Synaptic Specializations Support Frequency-Independent Purkinje Cell Output from the Cerebellar Cortex

Cell Rep. 2016 Dec 20;17(12):3256-3268. doi: 10.1016/j.celrep.2016.11.081.


The output of the cerebellar cortex is conveyed to the deep cerebellar nuclei (DCN) by Purkinje cells (PCs). Here, we characterize the properties of the PC-DCN synapse in juvenile and adult mice and find that prolonged high-frequency stimulation leads to steady-state responses that become increasingly frequency independent within the physiological firing range of PCs in older animals, resulting in a linear relationship between charge transfer and activation frequency. We used a low-affinity antagonist to show that GABAA-receptor saturation occurs at this synapse but does not underlie frequency-invariant transmission. We propose that PC-DCN synapses have two components of release: one prominent early in trains and another specialized to maintain transmission during prolonged activation. Short-term facilitation offsets partial vesicle depletion to produce frequency-independent transmission.

Keywords: Purkinje cells; TPMPA; cerebellum; deep cerebellar nucleus; presynaptic; receptor saturation; recovery from depression; short-term facilitation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism*
  • Aging / physiology
  • Animals
  • Cerebellar Cortex / metabolism*
  • Cerebellar Cortex / physiology
  • Cerebellar Nuclei / metabolism
  • Cerebellar Nuclei / physiology
  • Mice
  • Purkinje Cells / metabolism*
  • Purkinje Cells / physiology
  • Receptors, GABA-A / metabolism*
  • Synapses / metabolism
  • Synapses / physiology
  • Synaptic Transmission / genetics
  • Synaptic Transmission / physiology


  • Receptors, GABA-A