# Optical interrogation of laminar microcircuit computations in mouse primary visual cortex

> **NIH NIH F31** · HARVARD MEDICAL SCHOOL · 2020 · $38,810

## Abstract

Project Summary/Abstract
A fundamental challenge of visual cortical neuroscience is to understand how sensory representations are
transformed within and across layers of primary visual cortex (V1). Visual signals are thought to propagate in a
feedforward manner from the thalamus through the layered structure of V1, from L4 (L4) to layer 2/3 (L2/3) to
layer 5. Here, we will address two major steps of visual processing: what are the mechanisms by which L4
transforms thalamic inputs, and how are representations transformed between L4 and L2/3? Recent studies in
mouse V1 suggest that L4 amplifies thalamocortical inputs, but the mechanisms by which such amplification
may occur, such as via local recurrent circuitry, have not been tested. Also, models from Hubel and Wiesel
proposed that the formation of complex receptive fields in L2/3 arises from the combination of L4 simple cell
inputs with similar orientation tuning and phase-offset subfields. Recent experimental work has shown
preferential connectivity between L4 and L2/3 neurons that are co-tuned for different visual features, providing
support for a potential mechanism by which selectivity is inherited. However, bridging the scales of anatomy and
activity measurements to reveal cortical transformations has previously been challenging due to a lack of
appropriate causal and functional methods. The goal of this proposal is to employ novel single-neuron resolution
in vivo optical approaches for causally perturbing and monitoring neural activity to understand computations
within and across layers during visual processing in awake animals. Our lab has developed a method, called
influence mapping, for simultaneous two-photon optogenetic photostimulation of targeted individual neurons
while imaging the responses of neighboring populations with known visual tuning properties. Aim 1 will use
influence mapping in L4 of V1 to test the hypothesis that recurrent connectivity in L4 amplifies visual signals via
a “like-excites-like” motif and determine whether such a motif is functionally operational for processing in different
visual stimulus regimes (i.e., low vs. high contrast). The studies outlined in Aim 2 will directly test whether L2/3
complex receptive fields are built from L4 simple cell inputs by photostimulating functionally defined L4 neurons
while imaging responses in L4 and L2/3. These experiments will advance our understanding of transformations
within and between layers in visual cortex. In addition, the new technical approaches developed may serve as a
foundation for future studies of laminar cortical mechanisms that underlie visual processing.

## Key facts

- **NIH application ID:** 9977407
- **Project number:** 1F31EY031562-01
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Anna Wang Jaffe
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $38,810
- **Award type:** 1
- **Project period:** 2020-09-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9977407

## Citation

> US National Institutes of Health, RePORTER application 9977407, Optical interrogation of laminar microcircuit computations in mouse primary visual cortex (1F31EY031562-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9977407. Licensed CC0.

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