Candelabrum cells are ubiquitous cerebellar cortex interneurons with specialized circuit properties

Tomas Osorno, Stephanie Rudolph, Tri Nguyen, Velina Kozareva, Naeem M. Nadaf, Aliya Norton, Evan Z. Macosko, Wei Chung Allen Lee, Wade G. Regehr

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)702-713
Number of pages12
JournalNature Neuroscience
Volume25
Issue number6
DOIs
StatePublished - Jun 2022

ASJC Scopus subject areas

  • Neuroscience(all)

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