Candelabrum cells are ubiquitous cerebellar cortex interneurons with specialized circuit properties

Nat Neurosci. 2022 Jun;25(6):702-713. doi: 10.1038/s41593-022-01057-x. Epub 2022 May 16.

Abstract

To understand how the cerebellar cortex transforms mossy fiber (MF) inputs into Purkinje cell (PC) outputs, it is vital to delineate the elements of this circuit. Candelabrum cells (CCs) are enigmatic interneurons of the cerebellar cortex that have been identified based on their morphology, but their electrophysiological properties, synaptic connections and function remain unknown. Here, we clarify these properties using electrophysiology, single-nucleus RNA sequencing, in situ hybridization and serial electron microscopy in mice. We find that CCs are the most abundant PC layer interneuron. They are GABAergic, molecularly distinct and present in all cerebellar lobules. Their high resistance renders CC firing highly sensitive to synaptic inputs. CCs are excited by MFs and granule cells and are strongly inhibited by PCs. CCs in turn primarily inhibit molecular layer interneurons, which leads to PC disinhibition. Thus, inputs, outputs and local signals converge onto CCs to allow them to assume a unique role in controlling cerebellar output.

Publication types

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

MeSH terms

  • Animals
  • Cerebellar Cortex* / physiology
  • Cerebellum / physiology
  • Interneurons* / physiology
  • Mice
  • Neurons / physiology
  • Purkinje Cells / physiology