# Olfactory Bulb Local Circuits

> **NIH NIH R01** · YALE UNIVERSITY · 2021 · $355,938

## Abstract

Project Summary – Abstract
 The perception of odors begins in the olfactory epithelium when odorant ligands bind on olfactory
sensory neurons, each of which expresses only 1 of ~1200 candidate receptors. Axons coming from
neurons expressing the same odorant receptor converge into only 2/3 glomeruli/olfactory bulb where
they synapse onto projection neurons, each of which innervates a single glomerulus. Deep to the
glomeruli, within the external plexiform layer (EPL), odor coding is tuned by local synaptic circuits.
Deciphering connectivity with the EPL is the first step toward understanding the mechanisms of central
odor processing. Several hypotheses of local processing within the EPL have been proposed and its
synaptic organization is often presented as canonical. However, we lack a fundamental understanding of
the how the diversity in interneuron, granule cell (GC), structural, molecular, and topographical
organization affects EPL local circuits, which is an impediment to interpreting functional studies. Here we
propose a series of testable hypotheses and experiments on factors that may influence the organization
of GCs and their local synaptic circuits. These studies build on our prior developmental and
ultrastructural work as well as a systematic review of the current literature and the recognition that
fundamental features of EPL organization and connectivity have been presumed, but not empirically
tested. First, we propose to address the hypotheses that the clonal history, timing and order of GC
neurogenesis are determinants of their organization/distribution in the olfactory bulb. Using multiple
strategies to track neurogenesis, cell lineage/fate we will assess the spiny dendritic arbors of GCs
beginning in the embryo and continuing at regular intervals to those generated up 200 days of age. In
addition, and not among prior studies, we propose to carefully assess the organization of the GC basal
dendrites which are the primary recipients of incoming centrifugal modulation (Rothermei and
Wachowiak, 2014; Kapoor et al., 2016; de Almeida et al., 2015). Second, we propose to test the
hypothesis that the synaptology and molecular features of the dendrodendritic synapses in the EPL vary
as a function of age. Presently, little is known of the structural features that regulate dendrodendritic
synapses or how the molecular properties of the mitral to GC and the reciprocal GC to mitral cell
synapses may differ. The analyses will address that fundamental problem and provide a sound
foundation for the interpretation of functional analyses of odor processing. In addition, we will address
the spatial distribution of synaptic appositions along 2o dendrites and the degree to which the features of
the synaptic specialization change with age. Because the questions we propose to address are
important throughout the nervous system, we anticipate that the results will have broad implications for
understanding targeting, laminar specificity, and synaptic connec...

## Key facts

- **NIH application ID:** 10130377
- **Project number:** 5R01DC016851-03
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Charles A Greer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $355,938
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10130377

## Citation

> US National Institutes of Health, RePORTER application 10130377, Olfactory Bulb Local Circuits (5R01DC016851-03). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10130377. Licensed CC0.

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