# Stimulus competition and visuospatial selection: Neural circuit and computational mechanisms

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2024 · $457,561

## Abstract

PROJECT SUMMARY
Animals routinely operate in complex environments rich in sensory stimuli. They handle this informational
complexity by having their behavior guided by the most salient (and more generally, highest priority) stimulus in
the environment. The neural circuit mechanisms underlying competitive selection of the highest priority stimulus
across space remain poorly understood. Recent evidence from behaving monkeys has revealed that the
intermediate and deep layers of the superior colliculus (SCid), a major sensorimotor hub in the vertebrate
midbrain, are required for normal competitive stimulus selection. In parallel, our work in the barn owl optic tectum
(OTid, avian homolog of SCid) has revealed that OTid neurons signal the highest priority stimulus categorically,
which can account for SCid’s critical role in spatial selection behavior. Such categorical signaling requires a
specialized, donut-like pattern of spatial inhibition onto OTid from an inhibitory nucleus called Imc in the nearby
midbrain isthmic complex. Separately, feedback from a cholinergic isthmic nucleus, Ipc, is known to amplify OTid
firing rates. Despite these insights, several fundamental questions about the functional logic of this isthmo-tectal
(OT-Imc-Ipc) network for competitive stimulus selection remain open, and here, we address three. First, we aim
to elucidate how the preferential neural signaling of the most salient stimulus is implemented in OTid. Specifically,
our hypotheses are (1a) that OTid signals the strongest among competing stimuli with a combination of enhanced
gamma synchrony, reduced trial-trial variability, greater resistance to adaptation, and reduced noise correlations
(rather than just with elevated firing rates), and (1b) that cholinergic Ipc serves as a multiplexed mechanism for
regulating these diverse OTid coding features. Second, we aim to elucidate a neuromodulatory mechanism for
the control of categorization. Our hypotheses (based on our model predictions) are (2a) that (hitherto
uncharacterized) spatially-specific cholinergic input onto Imc neurons causes multiplicative modulation of Imc
activity, and (2b) that it serves as a mechanism to enhance the degree of categorical signaling of the most salient
stimulus by OTid. Third, we aim to uncover the source and broader functional logic of this cholinergic input. Our
hypotheses are (3a) that Ipc is the dominant source of cholinergic input onto Imc neurons, and (3b) that in
parallel, Ipc, which influences activity across the layers of the OT, selectively spares the OT layer that provides
input to it (layer 10); revealing a precisely organized circuit design that minimizes runaway feedback excitation
in this network. We will test these hypotheses using in vivo electrophysiology and drug iontophoresis during
visual stimulus presentation in awake, head-fixed barn owls, together with computational modeling. Preliminary
data from the three aims support our hypotheses. Results from the proposed wor...

## Key facts

- **NIH application ID:** 10850784
- **Project number:** 5R01EY027718-08
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Shreesh P Mysore
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $457,561
- **Award type:** 5
- **Project period:** 2017-03-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10850784

## Citation

> US National Institutes of Health, RePORTER application 10850784, Stimulus competition and visuospatial selection: Neural circuit and computational mechanisms (5R01EY027718-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10850784. Licensed CC0.

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