten tiation of non-NMDA receptors. This functional role for Src may be imp ortant in physiological and pathophysiological processes in the centra l nervous system. BIOCHEM PHARMACOL 56;7:789-798, 1998. (C) 1998 Elsev ier Science Inc.