# Reversible activation of critical period plasticity in visual cortex

> **NIH NIH R01** · UNIV OF MARYLAND, COLLEGE PARK · 2024 · $68,151

## Abstract

Project Summary/Abstract
Amblyopia is induced in model systems by monocular deprivation (MD), which changes the stimulus selectivity
of neurons in the primary visual cortex. Prior research utilizing this model established that the changes in
neural selectivity induced by MD result from the reorganization of excitatory glutamatergic cortical synapses
onto excitatory cortical neurons, which is regulated by an inhibitory GABAergic network composed of
parvalbumin positive inhibitory interneurons (PV INs). An emerging consensus is that a permissive level of
inhibition from PV IN circuits in cortical layer 2/3 is required for plasticity at downstream excitatory synapses,
and that inhibition above or below the permissive range constrains the response to MD. Accordingly,
developmental strengthening of inhibition triggers the onset of the critical period; at later stages, the
“permissive” range of inhibition is achieved by reductions the recruitment of PV INs.
Here we identify the plasticity of excitation onto layer 2/3 PV INs as a critical locus for the regulation of circuit
reorganization in V1. Our preliminary data demonstrate that the initial response to MD is a rapid and transient
elimination of excitatory connections made by local pyramidal neurons (Pyr) onto PV INs. Following 1 day of
MD, we find that ~50% of local L2/3 PyràPV-IN connections are eliminated. Importantly, synapses from distal
L2/3 Pyrs and excitation from layer 4 Pyrs remains unchanged. This all-or-none elimination of specific
connections coincides with the loss of synaptic structure, is transient, and returns to control values following 3
days of MD. Our preliminary results also demonstrate that the MD-induced elimination of proximal L2/3
PyràPV INs inputs depends on mGluR5 activation and is inhibited by expression of activity-independent
neuronal pentraxin 2 (NPTX2). We propose that the rapid mGluR5 and NPTX2-dependent elimination of local
L2/3 PyràPV INs connection is an obligatory initial step for subsequent changes in ocular dominance and
spatial acuity induced by MD. Accordingly, we show that accumulation of NPTX2 prevents L2/3 PyràPV IN
elimination and ocular dominance plasticity. Conversely, expression of dominant negative NPTX2 in adults
reactivates the elimination of L2/3 PyràPV INs and ocular dominance plasticity in response to MD
We propose a series of multidisciplinary experiments to test the validity of this model that combine the
expertise of the Quinlan lab in the assessment of physiological changes in vivo physiology and the Kirkwood
lab in the assessment of changes in single synapses between identified neurons. We will test the hypothesis
that the elimination of L2/3 PyràPV INs excitatory synapses is 1) local, transient and confined to a postnatal
critical period 2) dependent on mGluR and NPTX2 signaling and 3) an obligatory initial step for subsequent
changes in ocular dominance and spatial acuity induced by MD. Our model predicts that the end of the critical...

## Key facts

- **NIH application ID:** 10953956
- **Project number:** 3R01EY025922-09S1
- **Recipient organization:** UNIV OF MARYLAND, COLLEGE PARK
- **Principal Investigator:** Alfredo Kirkwood
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $68,151
- **Award type:** 3
- **Project period:** 2015-09-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10953956

## Citation

> US National Institutes of Health, RePORTER application 10953956, Reversible activation of critical period plasticity in visual cortex (3R01EY025922-09S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10953956. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*