Disruption of neonatal Purkinje cell function underlies injury-related learning deficits

Proc Natl Acad Sci U S A. 2021 Mar 16;118(11):e2017876118. doi: 10.1073/pnas.2017876118.

Abstract

It is hypothesized that perinatal cerebellar injury leads to long-term functional deficits due to circuit dysmaturation. Using a novel integration of GCaMP6f fiber photometry with automated measurement of cerebellar behavior using the ErasmusLadder, we causally link cerebellar injury to altered Purkinje cell responses during maladaptive behavior. Chemogenetic inhibition of neonatal Purkinje cells is sufficient to phenocopy the effects of perinatal cerebellar injury. Our results uncover a direct link between perinatal cerebellar injury and activity-dependent maturation of cerebellar cortex.

Keywords: Purkinje cell; adaptive behavior; cerebellum; locomotor learning; neonatal brain injury.

Publication types

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

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Animals, Newborn
  • Cerebellar Diseases / complications*
  • Learning Disabilities / etiology*
  • Learning Disabilities / physiopathology*
  • Locomotion
  • Mice
  • Mice, Inbred C57BL
  • Purkinje Cells / pathology*