# P4: Multiregion interactions

> **NIH NIH U19** · PRINCETON UNIVERSITY · 2024 · $685,433

## Abstract

Project Summary/Abstract: Project 4, Multi-Region Interactions
 So far, our U19 program has largely focused on how individual brain regions support working memory
and decision-making. While this work has identiﬁed a large network of regions that contribute to
decision-making, we now need to understand how these regions interact with each other. What information is
sent between which regions, and when? How does such interaction depend on task demands? This project’s
goal is to address these gaps by combining cutting-edge recording methods, recordings during cell-type-
speciﬁc perturbations, new computational methods, and a panel of decision-making tasks.
 We propose to collect two datasets of multi-region, large-scale, cellular-resolution recordings (Aim 1).
In the ﬁrst, we will record simultaneously from a large network of regions, using next-generation Neuropixels
NXT technology. In the second, we will image simultaneously from three regions with our mesoscope while
obtaining cell-type-speciﬁc information through Core 4, Neuroanatomy. For both datasets, we will apply new
methods that we have developed to estimate time-dependent information ﬂow across regions.
 In addition to this broad, large-scale survey, we will perform two more targeted experiments. In the
basal ganglia, we will address the puzzle of how perturbation of neural activity that is not choice selective can
nevertheless lead to choice biases, by combining cell-type-specific perturbations with downstream recordings
(Aim 2). We will also address the broad and recently prominent question of the cerebellum’s role in cognition
(Van Overwalle 2020; Wagner 2020; Stoodley 2021). By manipulating cerebellar populations while recording in
thalamus and cortex, we will test the hypothesis that, by analogy to the cerebellum’s role in refining and
stabilizing motor trajectories, this region also serves to refine and stabilize neural trajectories in frontal
association areas (Aim 3).
 Taken together, we expect that these experimental and computational approaches will provide the
foundation for a multi-region description of how decisions are formed, which will provide important
constraints for our multi-region mechanistic model in Project 5. This work will substantially advance three
priority areas of the BRAIN Initiative: the brain in action, demonstrating causality, and identifying fundamental
principles.

## Key facts

- **NIH application ID:** 10900688
- **Project number:** 5U19NS132720-02
- **Recipient organization:** PRINCETON UNIVERSITY
- **Principal Investigator:** Ilana Witten
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $685,433
- **Award type:** 5
- **Project period:** 2023-08-08 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10900688

## Citation

> US National Institutes of Health, RePORTER application 10900688, P4: Multiregion interactions (5U19NS132720-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10900688. Licensed CC0.

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