IONOTROPIC AND METABOTROPIC COMPONENTS OF ELECTROPHYSIOLOGICAL RESPONSE OF CEREBELLAR PURKINJE NEURONS TO EXCITATORY AMINO-ACIDS

Cerebellar Purkinje neurons possess AMPA pha-amino-3-hydroxyl-5-methyl -4-isoxazolepropionic acid)-sensitive ionotropic glutamate receptors ( AMPA GluRs) and ACPD ((1S,3R)-1-aminocyclopentane-1,3-dicarboxylic aci d)-sensitive metabotropic glutamate receptors (mGluRs). The contributi ons of these receptors to responses elicited by dual receptor activati on in cultured cerebellar Purkinje neurons were delineated by quantita tive analysis of agonist-induced single unit activity. Responses to co -activation using Quis or AMPA + ACPD were biphasic, consisting of a d ramatic increase in firing rate (excitatory phase) followed by a tempo rary decrease (inhibitory phase). In half of the cells tested bursting was induced during both the excitatory and inhibitory phases and the duration of each phase was prolonged relative to responses observed in non-bursting cells. Quantitative comparisons of these responses and r esponses produced by selective activation of AMPA GluRs and mGluRs rev ealed that: (a) AMPA GluRs mediated the dramatic changes in firing rat e, (b) mGluRs mediated the dramatic increases in bursting and the exte nded duration of each phase and (c) these AMPA GluR and mGluR mediated effects were largely additive when simultaneously activated. Neverthe less, interactions did occur with repeated co-activation of AMPA GluRs and mGluRs, as indicated by selective changes in the mGluR-mediated b ursting component of the response. Such modulation may contribute to s ynaptic regulation of Purkinje neuron excitability, for example, that associated with long term depression.