# BLRD Research Career Scientist Award Application

> **NIH VA IK6** · VA BOSTON HEALTH CARE SYSTEM · 2021 · —

## Abstract

Sleep loss and sleep disorders (e.g., sleep apnea) lead to excessive daytime sleepiness and impaired
attention & cognition. The symptoms of sleep disturbance are now recognized as major contributors to
accident rates and decreased workplace productivity. Attention, concentration, and cognitive problems are also
a major feature of other disorders that are prevalent in US veterans – e.g., TBI, PTSD, Alzheimer's disease,
depression, substance use disorder, and schizophrenia. Understanding the brain circuitry controlling attention
will guide the development of treatments to ameliorate cognitive impairments of these conditions. Abundant
evidence indicates that the basal forebrain (BF) region contains cortically projecting & wakefulness promoting
neurons that are important for cortical activation, behavioral arousal/alertness, and attention. Although previous
work has focused on the role of BF cholinergic neurons in attention, advances in optogenetic methods allow
the investigation of BF parvalbumin (PV) containing GABAergic neurons.
 Work on my current Merit grant indicates that selective excitation of BF PV neurons in mice produces
cortical activation, wakefulness, and behavioral arousal. Our new data show that excitation of BF PV neurons
enhances vigilant attention to rescue reaction time deficits produced by sleep loss and also enhances
attention-dependent associative learning without affecting motivation (i.e. hunger, a potential side effect) or
reward (i.e. abuse potential). Our overarching hypothesis to explain these findings is that BF PV neurons
mediate rapid changes in alertness/attention by quickly activating the cortex in anticipation of, or in response
to, meaningful or surprising sensory stimuli. Research methods used to evaluate this hypothesis include i) fiber
photometry to measure the activity of BF PV neurons, and, ii) optogenetic methods to either excite or inhibit
these neurons in mice; both approaches are combined with behavioral tests and measures of cortical electrical
activity. The translational relevance of this basic science project is that BF PV excitation may be used to
enhance cognition with limited side effects and low abuse potential.
 The overarching goal of this research program is to understand the mechanisms of basal forebrain
regulation of cortical activity and cognition which could lead to treatments for a variety of disorders that impact
US Veterans. For example, the pro-cognitive properties of the BF PV model described above can be readily
applied to additional mouse models of diseases that are prevalent in the US Veteran population including
Alzheimer’s disease (AD) and traumatic brain injury (TBI). Indeed, other ongoing studies with research
fellow (Dr. Felipe Schiffino) and collaborators (Drs. Jay McNally & Lee Goldstein) are testing BF PV excitation
benefits in mouse models of AD and TBI.
1

## Key facts

- **NIH application ID:** 10236079
- **Project number:** 1IK6BX005714-01
- **Recipient organization:** VA BOSTON HEALTH CARE SYSTEM
- **Principal Investigator:** ROBERT E STRECKER
- **Activity code:** IK6 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2021-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10236079

## Citation

> US National Institutes of Health, RePORTER application 10236079, BLRD Research Career Scientist Award Application (1IK6BX005714-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10236079. Licensed CC0.

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