Candelabrum cells are ubiquitous cerebellar cortex interneurons with specialized circuit properties

• Published in: Nature neuroscience Vol. 25; no. 6; pp. 702 - 713
• Main Authors: Osorno, Tomas, Rudolph, Stephanie, Nguyen, Tri, Kozareva, Velina, Nadaf, Naeem M., Norton, Aliya, Macosko, Evan Z., Lee, Wei-Chung Allen, Regehr, Wade G.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-06-2022; Nature Publishing Group
• Subjects: 14/28; 14/32; 14/69; 38/39; 631/378/1697; 631/378/3920; 64/110; 64/60; 9/74; Animal Genetics and Genomics; Animals; Behavioral Sciences; Biological Techniques; Biomedical and Life Sciences; Biomedicine; Cerebellar Cortex - physiology; Cerebellum; Cerebellum - physiology; Circuits; Cortex; Electron microscopy; Electrophysiology; Gene sequencing; Granule cells; High resistance; Hybridization; Interneurons; Interneurons - physiology; Mice; Microscopy; Morphology; Neural networks; Neurobiology; Neurons; Neurons - physiology; Neurosciences; Purkinje Cells - physiology; Synapses; γ-Aminobutyric acid
• DOI: 10.1038/s41593-022-01057-x
• EISSN: 1546-1726
• ISSN: 1097-6256; 1546-1726

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.
Candelabrum cells have remained an obscure cerebellar cell type. The authors show that candelabrum cells are the most abundant Purkinje layer interneuron, are molecularly distinct and have a connectivity that allows them to control cerebellar output.