Analysis of sensory dendrite morphology and its impact on olfactory sensitivity - PROJECT SUMMARY
This project aims to describe the precise dendritic morphology of identified olfactory receptor neurons (ORNs)
with volume electron microscopy (EM) and to investigate the structure-function relationship between dendritic
morphology and olfactory sensitivity. In the nervous system, information is received by specialized neuronal
processes termed dendrites, whose characteristic arborization patterns are typically associated with specific
functions of neuronal subtypes. For example, the arborizations of somatosensory neurons define the geometry
and size of their receptive fields. In contrast, the numerous cilia or dendritic branches of olfactory receptor
neurons (ORNs) are thought to increase sensory surface area for heightened sensitivity. However, the functional
impacts of dendritic size and shape on olfaction have yet to be experimentally defined. Understanding this
structure-function relationship has been particularly hindered by the lack of morphological and morphometric
information from identified ORNs. To bridge this knowledge gap, the proposed research leverages the powerful
genetic toolkit and tractable olfactory system of D. melanogaster. The dendrites of fly ORNs are encapsulated
in sensory hairs, named sensilla, which fall into four morphological classes: basiconic, coeloconic, intermediate
and trichoid. To precisely define ORN dendritic morphologies, we have pioneered technical breakthroughs which
allowed us to perform serial block-face scanning electron microscopy (SBEM) with cryofixed, genetically labeled
antennal tissues. 3D reconstructions of identified neurons reveal remarkable morphological diversity among
ORNs housed in different sensillum classes. The dendrites of basiconic and intermediate ORNs display multiple
branches, whereas those of coeloconic and trichoid neurons are typically unbranched. And although neurons
expressing the same receptor are expected to exhibit similar arborization geometry, we found subsets of
homotypic basiconic ORNs which instead show diverse branching patterns and varied sensory surface area. Is
dendritic arborization diverse for certain ORN subtypes? If so, does this morphological heterogeneity give rise
to variable sensitivity among homotypic ORNs in these neuronal populations? Moreover, is odor detection
affected by the branching diversity and surface-area disparity of different ORN types? This proposal will address
these fundamental questions by evaluating the dendritic heterogeneity of identified ORNs (Aim 1), and by
determining the functional impact of dendritic size and shape on olfactory sensitivity (Aim 2). A multidisciplinary
approach—employing SBEM, molecular genetics, and single-sensillum recording—will be employed. Successful
execution of this proposal is expected to yield critical insights into whether and how dendritic size and shape
impact olfactory function. Importantly, a large morphological and morphometric dataset for identified ORNs’
sensory dendrites will be generated and made available to the neuroscience community. This rich information
will facilitate comparative morphometric analyses and computational modeling, and also pave the way for future
studies to determine the molecular mechanisms underlying diverse ORN dendritic morphologies.