Ca currents activated by spontaneous firing and synaptic disinhibition in neurons of the cerebellar nuclei.

ABSTRACT: In neurons of the cerebellar nuclei, long-term potentiation of EPSCs is induced by high-frequency synaptic excitation by mossy fibers followed by synaptic inhibition by Purkinje cells. Induction requires activation of synaptic receptors as well as voltage-gated Ca channels. To examine how Purkinje-mediated inhibition of nuclear neurons affects Ca levels during plasticity-inducing stimuli, we have combined electrophysiology, Ca imaging, and pharmacology of cerebellar nuclear neurons in mouse cerebellar slices. We find that spontaneous firing generates tonic Ca signals in both somata and dendrites, which drop during 500 ms, 100 Hz trains of Purkinje IPSPs or hyperpolarizing steps. Although the presence of low-voltage-activated (T-type) Ca channels in nuclear neurons has fostered the inference that disinhibition activates these channels, synaptic inhibition with a physiological chloride equilibrium potential (E(Cl)) (-75 mV) fails to hyperpolarize neurons sufficiently for T-type channels to recover substantially. Consequently, after IPSPs, Ca signals return to baseline, although firing is accelerated by approximately 20 Hz for approximately 300 ms. Only after hyperpolarizations beyond E(Cl) does Ca rise gradually beyond baseline, as firing further exceeds spontaneous rates. Cd(2+) (100 microm), which nearly eliminates L-type, N-type, P/Q-type, and R-type Ca currents while sparing approximately one-half the T-type current, prevents Ca changes during and after hyperpolarizations to E(Cl). Thus, high-frequency IPSPs in cerebellar nuclear neurons evoke little postinhibitory current through T-type channels. Instead, inhibition regulates Ca levels simply by preventing action potentials, which usually permit Ca influx through high-voltage-activated channels. The decreases and restoration of Ca levels associated with Purkinje-mediated inhibition are likely to contribute to synaptic plasticity.

SUBMITTER: Zheng N 

PROVIDER: S-EPMC2746933 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature