# Piriform cortex: sequential developmental events

> **NIH NIH R01** · YALE UNIVERSITY · 2024 · $418,750

## Abstract

Project Summary – Abstract
 The perception of odors begins in the olfactory epithelium when odorant ligands bind to molecular
receptors expressed on the cilia of the olfactory sensory neurons, each of which expresses only 1 of ~1200
candidate receptors. As the sensory neuron axons exit the epithelium they progress over the surface of
the olfactory bulb and all of the axons coming from neurons expressing the same odorant receptor
converge into only 2/3 glomeruli/olfactory bulb. However, the convergence and discrete circuitry of the
olfactory bulb is not apparent in piriform cortex (PCX), at least grossly. Afferent projections to piriform
appear divergent and broadly distributed. Moreover, in contrast to the more widely studied neocortex, the
3-layer piriform paleocortex does not exhibit a definitive columnar structure, leaving open the question of
whether principles learned from neocortex can be applied to understanding piriform. Most of what we
know of the neuronal and synaptic organization of piriform has come from early studies of rat and opossum,
that while important did not benefit from contemporary genetic and molecular tools. The mouse, which
has emerged as the dominant mammalian model for studies of the olfactory epithelium and bulb, has
benefited immeasurably from these new tools. However, there are few examples of the application of
contemporary genetic and molecular methods to studies of mouse piriform cortex. We remain woefully
ignorant of the most fundamental features of mouse piriform cortex When do synapses first appear in
mouse PCX and when do they achieve laminar segregation? What is the organization of the ipsi- and
contralateral association axons that likely contribute to the cortical coding of odors in ensembles of
neurons? What are the molecular mechanisms/transcription factors underlying the fate and specificity of
PCX neurons/structure? To begin addressing these significant gaps in our knowledge we are proposing 3
specific aims: Aim 1 addresses the emergence of synaptic circuits in PCX and tests the hypothesis that
it occurs in a spatio-temporal format that distinguishes the laminar specificity of circuits. Aim 2 addresses
the PCX associational connectome, both ipsilateral and contralateral via the anterior commissure. Aim 3
tests the spatiotemporal expression of transcription factors (TFs) that we hypothesize are important in
establishing PCX pyramidal neuron identity and contributions to the association axon network in PCX.
Selective TFs will be knocked out using CRISPR to determine their role at a more granular level.
Collectively these innovative studies will provide new insight into the mechanisms regulating the
organization of PCX and the foundations of odor coding in PCX.

## Key facts

- **NIH application ID:** 10815569
- **Project number:** 5R01DC013791-08
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Charles A Greer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $418,750
- **Award type:** 5
- **Project period:** 2014-12-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10815569

## Citation

> US National Institutes of Health, RePORTER application 10815569, Piriform cortex: sequential developmental events (5R01DC013791-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10815569. Licensed CC0.

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