Active zone proteins RIM1∝β are required for normal corticostriatal transmission and action control

David A. Kupferschmidt, Shana M. Augustin, Kari A. Johnson, David M. Lovinger*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Dynamic regulation of synaptic transmission at cortical inputs to the dorsal striatum is considered critical for flexible and efficient action learning and control. Presynaptic mechanisms governing the properties and plasticity of glutamate release from these inputs are not fully understood, and the corticostriatal synaptic processes that support normal action learning and control remain unclear. Here we show in male and female mice that conditional deletion of presynaptic proteins RIM1∝β (RIM1) from excitatory cortical neurons impairs corticostriatal synaptic transmission in the dorsolateral striatum. Key forms of presynaptic G-protein-coupled receptor-mediated short-and long-term striatal plasticity are spared following RIM1 deletion. Conditional RIM1 KO mice show heightened novelty-induced locomotion and impaired motor learning on the accelerating rotarod. They further show heightened self-paced instrumental responding for food and impaired learning of a habitual instrumental response strategy. Together, these findings reveal a selective role for presynaptic RIM1 in neurotransmitter release at prominent basal ganglia synapses, and provide evidence that RIM1-dependent processes help to promote the refinement of skilled actions, constrain goal-directed behaviors, and support the learning and use of habits.

Original languageEnglish (US)
Pages (from-to)1457-1470
Number of pages14
JournalJournal of Neuroscience
Volume39
Issue number8
DOIs
StatePublished - Feb 20 2019
Externally publishedYes

Keywords

  • Action
  • Corticostriatal
  • Learning
  • Plasticity
  • RIM1
  • Transmission

ASJC Scopus subject areas

  • Neuroscience(all)

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