# A dendritic nexus in the circuits that coordinate learning

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2024 · $363,939

## Abstract

Abstract
When we learn a complex behavior the nervous system must continuously drive new actions, compare
predictions for the actions against outcomes, and strengthen or weaken the connections between neurons
(synapses) in order to improve future actions. However, within the multilayer brain networks that control behavior,
the behavioral impact of modifying a synapse depends upon many downstream connections. Thus, learning
requires the brain solve a ‘credit assignment’ problem: information about which synaptic modifications should be
made is distributed across the network, yet must somehow be leveraged by local processes to guide change at
individual synapses. A major gap in our ability to relate behavioral events to synaptic change is the current lack
of knowledge of these local processes that guide synaptic changes at individual neurons. Recent theories of
learning suggest that spikes generated in the apical dendrites of cortical neurons may play a key role in solving
this credit assignment problem. The experiments in this proposal will test the hypothesis that the apical dendrites
of neurons in the pre-motor cortex integrate multiple learning-instructive feedback sources, and – under
appropriate conditions – generate dendritic spikes that rapidly reconfigure the connectivity and function of
neurons. In these experiments we will use advanced optical techniques to monitor and manipulate activity in the
dendrites of a subset of neurons in the frontal cortex that have a well-delineated role in action planning. A key
prediction of our hypothesis is that the activity of the apical dendrites reflects local credit-related calculations and
that this activity is distinct from the activity transmitted to other neurons by action potential generation near the
cell body. We will test this using longitudinal two-photon calcium imaging of cortical neurons during learning to
determine how the behavioral selectivity of dendrites and cell bodies change with changing behavior. In order to
identify the contribution of dendritic spikes to learning, we will also use optogenetics to selectively suppress
activity in the apical dendrites during learning. Computational models also predict that dendritic spikes are
generated by a mismatch between outcome information arriving from long-range feedback projections and local
inhibition that predicts this feedback. To test this, we will combine synaptic glutamate imaging and optogenetics
to map the selectivity and anatomical identity of feedback projections to the apical dendrites, and calcium imaging
to determine the selectivity of local inhibitory neurons that target the apical dendrites. Together, these studies
will provide critical new insights into the circuit mechanisms governing cortical plasticity and credit assignment.
In doing so, they will provide a key framework for connecting complex learning with modifications at the individual
synapse level, and will build bridges between machine learning algorithms and models ...

## Key facts

- **NIH application ID:** 10804735
- **Project number:** 5R01NS127902-02
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Aaron Michael Kerlin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $363,939
- **Award type:** 5
- **Project period:** 2023-04-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10804735

## Citation

> US National Institutes of Health, RePORTER application 10804735, A dendritic nexus in the circuits that coordinate learning (5R01NS127902-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10804735. Licensed CC0.

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