Tyrosine phosphorylation-dependent inhibition of hippocampal synaptic plasticity

We examined the effects of two protein tyrosine phosphatase inhibitors on t he induction of synaptic plasticity in CAI slices of rat hippocampus. Field potential recordings were made in stratum radiatum in response to stimulat ion of the Schaffer collateral afferents. Bath application of the tyrosine phosphatase inhibitors sodium orthovanadate or phenylarsine oxide for 30 mi n had little effect on basal synaptic transmission but blocked the inductio n of both long-term potentiation (LTP) and homosynaptic long-term depressio n (LTD). LTP could be partially recovered, and LTD fully recovered, when co nditioning stimulation was given in conditions of reduced synaptic inhibiti on. The block of both forms of synaptic plasticity by the phosphatase inhib itors correlated with a concurrent depression of the N-methyl-D-aspartate ( NMDA) receptor-mediated potential, as measured both extracellularly and int racellularly. This depression, which was also induced by peroxyvanadate, re quired synaptic stimulation to be induced, and was tyrosine kinase-dependen t. Our results suggest that tyrosine phosphorylation of as yet unidentified proteins is responsible for a novel activity-dependent depression of NMDA receptor function that inhibits synaptic plasticity. (C) 2000 Elsevier Scie nce Ltd. All rights reserved.