# Using new methods for voltage imaging to assay the engagement of specific cell-types and brain rhythms in prefrontal-dependent cognition.

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $403,750

## Abstract

PROJECT SUMMARY
Cognitive deficits represent the major cause of disability in schizophrenia but are refractory to all existing
treatments. EEG oscillations in the gamma-frequency range are recruited by many cognitive tasks, and task-
evoked gamma oscillations are deficient in schizophrenia. Furthermore, gamma oscillations are generated by
parvalbumin interneurons, which are abnormal in schizophrenia. This suggests that gamma oscillations may be
biomarkers for cognitive deficits and parvalbumin interneuron dysfunction in schizophrenia. In fact, many
studies suggest that gamma oscillations may actively contribute to cortical circuit functions that are necessary
for cognition. Indeed, our previous work has shown that optogenetically restoring interneuron-generated
gamma oscillations in the prefrontal cortex can rescue cognitive deficits in mutant mice. However, there are
many ways to measure gamma oscillations – some of these capture the strength of gamma oscillations at a
single site whereas others reflect synchronization across sites. Our recent work suggests that long-range
synchronization of gamma-frequency activity in PV interneurons, rather than just gamma-frequency activity at a
single site, may be required for prefrontal cortex-dependent cognitive flexibility. Furthermore, we have
developed new ways of measuring signals from genetically encoded voltage indicators in order to measure
gamma-frequency synchronization between specific cell-types at different locations. We will now leverage
these advances to: (1) use our novel analyses and GEVIs to directly measure cell-type specific gamma-
frequency synchronization in behaving rodents; (2) determine which particular ways of quantifying EEG
gamma oscillations best capture this synchronization; (3) evaluate how well these EEG measures correlate
with changes in PV interneuron synchronization and behavioral performance elicited by several
pharmacological manipulations including some which are known to rescue deficits in gamma oscillations and
prefrontal-dependent cognition in mutant mice, and (4) validate, via optogenetics, that these EEG measures
are sensitive and specific indicators for changes in PV interneuron function. This project will define particular
EEG measures that reflect cell-type specific patterns of long-range synchronization underlying specific aspects
of cognition.

## Key facts

- **NIH application ID:** 10210219
- **Project number:** 5R01MH121342-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Vikaas Singh Sohal
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $403,750
- **Award type:** 5
- **Project period:** 2019-09-05 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10210219

## Citation

> US National Institutes of Health, RePORTER application 10210219, Using new methods for voltage imaging to assay the engagement of specific cell-types and brain rhythms in prefrontal-dependent cognition. (5R01MH121342-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10210219. Licensed CC0.

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