Simple spike patterns and synaptic mechanisms encoding sensory and motor signals in Purkinje cells and the cerebellar nuclei

Neuron. 2024 Jun 5;112(11):1848-1861.e4. doi: 10.1016/j.neuron.2024.02.014. Epub 2024 Mar 15.

Abstract

Whisker stimulation in awake mice evokes transient suppression of simple spike probability in crus I/II Purkinje cells. Here, we investigated how simple spike suppression arises synaptically, what it encodes, and how it affects cerebellar output. In vitro, monosynaptic parallel fiber (PF)-excitatory postsynaptic currents (EPSCs) facilitated strongly, whereas disynaptic inhibitory postsynaptic currents (IPSCs) remained stable, maximizing relative inhibitory strength at the onset of PF activity. Short-term plasticity thus favors the inhibition of Purkinje spikes before PFs facilitate. In vivo, whisker stimulation evoked a 2-6 ms synchronous spike suppression, just 6-8 ms (∼4 synaptic delays) after sensory onset, whereas active whisker movements elicited broadly timed spike rate increases that did not modulate sensory-evoked suppression. Firing in the cerebellar nuclei (CbN) inversely correlated with disinhibition from sensory-evoked simple spike suppressions but was decoupled from slow, non-synchronous movement-associated elevations of Purkinje firing rates. Synchrony thus allows the CbN to high-pass filter Purkinje inputs, facilitating sensory-evoked cerebellar outputs that can drive movements.

Keywords: cerebellum; complex spike; motor command; prediction; sensorimotor; whisker.

MeSH terms

  • Action Potentials* / physiology
  • Animals
  • Cerebellar Nuclei* / cytology
  • Cerebellar Nuclei* / physiology
  • Excitatory Postsynaptic Potentials / physiology
  • Inhibitory Postsynaptic Potentials / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Purkinje Cells* / physiology
  • Synapses* / physiology
  • Vibrissae / physiology