# Role of the basal forebrain in sleep loss induced attention impairments

> **NIH VA I01** · VA BOSTON HEALTH CARE SYSTEM · 2022 · —

## 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 the attention and 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
our current Merit grant indicates that selective excitation of BF PV neurons in mice produces cortical activation,
wakefulness, and behavioral arousal. Our new preliminary data suggest that excitation of BF PV neurons can
enhance attention, cognition, and rescue reaction time performance impairments produced by sleep loss.
 The findings described led us to two testable hypotheses: 1) BF PV neurons mediate rapid changes in
alertness/attention by quickly activating the cortex in response to meaningful or surprising sensory stimuli.
2) Excitation of BF PV neurons does not alter motivation (e.g., hunger) and is not rewarding indicating these
neurons can enhance attention and cognition with limited side effects and low addictive potential. Our model
prediction: In response to meaningful or surprising sensory stimuli, BF PV neurons briefly activate the cortex,
enhancing cortical processing and alertness which facilitates attention-dependent reaction time performance
and associative learning. The work will address a gap in our knowledge by demonstrating that regulation of
cortical activation by BF PV neurons is important for the control of attention. Methods used include fiber
photometry to measure the activity of BF PV neurons and optogenetics to excite and inhibit these neurons in
mice; both will be combined with behavioral tests and measures of cortical electrical activity. The 3 aims are:
 Aim 1 will demonstrate that increasing and decreasing the activity of BF PV neurons can modulate cortical
responses to repetitive presentations of sensory stimuli. This finding will provide a plausible mechanism for
how these neurons enhance the attention dependent behavioral performance studied in Aims 2 & 3.
 Aim 2 will demonstrate that BF PV excitation enhances sustained attention and performance in a mouse
reaction time test like the test used in humans to detect sleepiness and sustained attention deficits.
Exp...

## Key facts

- **NIH application ID:** 10359072
- **Project number:** 5I01BX002774-06
- **Recipient organization:** VA BOSTON HEALTH CARE SYSTEM
- **Principal Investigator:** ROBERT E STRECKER
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2015-10-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10359072

## Citation

> US National Institutes of Health, RePORTER application 10359072, Role of the basal forebrain in sleep loss induced attention impairments (5I01BX002774-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10359072. Licensed CC0.

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