Molecular layer interneurons shape the spike activity of cerebellar Purkinje cells

Sci Rep. 2019 Feb 11;9(1):1742. doi: 10.1038/s41598-018-38264-1.

Abstract

Purkinje cells receive synaptic input from several classes of interneurons. Here, we address the roles of inhibitory molecular layer interneurons in establishing Purkinje cell function in vivo. Using conditional genetics approaches in mice, we compare how the lack of stellate cell versus basket cell GABAergic neurotransmission sculpts the firing properties of Purkinje cells. We take advantage of an inducible Ascl1CreER allele to spatially and temporally target the deletion of the vesicular GABA transporter, Vgat, in developing neurons. Selective depletion of basket cell GABAergic neurotransmission increases the frequency of Purkinje cell simple spike firing and decreases the frequency of complex spike firing in adult behaving mice. In contrast, lack of stellate cell communication increases the regularity of Purkinje cell simple spike firing while increasing the frequency of complex spike firing. Our data uncover complementary roles for molecular layer interneurons in shaping the rate and pattern of Purkinje cell activity in vivo.

Publication types

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

MeSH terms

  • Action Potentials*
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Biomarkers
  • Immunohistochemistry
  • Interneurons / cytology
  • Interneurons / physiology*
  • Mice
  • Nerve Degeneration / genetics
  • Nerve Degeneration / metabolism
  • Purkinje Cells / cytology
  • Purkinje Cells / physiology*
  • Vesicular Inhibitory Amino Acid Transport Proteins / genetics
  • Vesicular Inhibitory Amino Acid Transport Proteins / metabolism
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Ascl1 protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • Biomarkers
  • Vesicular Inhibitory Amino Acid Transport Proteins
  • vesicular GABA transporter
  • gamma-Aminobutyric Acid