SYNAPTIC EXCITATION OF INDIVIDUAL RAT CEREBELLAR GRANULE CELLS IN-SITU - EVIDENCE FOR THE ROLE OF NMDA RECEPTORS

1. Current-clamp recordings were made in whole-cell patch-clamp config uration from ninety one granule cells in parasagittal cerebellar slice s obtained from 21- to 31-day-old rats. Recordings were performed at 3 0 degrees C. 2. Resting membrane potential was -58 +/- 6 mV (n = 43). The membrane voltage response to step current injection showed inward rectification consistent with increasing input resistance during membr ane depolarization. Over -35 +/- 7 mV (n = 14) repetitive firing with little or no adaptation was activated. Spike frequency increased nearl y linearly with injected current. 3. Unitary EPSPs obtained by stimula ting the messy fibre bundle had an amplitude of 11.4 +/- 2.1 mV (n = 2 2, holding potential = -75 mV). Synchronous activation of greater than one to two messy fibres was needed to elicit action potentials. Antid romic stimulation elicited antidromic spikes and also EPSPs, presumabl y through a messy fibre 'axon reflex'. 4. EPSPs were brought about by NMDA and non-NMDA receptor activation, accounting for about 70 and 30% , respectively, of peak amplitude at the holding potential of -70 mV. The EPSP decay conformed to passive membrane discharge after blocking the NMDA receptors. 5. No appreciable correlation was found between th e time-to-peak and decay time constant of the EPSPs, consistent with t he compact electrotonic structure of these neurons. 6. During membrane depolarization EPSP amplitude increased transiently, due to both a vo ltage-dependent increase of the NMDA component and inward rectificatio n. In addition, EPSPs slowed down due to a slowdown of the NMDA compon ent. 7. Temporal summation during high-frequency stimulation was susta ined by NMDA receptors, whose contribution to depolarization tended to prevail over that of non-NMDA receptors during the trains. A block of the NMDA receptors resulted in reduced depolarization and output spik e frequency. 8. This study, as well as extending previous knowledge to the intracellular level in vivo, provides evidence for a primary role of NMDA receptors in determining messy fibre excitation of granule ce lls. It is suggested that the marked voltage dependence of the EPSP ti me course, which was mainly caused by voltage dependence in NMDA condu ctance, promotes the NMDA receptor-dependent enhancement of granule ce ll coding observed during repetitive messy fibre activity.