# Behavioral and mechanistic dissection of a cognitive thalamo-cortical network

> **NIH NIH R01** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2021 · $472,083

## Abstract

Abstract
Interactions between the cortex and thalamus are essential for sensation, action and cognition. Although the
role of the thalamus in sensory processing is well-studied, its role in cognition is just beginning to be
elucidated. This proposal will focus on the mediodorsal thalamus (MD), one of the largest thalamic nuclei of
the mammalian brain, in regulating prefrontal cortex (PFC) activity in cognitive control and flexibility. MD-PFC
interactions are known to be perturbed in schizophrenia, but therapeutic options are limited because the circuit
mechanisms underlying these interactions are unknown. In this proposal, we will test an overarching model
that the MD regulates PFC connectivity patterns to match the behavioral context through enhancement of
context-relevant activity patterns and suppression of context-irrelevant ones. Specifically, our model posits
that MD neurons generate context-specific signals by selectively strengthening PFC inputs that carry the basic
elements of these signals but do not encode the context explicitly. Two MD cell types appear to generate
such signals, one of which uses it to enhance context-congruent PFC activity while the other suppresses
context incongruent activity. Lastly, our model posits that these distinct thalamic effects are mediated by
different PFC circuit motifs, an excitatory/disinhibitory and an inhibitory, respectively. In Aim I, we will test the
hypothesis that MD neurons generate context-specific output based on context non-specific inputs from PFC.
In Aim II, we will test the hypothesis that the two MD functional cell types map onto distinct genetic types. In
Aim III, we will test the hypothesis that the two MD-dependent effects on PFC, enhancement and suppression
of activity patterns, are implemented by distinct local circuit motifs. Overall, our work should clarify the circuit
mechanisms by which the MD influences PFC activity, providing a starting point for examining their generality
across different task switching paradigms as well as relationship to higher order thalamus function more
broadly. Our work should also be relevant to central mission of the NIH in understanding mechanisms with
therapeutic potential.

## Key facts

- **NIH application ID:** 10101693
- **Project number:** 5R01MH120118-02
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Michael M Halassa
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $472,083
- **Award type:** 5
- **Project period:** 2020-02-15 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10101693

## Citation

> US National Institutes of Health, RePORTER application 10101693, Behavioral and mechanistic dissection of a cognitive thalamo-cortical network (5R01MH120118-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10101693. Licensed CC0.

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