# Investigating the effects of olfactory critical period odorant exposure on the trace amine-associated receptor4 olfactory circuit

> **NIH NIH F31** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $48,974

## Abstract

Project Summary
Innate behavioral responses to emotionally salient cues in the environment are thought to be set in the brain
through hardwired circuits. In mice, the olfactory detection and processing pathways are well characterized,
with olfactory sensory neurons (OSNs) that express the same one odorant receptor (OR) coalescing to form
two glomeruli per olfactory bulb (OB). Mitral cells and tufted cells (M/TCs) send a single apical dendrite into
these glomeruli to receive input, and project their axons to various downstream brain regions. This highly
organized glomerular map is maintained throughout the mouse’s life. However, the olfactory bulb has a
developmental critical period from postnatal days 0 to 14 (P0 – P14), during which enrichment with a neutral
odorant produces lasting changes: both the volume of the glomeruli and responsiveness of M/TCs to the
enriched odorant increase. However, less is known about how critical period exposure to odorants with innate
valence alters OB circuits. A recent study has shown that exposure to the innately aversive odorant
phenethylamine (PEA) during the olfactory critical period produces behavioral changes and alters axon
projection patterns of OSNs expressing the trace-amine associated receptor class 4 (TAAR4 or T4). Mice
exposed to PEA during the critical period no longer show innate aversion to PEA in adulthood; furthermore,
these mice have on average five T4 glomeruli per hemisphere rather than the typical two. Currently, this is the
only report of changes in the OB circuitry and behaviors following exposure to an innately aversive odorant
during the olfactory critical period. What remains unknown is how either the OSNs or the M/TCs within the T4
glomerular module change in their PEA responsiveness following critical period PEA exposure. Additionally,
whether these behavioral and structural changes persist following complete OSN ablation and reinnervation of
the OB has yet to be investigated. To fill this gap in knowledge, I propose experiments to test the critical period
exposure to the aversive odorant PEA alters OB circuitry response patterns to produce persistent behavioral
and structural changes to elicit attraction to PEA. In Aim 1, I will first use 2-photon calcium imaging to identify
changes in OSN and MC/TC odor responses within the T4 glomerular module following critical period PEA
exposure. I will then determine whether critical period PEA exposure changes the intrinsic excitability of M/T
cells using whole cell voltage clamp electrophysiology in OB slices. In Aim 2, I will determine whether the
behavioral and glomerular organization changes elicited by critical period PEA exposure persist after OSN
ablation via methimazole (MMZ) treatment and subsequent reinnervation of the OB, using chronic in vivo
structural 2-photon imaging of T4 glomeruli and repeated odor preference testing in saline vs. MMZ treated
mice. These data will advance our understanding of the effects of critical period exp...

## Key facts

- **NIH application ID:** 10860966
- **Project number:** 5F31DC021353-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Jordan Duran Gregory
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 5
- **Project period:** 2023-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10860966

## Citation

> US National Institutes of Health, RePORTER application 10860966, Investigating the effects of olfactory critical period odorant exposure on the trace amine-associated receptor4 olfactory circuit (5F31DC021353-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10860966. Licensed CC0.

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