# Supplement to Basal Forebrain Modulation of Olfactory Bulb Function

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2022 · $347,592

## Abstract

Abstract As we age, the risk for neurodegenerative disorders such as Alzheimer's disease (AD) and related
neurodegenerative disorders (NDD) increases dramatically. AD afflicts tens of millions in the U.S. and this
number is expected to increase as a proportion of the population over the coming decades. Sadly, our under-
standing of the neurobiology of aging, AD and other NDDs is limited, and effective therapeutic interventions are
meager. One of the devastating symptoms of AD is a disruption of emotional recognition and interpersonal
social behaviors. Additionally, a hallmark shared by multiple NDDs and aging is an early manifestation of
olfactory dysfunction. This suggests the olfactory system may be uniquely sensitive to the cascade of changes
underlying altered brain function in NDDs and aging. We hypothesize in AD and the normal aging OB, that there
is a dysregulation in the basal forebrain to olfactory bulb excitation/inhibition (E/I) balance. These inputs are, in
part, regulated by endocannabinoids (EC). ECs are signaling molecules that modulate synaptic transmission
throughout the brain. In this supplement, we will test the role of ECs in a mouse model of AD, the 5xFAD line of
animals which recapitulates many of the neuropathology phenotypes associated with familial AD. This approach
will employ a novel ‘all optical’ combination of fiber photometry with in vivo EC agonist uncaging to directly
measure EC regulated glutamate and GABA release from the basal forebrain onto olfactory interneurons.
Relevance to AD research: The perturbation of sensory information in the progression of AD is poorly
understood. Data indicates that early symptoms of many neurodegenerative disorders involve olfactory
dysfunction, which as well as being an early hallmark of the disorders has significant standard of living impact.
Olfactory function is linked to depression and other psychiatric disorders including nutrition, since the majority
of the perception of flavor is a function of olfaction and not ‘taste’ per se. The absence of complex flavor
information heightens risk of depression and poor nutrition. Understanding how olfactory circuits function in
AD may open avenues of therapeutics to mitigate symptoms of socio-sensory dysfunction to improve patient
quality of life. This supplement is intended to take our parent grant study of basal forebrain modulation into an
animal model that recapitulates elements of AD neuropathology to begin to explore how basal forebrain
regulation of olfactory circuits may be influenced by aging and progressive dysfunction in AD.

## Key facts

- **NIH application ID:** 10492157
- **Project number:** 3R01DC010915-09S1
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** ADAM C PUCHE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $347,592
- **Award type:** 3
- **Project period:** 2011-02-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10492157

## Citation

> US National Institutes of Health, RePORTER application 10492157, Supplement to Basal Forebrain Modulation of Olfactory Bulb Function (3R01DC010915-09S1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10492157. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*