TY - JOUR T1 - Corticostriatal Plasticity Established by Initial Learning Persists After Behavioral Reversal JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0209-20.2021 SP - ENEURO.0209-20.2021 AU - Sanchari Ghosh AU - Anthony M Zador Y1 - 2021/02/04 UR - http://www.eneuro.org/content/early/2021/02/01/ENEURO.0209-20.2021.abstract N2 - The neural mechanisms that allow animals to adapt their previously learned associations in response to changes in the environment remain poorly understood. To probe the synaptic mechanisms that mediate such adaptive behavior, we trained mice on an auditory-motor reversal task, and tracked changes in the strength of corticostriatal synapses associated with the formation of learned associations. Using a ChR2-based electrophysiological assay in acute striatal slices, we measured the strength of these synapses after animals learned to pair auditory stimuli with specific actions. Here we report that the pattern of synaptic strength initially established by learning remains unchanged even when the task contingencies are reversed. Our findings reveal that synaptic changes associated with the initial acquisition of this task are not erased or over-written, and that behavioral reversal of learned associations may recruit a separate neural circuit. These results suggest a more complex role of the striatum in regulating flexible behaviors where activity of striatal neurons may vary given the behavioral contexts of specific stimulus-action associations.Significance We have established that learning a specific auditory-motor association establishes a distinct pattern of plasticity in the tonotopic projection from auditory cortex to auditory striatum in mice. The sign of this association can be read out postmortem, with nearly perfect fidelity, using electrophysiological measurements from a single acute brain slice. We then trained another cohort of mice to reverse this association after the initial training period, and measured the plasticity pattern in this circuit. Surprisingly, even after learning the new association successfully, the corticostriatal plasticity pattern represented the initial association, acquired over 2 weeks ago. Our results have implications for the role of corticostriatal plasticity in forming stimulus-action associations and understanding the neural basis of learning in adaptive behaviors. ER -