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 excitability 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 separated by 2-3 min such that the second tetanus coincides with a period of increased excitability elicited by the first. In the present study, we examined the glutamate receptor subtypes involved in these long-term changes in presynaptic excitability. A specific glutamate receptor antagonist was infused into the rat striatum 10-25 min prior to either a single or double cortical tetanic stimulation. To eliminate the participation of intrinsic striatal cells, a subset of animals received a striatal kainic acid lesion eight to 20 days before the recording experiment. Antagonists of the N-methyl-D-aspartate and metabotropic glutamate receptor subtypes were effective in blocking the decrease in excitability induced by single cortical tetanic stimulation whereas an antagonist of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid/kainate receptor did not prevent the induction of a long-term reduction in excitability. In contrast, each of these antagonists prevented the induction of a long-term increase in excitability. These long-term modifications in excitability of the presynaptic glutamate axon terminals appear to be induced by similar mechanisms to those postulated to operate in long-term potentiation and depression. These enduring changes in presynaptic excitability are likely to represent important mechanisms for the selective modification of information processing in the striatum.