# Toward mechanistic cognitive neuroscience: cell types, connectivity, and patterned perturbations

> **NIH NIH DP1** · HARVARD MEDICAL SCHOOL · 2020 · $1,183,000

## Abstract

Summary
The cognitive functions of the brain allow higher animals to interact with the world in complex and adaptive
manners. For example, animals use past experiences to develop internal models of rules and contexts that
shape subsequent decisions. These cognitive processes are disrupted in many devastating mental health
disorders. Traditional experiments in cognitive neuroscience have identified correlations between cognitive
processes and behavioral outputs or neural events. However, it has been challenging to uncover the causal
mechanisms by which cognitive processes emerge from the basic building blocks of neurobiological
computations: molecules, cells, synapses, and circuits. The reason is, in large part, because it has been difficult
to combine emerging mechanistic approaches in neuroscience with paradigms to study cognitive processes.
Here we aim to overcome these challenges by developing a research program to identify causal links between
cognitive processes and the structure – cell types and connectivity – and function – spatiotemporal activity
patterns in neural populations – of neural circuits. We recently devised a virtual reality system for mice and
developed methods to train mice to perform complex, cognitive tasks as they navigate through virtual
environments. Further, we developed neurophysiological and computational tools that have identified correlates
of cognitive processes in the activity patterns in population of neurons. We will use this foundation to establish a
research program for mechanistic cognitive neuroscience. First, we will develop an atlas of cell types in cognitive
brain regions, use viral tools to label these cell types, and then study the functional roles of these cell types
during flexible decision-making tasks. Second, we will establish methods based on single-neuron optogenetics
to reveal connectivity between identified cells during cognitive behaviors. Third, we will use calcium imaging to
‘read’ patterns of neural activity during cognitive tasks and will then ‘write’ and ‘erase’ these patterns using
patterned optogenetics to test sufficiency and necessity. We will study these structural and functional properties
in local populations of neurons (microcircuits) and across brain areas (mesocircuits). This work will expand the
emerging field of mechanistic cognitive neuroscience and develop a new research program toward the goal of
defining cognition and mental health in terms of core biological components and mechanisms.

## Key facts

- **NIH application ID:** 10011969
- **Project number:** 1DP1MH125776-01
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Christopher D Harvey
- **Activity code:** DP1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,183,000
- **Award type:** 1
- **Project period:** 2020-09-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10011969

## Citation

> US National Institutes of Health, RePORTER application 10011969, Toward mechanistic cognitive neuroscience: cell types, connectivity, and patterned perturbations (1DP1MH125776-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10011969. Licensed CC0.

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