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.

Highlights

  • The cerebellum is essential for diverse motor functions including coordination, learning, posture, and balance[1]

  • We targeted the function of the vesicular GABA transporter (VGAT), a transporter that is essential for the uptake of GABA into synaptic vesicles

  • We targeted the removal of the Vgat gene in stellate cells and basket cells in the cerebellar cortex by using the Mash1/Ascl[1] promoter to drive tamoxifen-inducible Cre in the cerebellum (Fig. 1d)[21]

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Summary

Introduction

The cerebellum is essential for diverse motor functions including coordination, learning, posture, and balance[1]. Genetic deletion using Ascl1CreER allowed us to independently target newly differentiated stellate cell and basket cell interneurons in the molecular layer because these neurons are born at different stages of cerebellar development, and intriguingly almost exclusively during the peri- to post-natal period when the cerebellar circuits are wiring up for function[24]. This is advantageous for our study because in vitro studies showed that as development progresses, interneuron to Purkinje cell inhibition increases[25]. We genetically mark stellate cells and basket cells independently and manipulate their GABAergic neurotransmission as the cells are born to determine their impact on establishing the mature firing properties of Purkinje cells in vivo

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