| First Author | Kupferschmidt DA | Year | 2019 |
| Journal | J Neurosci | Volume | 39 |
| Issue | 8 | Pages | 1457-1470 |
| PubMed ID | 30559150 | Mgi Jnum | J:272496 |
| Mgi Id | MGI:6280526 | Doi | 10.1523/JNEUROSCI.1940-18.2018 |
| Citation | Kupferschmidt DA, et al. (2019) Active Zone Proteins RIM1alphabeta Are Required for Normal Corticostriatal Transmission and Action Control. J Neurosci 39(8):1457-1470 |
| abstractText | 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 RIM1alphabeta (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.SIGNIFICANCE STATEMENT Our daily functioning hinges on the ability to flexibly and efficiently learn and control our actions. How the brain encodes these capacities is unclear. Here we identified a selective role for presynaptic proteins RIM1alphabeta in controlling glutamate release from cortical inputs to the dorsolateral striatum, a brain structure critical for action learning and control. Behavioral analysis of mice with restricted genetic deletion of RIM1alphabeta further revealed roles for RIM1alphabeta-dependent processes in the learning and refinement of motor skills and the balanced expression of goal-directed and habitual actions. |
