Role of a non-classical amygdala striatal pathway in selection of instrumental actions

About This Grant

Project summary Living organisms need to interpret various sensory information and implement corresponding instrumental actions to maximize their chances of getting rewards. Alterations of the process of perceptual decision making are associated with several mental illnesses including schizophrenia and substance use disorders. Although both the amygdala and the striatum are implicated in reward seeking and selection of instrumental actions, the neural mechanisms of how these two structures work in concert to regulate sensory-driven decision making remain elusive. With neural tracing and endoscopic calcium imaging, I identified two anatomically and functionally distinct neural populations in the anterior and posterior basolateral amygdala (BLA) that differentially innervated the tail of the striatum (TS) and the nucleus accumbens (NAc). While the NAc projecting BLA neurons (BLANAc) primarily encoded reward acquisition, the TS projecting BLA neurons (BLATS) were activated during instrumental actions and further segregated into separate ensembles that encoded different action choices during perceptual decision making. Building on these findings, I propose to investigate the heterogeneity of BLA striatal projections and interrogate the mechanisms of how BLATS neurons instruct the selection of instrumental actions. In aim1, I will perform single-cell RNA sequencing and monosynaptic rabies tracing experiments to reveal the molecular and wiring principals that govern the BLA functional heterogeneity. In aim2, I hypothesize that choice-encoding BLATS neural ensembles selectively innervate the direct and indirect pathways in the TS to bias action choices. I will leverage the Targeted Recombination in Active Populations (TRAP) approach in combination with optogenetic assisted circuit mapping to test the causal role of biased connection between choice encoding BLATS neurons and the TS direct and indirect pathways in action selection. In aim3, I will test if BLATS neurons broadly control action selection in naturalistic behaviors. This proposal will expand our knowledge of the amygdala and striatum function and provide a mechanistic understanding of the process of perceptual decision making. The proposed research and career development plan will be conducted in the lab of Dr. Guoping Feng at McGovern Institute for Brain Research at MIT, which will prepare Dr. Xin Fu to direct an innovative research program as an independent investigator studying the synaptic and functional organization of neural circuits underlying decision making in reward-seeking behaviors.