Ionotropic and metabotropic components of electrophysiological response of cerebellar Purkinje neurons to excitatory amino acids

Abstract

Cerebellar Purkinje neurons possess AMPA(( RS)-α-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid)-sensitive ionotropic glutamate receptors (AMPA GluRs) and ACPD((1S,3 R)-1-aminocyclopentane-1,3-dicarboxylic acid)-sensitive metabotropic glutamate receptors (mGluRs). The contributions of these receptors to responses elicited by dual receptor activation in cultured cerebellar Purkinje neurons were delineated by quantitative analysis of agonist-induced single unit activity. Responses to co-activation using Quis or AMPA + ACPD were biphasic, consisting of a dramatic increase in firing rate (excitatory phase) followed by a temporary 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 responses produced by selective activation of AMPA GluRs and mGluRs revealed that: (a) AMPA GluRs mediated the dramatic changes in firing rate, (b) mGluRs mediated the dramatic increases in bursting and the extended duration of each phase and (c) these AMPA GluR and mGluR mediated effects were largely additive when simultaneously activated. Nevertheless, interactions did occur with repeated co-activation of AMPA GluRs and mGluRs, as indicated by selective changes in the mGluR-mediated bursting component of the response. Such modulation may contribute to synaptic regulation of Purkinje neuron excitability, for example, that associated with long term depression.