Large-Scale Mapping of Striatal Dynamics during Perceptual Decision Making The accumulation of evidence over time is a critical aspect of many types of decision making in humans and animals. Recent work using optogenetic perturbation, supported by my preliminary data, shows that multiple subregions of the striatum are necessary for decisions requiring evidence accumulation. However, how encoding compares across these or other subregions of this large, heterogeneous structure is unknown. Furthermore, the striatum is interspersed with two types of projection neurons with distinct anatomical targets, whose specific role in evidence accumulation has not been studied. To constrain models describing how the brain carries out decision making, these critical knowledge gaps need to be filled. Specifically, it will be necessary to record systematically across striatal subregions and subtypes in an evidence accumulation paradigm, a task which has not been possible until very recently. Overcoming past technical hurdles, I will simultaneously record from hundreds of neurons spanning the entire striatum, along with surrounding input and output structures, by deploying a system we recently developed for chronic implantation of multiple, high-yield silicon (?Neuropixels?) probes in freely moving rats. Such recordings will be carried out at a set of nine targets sites densely tiling the striatum. Rats will perform a previously established task, highly amenable to quantitative analysis, requiring them to accumulate randomly timed pulses of auditory evidence (the ?Poisson Clicks? task). In a subset of these target sites, optogenetic tagging will be used in transgenic rats to identify recorded projection neurons based on their subtype (D1 or D2 dopamine receptor expression). These data will be the basis for a set of detailed functional maps describing how encoding for specific task variables (instantaneous and accumulated evidence, choice, reward, etc.) is distributed across striatal subregions and routed through the major striatal output pathways. I will use a generalized linear modeling (GLM) framework, that explicitly takes advantage of the pulsatile nature of the task, to disentangle and quantify the influence of these external covariates on neuronal firing rates. These data will provide a powerful new test for circuit models of the neural basis of evidence accumulation, and place important constraints on the distinct function of striatal pathways. Preliminary data has already yielded a novel finding: a hierarchy of evidence accumulation timescales in the dorsal striatum, with anterior areas integrating evidence for a decision over a relatively long timescale and posterior areas representing the instantaneous stimulus. This finding illustrates how the proposal will seize an opportunity to bring together multiple powerful techniques to yield new insights about the role of striatal subcircuits in decision making.
A core component of decision making is the accumulation of evidence over time, which depends on intact striatal function in animal models and goes awry in numerous brain disorders. However, the striatum is highly heterogeneous and it remains unclear how its role is mediated by distinct striatal subpopulations. To address this key clinically relevant gap, high-yield electrophysiological recordings will be combined with optogenetic tagging in rats to assess the role of striatal subregions and subtypes during evidence accumulation.
