# Optical Dissection of the Neural Circuitry Controlling Sensorimotor Gating

> **NIH NIH K01** · NORTHWESTERN UNIVERSITY · 2020 · $137,347

## Abstract

Project Summary/Abstract
CANDIDATE/ENVIRONMENT: Dr. Jones Parker is a research associate in the Department of Biology at Stanford
University. Having recently completed a postdoctoral fellowship with Dr. Michael Ehlers at Pfizer, Dr. Parker seeks to
expand upon his expertise using calcium imaging in freely behaving mice to study neuropsychiatric disorders in Dr. Mark
Schnitzer's laboratory, where the technique was pioneered. CAREER DEVELOPMENT: This award will ensure that Dr.
Parker finalizes his training in the acquisition and analysis of large-scale calcium imaging datasets and will facilitate his
transition into a new field of research. More specifically, it affords Dr. Parker the time to refine his programming and
analysis skills and provides him exposure to basic research in psychiatric diseases. Ultimately, this award will position Dr.
Parker to draw upon cutting-edge techniques to execute more developed programs in his future independent research
group. RESEARCH STRATEGY: The fact that individual mental illnesses can result from a host of diverse genetic and
environmental risk factors has made it exceedingly difficult to therapeutically target their underlying causes. One
explanation for this `many pathways to one disease' relationship is that the brain region responsible for a given set of
symptoms can become disrupted by distinct connections from multiple other brain regions. Thus a better understanding
disease-related neural circuitry might explain the many ways the circuitry can be disrupted to yield the same set of
symptoms. To address this idea, we will use a viral-genetic approach to optogenetically manipulate or image calcium
activity in distinct neuronal populations that project to the brain nucleus that controls sensorimotor gating. Deficits in
sensorimotor gating occur in a wide range of diverse neuropsychiatric disorders, suggesting that there are multiple ways
for the circuitry controlling the behavior to become disrupted. Sensorimotor gating is readily assessed in rodents by
measuring pre-pulse inhibiton (PPI), which tests the ability of a weak, auditory pre-stimulus to attenuate an animal's
acoustic startle response (ASR). The basic neural circuit controlling the ASR is well characterized: the caudal pontine
nucleus (PnC) modulates the amplitude of the startle response based on auditory information from the cochlear nucleus.
To determine how and which brain regions modulate the ASR and PPI, we will use a retrogradely transported Cre-
recombinase expressing virus (CAV2-Cre) to selectively express the genetically encoded calcium sensor (GCaMP6) or
excitatory/inhibitory opsins (ChR2/NpHR) in neurons that directly project to the PnC. We will then use miniature
fluorescence microscopes to image calcium activity in PnC-projecting neurons during acoustic startle and PPI. To
establish a causal role for the dynamics we observe in PnC-projecting neurons during PPI, we will also optogenetically
manipulate these neurons during acoustic s...

## Key facts

- **NIH application ID:** 9895866
- **Project number:** 5K01MH113132-04
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Jones G Parker
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $137,347
- **Award type:** 5
- **Project period:** 2019-01-24 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9895866

## Citation

> US National Institutes of Health, RePORTER application 9895866, Optical Dissection of the Neural Circuitry Controlling Sensorimotor Gating (5K01MH113132-04). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9895866. Licensed CC0.

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