Psychiatric and neurodevelopmental disorders may arise from anomalies in long-range neuronal connectivity downstream of pathologies in dendritic spines. However, the mechanisms that may link spine pathology to circuit abnormalities relevant to atypical behavior remain unknown. Using a mouse model to conditionally disrupt a critical regulator of the dendritic spine cytoskeleton, Arp2/3, we report here a molecular mechanism that unexpectedly reveals the interrelationship of progressive spine

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... ng, elevated frontal cortical excitation of pyramidal neurons, and striatal hyperdopaminergia within a cortical-to-midbrain circuit abnormality. The main symptomatic manifestations of this circuit abnormality are psychomotor agitation and stereotypical behaviors, which are relieved by antipsychotics. Moreover, antipsychotic-responsive locomotion can be directly mimicked in wildtype mice by optogenetic activation of this circuit. Collectively these Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: