Cerebellar modulation of synaptic input to freezing-related neurons in the periaqueductal gray

Elife. 2020 Mar 24:9:e54302. doi: 10.7554/eLife.54302.

Abstract

Innate defensive behaviors, such as freezing, are adaptive for avoiding predation. Freezing-related midbrain regions project to the cerebellum, which is known to regulate rapid sensorimotor integration, raising the question of cerebellar contributions to freezing. Here, we find that neurons of the mouse medial (fastigial) cerebellar nuclei (mCbN), which fire spontaneously with wide dynamic ranges, send glutamatergic projections to the ventrolateral periaqueductal gray (vlPAG), which contains diverse cell types. In freely moving mice, optogenetically stimulating glutamatergic vlPAG neurons that express Chx10 reliably induces freezing. In vlPAG slices, mCbN terminals excite ~20% of neurons positive for Chx10 or GAD2 and ~70% of dopaminergic TH-positive neurons. Stimulating either mCbN afferents or TH neurons augments IPSCs and suppresses EPSCs in Chx10 neurons by activating postsynaptic D2 receptors. The results suggest that mCbN activity regulates dopaminergic modulation of the vlPAG, favoring inhibition of Chx10 neurons. Suppression of cerebellar output may therefore facilitate freezing.

Keywords: cerebellar nuclei; cerebellum; fastigial nucleus; fear; innate freezing; mouse; neuroscience; vlPAG.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Behavior, Animal
  • Cerebellum / physiology*
  • Female
  • Freezing Reaction, Cataleptic
  • Homeodomain Proteins / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neurons / physiology*
  • Optogenetics
  • Periaqueductal Gray / physiology*
  • Receptors, Dopamine / physiology
  • Reflex, Startle
  • Synapses / physiology*
  • Synaptic Potentials
  • Transcription Factors / physiology

Substances

  • Homeodomain Proteins
  • Receptors, Dopamine
  • Transcription Factors
  • Vsx2 protein, mouse