GLUTAMATE-DEPENDENT LONG-TERM PRESYNAPTIC CHANGES IN CORTICOSTRIATAL EXCITABILITY

We have previously shown that brief high frequency stimulation of the anteromedial prefrontal cortex induces a long-term decrease in excitab ility of the glutamatergic corticostriatal terminal field. In contrast , a long-term increase in presynaptic corticostriatal excitability may be induced by presenting two brief cortical tetanizing stimuli separa ted by 2-3 min such that the second tetanus coincides with a period of increased excitability elicited by the first.(34) In the present stud y, we examined the glutamate receptor subtypes involved in these long- term changes in presynaptic excitability. A specific glutamate recepto r antagonist was infused into the rat striatum 10-25 min prior to eith er a single or double cortical tetanic stimulation. To eliminate the p articipation of intrinsic striatal cells, a subset of animals received a striatal kainic acid lesion eight to 20 days before the recording e xperiment. Antagonists of the N-methyl-D-aspartate and metabotropic gl utamate receptor subtypes were effective in blocking the decrease in e xcitability induced by single cortical tetanic stimulation whereas an antagonist of the lpha-amino-3-hydroxy-5-methylisoxazole-4-propionic a cid/kainate receptor did not prevent the induction of a long-term redu ction in excitability. In contrast, each of these antagonists prevente d the induction of a long-term increase in excitability. These long-te rm modifications in excitability of the presynaptic glutamate axon ter minals appear to be induced by similar mechanisms to those postulated to operate in long-term potentiation and depression. These enduring ch anges in presynaptic excitability are likely to represent important me chanisms for the selective modification of information processing in t he striatum. (C) 1996 IBRO. Published by Elsevier Science Ltd.