Speaker: Ning Leow

Advisor: Prof. Mriganka Sur

Defense Date/Time: December 13th 2022, 10am-11am

In Person Loation: Picower Seminar Room, 46-3310

Virtual Location: https://mit.zoom.us/j/97818579978

Defense Title: 
Multiplexed representations of uncertainty by mouse pulvinar-prefrontal projections during goal-directed behaviors

Abstract:  Processing sensory information to generate decisions and action is a central component of learned, goal-directed behavior. Even during ongoing sensory-motor processing, our sensory landscape is filtered through our prior expectations and ongoing goals. This active perceptual process hinges on a distributed network of cortical and subcortical areas. The pulvinar, or homologous rodent lateral posterior (LP) nucleus, is a higher-order visual thalamic nucleus that bridges many of these subcortical and cortical structures. In particular, LP/pulvinar interactions with the prefrontal cortices such as the anterior cingulate cortex (ACC) have been implicated in regulating attentional processes. However, the anatomical inputs integrated and precise information carried by this projection during decision-making and action-selection has never been clarified. We address this gap by leveraging genetic tools available in mouse models to examine the role of LP-ACC inputs directly with projection-specific anatomical mapping, axonal calcium imaging with two-photon microscopy in animals viewing visual stimuli passively or performing a decision task, and opto-genetic manipulations. We find that LP-ACC axons integrate inputs from a vast network of subcortical and cortical structures that are implicated in attention, visuomotor functions, and spatial cognition. During passive viewing, activity of the LP-ACC projection is dominated by global arousal states while visual information is poorly represented. During a two-alternative graded random dot motion direction discrimination task, LP-ACC activity in individual axons and the axonal population represents multiple task variables. The activity of single axons ranges from the cod- ing of stimulus coherence and direction in the random dot stimuli to the signaling of different task epochs in individual trials. At the population level, we find highly structured representations of task variables: LP-ACC activity jointly represents direction and coherence of visual stimuli in a low-dimensional geometric manifold that facilitates visual decoding. Furthermore, LP-ACC axons dynamically represent the outcome and uncertainty of previous trials, and integrate past and current trial uncertainty throughout the task. These physiological responses influence trial-by-trial behavior, which can be disrupted by optogenetic perturbation of specific trial epochs. Our findings demonstrate that the LP contributes to attention and decision-making by providing a read-out of ongoing uncertainty, integrated over time with behavioral history, to adaptively tune neuronal responses and guide goal-directed behavior on a trial-to-trial basis.