# Editing Population Codes For Action

> **NIH NIH DP2** · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · 2024 · $1,286,464

## Abstract

Project Summary
In the mammalian brain, action, perception, and cognition arise from the coordination of many neurons working
in concert. For decades, neuroscientists have observed these multi-neuron patterns of neural activity, and
developed complex ‘population codes’ to describe how a pattern correlates with a behavior. These population
codes make up our core understanding of how the brain works. However, simply observing activity cannot
distinguish between activity that drives a behavior (i.e., causality) vs that which only reports that a behavior
happened (i.e., correlation). Even modern optogenetic or chemogenetic approaches struggle to assess causality
in complex interconnected systems, like the mammalian cortex, and are incapable of testing the importance of
a pattern of activity, where information is encoded in the timing and relative firing rates of neurons. This has led
to calls for revised methodologies to study causality in neural systems. Here we leverage a unique and novel
approach, that we developed, to test the causal link between neural activity and specific actions. This new
approach enables the previously impossible task of recreating population activity de novo, writing different
numbers of action potentials into adjacent cells with millisecond precise timing. We will use this technique to ask
a fundamentally different class of questions than ever previously possible and create a framework determining
the causal role of population codes on behaviors.
Vector Optogenetics is the most advanced form of optogenetic stimulation yet, and the only approach able to
reproduce population activity. Evolving from multiphoton optogenetics, vector optogenetics allows a user to
specify not just which cells are activated but how many action potentials they will fire and when – anywhere
within the field of view of a conventional two-photon microscope and in a behaving mouse. In this proposal, we
use this technique to address several critical questions in motor cortex. Exploring, quantitatively, the nuance of
what patterns of activity drive specific behaviors, and other cells. We explore possible important features of a
population code (e.g., identity of activated cells, relative firing rates, synchrony, or sparsity of a pattern), as well
as popular theories of the importance of ‘low dimensional’ activity spaces. By combining vector optogenetics with
electrophysiology in the striatum, we further explore how patterns of activity drive downstream nuclei –
addressing questions about inter-area communication and the initiation of actions.
My experience as a systems neuroscientist, combined with being the inventor of these optical approaches,
makes me ideally suited to execute this plan, and overcome any obstacle. This proposal promises to
revolutionize how we study and validate models of cortical interaction and neural coding. Far from being limited
to motor control alone, these findings will have far-reaching implications – helping to create next-g...

## Key facts

- **NIH application ID:** 10908818
- **Project number:** 1DP2MH140135-01
- **Recipient organization:** RUTGERS BIOMEDICAL AND HEALTH SCIENCES
- **Principal Investigator:** Ian Anton Oldenburg
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,286,464
- **Award type:** 1
- **Project period:** 2024-09-10 → 2027-09-09

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10908818

## Citation

> US National Institutes of Health, RePORTER application 10908818, Editing Population Codes For Action (1DP2MH140135-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10908818. Licensed CC0.

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