# Flexible normalization in ferret V1: computational modeling and 2-photon imaging

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2021 · $477,754

## Abstract

ABSTRACT
The remarkable efficiency of human perception derives from the fact that we do not process each stimulus as a
novel event. Instead, past experiences and scene context inform internal, working models of the world that
allow us to generate predictions for our physical environment. A leading theory suggests that perceptual
predictions are accomplished via flexible normalization: local inhibitory neuronal populations are regulated by
long-range connections so that responses are suppressed when they do not provide helpful information about
object boundaries. However, the precise neural mechanisms by which the healthy human brain accomplishes
this flexible normalization are not known. In order to understand exactly how neural population responses are
suppressed or enhanced in response to different scene contexts, we will perform 2-photon imaging in ferret
primary visual cortex (V1) to quantify the responses of excitatory and inhibitory neural populations in superficial
layers of cortex during several different visual stimulus paradigms. The ferret model is chosen because the
imaging techniques necessary to quantify inhibitory neuronal responses are not yet well established in primate
models, and while our current knowledge about neural morphology and connections has been derived from
mouse models, mouse visual cortex lacks the “columnar organization” (spatial grouping of neurons with similar
response properties) that is a hallmark of primate visual cortex and is present in ferrets. Thus, the ferret model
is well-positioned to bridge the gap between mouse models and primate models. First, in order to understand
neuronal behaviors in the absence of contextual modulation, we will characterize interactions within a single
hypercolumn to small, simple stimuli (sinusoidally modulated luminance gratings) at a range of orientations and
contrasts. We hypothesize that parvalbumin-containing (PV+) inhibitory interneurons will demonstrate the
sharpest orientation tuning, followed by somatostatin-containing (SOM+) and serotonin-positive (5HTR+)
populations. Next. using a Cross Orientation Suppression paradigm, we will test the hypothesis that that SOM+
responses track the overall contrast energy in the stimulus, while PV+ populations reflect suppression of
individual grating component representations. Additional experiments with naturalistic textures will test whether
these behaviors generalize to stimuli with a broad range of contrasts, orientations, and spatial frequencies.
Finally, we will use classical Orientation-Dependent Surround Suppression and Collinear Facilitation paradigms
to study how the local inhibitory pool responds to scene context. We hypothesize that the responses of local
5HTR+ neurons will reflect the surrounding stimuli rather than the center stimuli. Together, these experiments
will constrain an open-source computational model articulated at the level of the single neuron that will
constrain hypotheses about how human perceptual beha...

## Key facts

- **NIH application ID:** 10299683
- **Project number:** 1R01NS123842-01
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** THEODEN I NETOFF
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $477,754
- **Award type:** 1
- **Project period:** 2021-08-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10299683

## Citation

> US National Institutes of Health, RePORTER application 10299683, Flexible normalization in ferret V1: computational modeling and 2-photon imaging (1R01NS123842-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10299683. Licensed CC0.

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