bims-climfi Biomed News
on Cerebellar cortical circuitry
Issue of 2022–05–22
two papers selected by
Jun Maruta, Mount Sinai Health System
  1. Candelabrum cells are ubiquitous cerebellar cortex interneurons with specialized circuit properties.
  2. Granule cells constitute one of the major neuronal subtypes in the molecular layer of the posterior cerebellum.
  1. Nat Neurosci. 2022 May 16.
    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.
      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.
    DOI:  https://doi.org/10.1038/s41593-022-01057-x
  2. eNeuro. 2022 May 18. pii: ENEURO.0289-21.2022. [Epub ahead of print]
    Granule cells constitute one of the major neuronal subtypes in the molecular layer of the posterior cerebellum.
    Moushumi R Dey, Kirthan Reddy, Hiroichi Yoshida, Naoko Nishiyama, Boris Zemelman, Hiroshi Nishiyama.
      The migration of neurons from their birthplace to their correct destination is one of the most crucial steps in brain development. Incomplete or incorrect migration yields ectopic neurons, which cause neurological deficits or are negligible at best. However, the granule cells (GCs) in the cerebellar cortex may challenge this traditional view of ectopic neurons. When animals are born, GCs proliferate near the pia mater and then migrate down to the GC layer located deep in the cerebellar cortex. However, some GC-like cells stay in the molecular layer-a layer between the pia mater and GC layer-even in normal adult animals. These cells were named ectopic GCs nearly 50 years ago, but their abundance and functional properties remain unclear. Here, we have examined GCs in the molecular layer (mGCs) with a specific marker for mature GCs and transgenic mice in which GCs are sparsely labeled with a fluorescent protein. Contrary to the previous assumption that mGCs are a minor neuronal population, we have found that mGCs are as prevalent as stellate or basket cells in the posterior cerebellum. They are produced during a similar period as regular granule cells (rGCs), and in vivo time-lapse imaging has revealed that mGCs are stably present in the molecular layer. Whole-cell patch-clamp recordings have shown that mGCs discharge action potentials similarly to rGCs. Since axonal inputs differ between the molecular layer and GC layer, mGCs might be incorporated in different micro-circuits from rGCs and have a unique functional role in the cerebellum.Significance StatementDuring brain development, neurons migrate away from the place they are born to their correct destination. A defect in this process yields ectopic neurons, i.e., abnormally positioned neurons, which have been considered harmful and studied mostly in the context of brain diseases. Here, we show that abundant granule cells in the cerebellum are located ectopically in normal, healthy animals. These neurons are functionally mature and discharge action potentials similarly to conventional granule cells. The seemingly ectopic granule cells in the normal cerebellum may not be harmful or negligible. Rather, their abundance and distinct location suggest that they might play a unique functional role in the cerebellum via previously unconsidered neuronal connections.
    Keywords:  Cerebellum; Development; Ectopic neurons; Granule cells; Migration
    DOI:  https://doi.org/10.1523/ENEURO.0289-21.2022
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