The striatum is critical for learning and performance of goal-directed behaviors. This critical function is impaired in a number of neuropsychiatric disorders. The goal of the proposed studies is to establish a causal link between computations in striatal microcircuits and the learning and performance of goal directed behaviors. It is hypothesized that the feedforward inhibitory microcircuit in the striatum explicitly represents the proximity between self and goal, and uses this representation to command direction-specific velocity controllers downstream to generate the appropriate behavior. We will use an integrative approach combining wireless in vivo recording in awake behaving mice and 3D motion capture during continuous goal pursuit in freely moving mice.
Aim 1 will determine cell-type specific striatal representations underlying goal pursuit, using objective quantification of movement parameters in freely moving mice and in vivo recording of single unit activity.
Aim 2 will determine the causal contributions of specific circuit components during goal pursuit, using optogenetics to manipulate neural activity in defined neuronal populations bidirectionally. Finally, Aim 3 will quantify corticostriatal plasticity ex vivo following acquisition of goal-directed behavior, to determine the relationship between corticostriatal glutamatergic transmission and learning. Whole-cell patch clamp recordings will be done on brain slices from animals at different stages of training. Results from proposed studies will shed light on the computational functions of striatal microcircuits in acquiring and generating goal directed behaviors.
The capacity to pursue desired goals is a fundamental function of the brain. This capacity is impaired in neuropsychiatric disorders such as obsessive-compulsive disorder, schizophrenia, and autism. By expanding our knowledge of the striatal circuit mechanisms by which goal- directed behavior is acquired and generated, the proposed studies can lead to novel treatment strategies for diverse neuropsychiatric disorders.
|Tan, Shawn; Xiao, Yixin; Yin, Henry H et al. (2018) Postnatal TrkB ablation in corticolimbic interneurons induces social dominance in male mice. Proc Natl Acad Sci U S A 115:E9909-E9915|
|Bey, Alexandra L; Wang, Xiaoming; Yan, Haidun et al. (2018) Brain region-specific disruption of Shank3 in mice reveals a dissociation for cortical and striatal circuits in autism-related behaviors. Transl Psychiatry 8:94|
|Pappas, Andrea L; Bey, Alexandra L; Wang, Xiaoming et al. (2017) Deficiency of Shank2 causes mania-like behavior that responds to mood stabilizers. JCI Insight 2:|