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brainCOGS - circuits of COGnitive Systems. Carlos Brody. Mechanisms of neural circuit dynamics in working memory and decision-making

Abstract 3:

Title: Participation of Edinger-Westphal Nucleus as an attentional gate to accumulate visual evidence in head-fixed mice

Abstract: Many decisions require individuals to accumulate evidence and preserve it in memory to guide their decisions towards the obtention of desirable consequences. This evidence accumulation process requires multiple components: a gate that tells the brain when to start and stop accumulating the evidence, update the information, and retain it in memory until a decision is made. Despite extensive prior research on the neural correlates of visual evidence accumulation, no conclusion about which brain region might support the mechanisms to initiate or stop the accumulation has been achieved. Visual information from the optical nerve reaches the Edinger-Westphal Nucleus (EWN), a midbrain region whose activation and inhibition improves and impairs attention, respectively. However, the role of EWN as a gate to start visual evidence accumulation remains unanswered. To address this issue, we will optogenetically silence EWN while already-trained head-fixed mice are performing a flashes accumulation task. During the task, flashes will appear on either lateral side and, after a delay epoch, the mice are required to emit a response to the side with a higher number of flashes. EWN optosilencing will be performed during whole-trial, cue-epoch (accumulation), or delay-epoch (memory), or starting at different times during the cue epoch (gate) to assess if evidence-leakage/open-gate could be induced. Pupillometry, an attentional measurement, will be tracked to serve as a gate-closing indicator: when accumulation starts. The aforementioned together with a passive version of the task, where the reward will be delivered in either lateral spout despite the evidence, will allow us to dissect the contribution of motor vs. attentive pupil diameter changes. Electrophysiological recordings of EWN and simultaneous optoinactivation of EWN plus electrophysiological recordings of the visual cortex will be obtained.

Data type: Mice, behavior, optogenetics, electrophysiology.

Open questions: Identify the components (gate, accumulation, memory) of the accumulation process that are being affected during optogenetic perturbations, via modeling behavior. Implement a Drift Diffusion Model that incorporates attentional open-close gate to account for choice and bias. Determine if these components could be encoded by population dynamics (e.g., manifolds). Quantify the contribution of pupil diameter changes over single-unit and population neural activity encoding of accumulation and gate closing.

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