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.