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Principal Investigator: Dominic David Frank
Organization: ROCKEFELLER UNIVERSITY
Fiscal Year: 2024
Award: $125,902
Funding agency: National Institute on Deafness and Other Communication Disorders
Project Summary
Impaired social communication is a major feature of common neurodevelopmental disorders like autism
spectrum disorder. Nevertheless, cellular mechanisms underlying the development of affected brain networks
remain uncertain, despite the potential to inspire novel diagnostics and pharmacological interventions. Hence,
this represents a key area of need in modern biomedical research. This career development proposal utilizes
an emerging invertebrate model organism, the clonal raider ant, to investigate cellular mechanisms of
neurodevelopment in olfactory brain circuits uniquely adapted for communication.
Ants have evolved a remarkable capacity for chemical communication. Information is encoded by large arrays
of pheromones exuded by dedicated exocrine glands and is received and processed by highly advanced
olfactory systems. With approximately 500 olfactory glomeruli, the clonal raider ant antennal lobe (AL) is more
complex than any other known insect and is evocative of the olfactory bulb in the brain of mammals
(Drosophila have only ~50 AL glomeruli, for reference). Previous work in our lab suggests the evolution of
sociality in ants may have coincided with unique neurodevelopmental logic in the AL supportive of this
complexity. Over three aims, this project investigates early neuronal activity in pupal ant olfactory sensory
neurons (OSNs) and its significance for the normal wiring of brain circuits in adults. First, Aim 1 utilizes
GCaMP-expressing transgenic ants and in vivo two-photon microscopy to characterize spontaneous neuronal
activity in the OSNs of clonal raider ant pupae. In Aim 2, OSN activity is manipulated throughout development
using novel transgenic ant lines and the impact of these perturbations on olfactory circuit structure is
investigated. In Aim 3, optogenetic tools are used to disrupt OSN activity during an isolated period of
widespread synaptogenesis in mature ant pupae and the effect on neuropil volume is examined.
Terms: <2-photon><2-photon microscopy><21+ years old><ADP-ATP Translocase-1><ADP/ATP Carrier 1><ADP/ATP Translocator of Skeletal Muscle><ANT gene><ANT protein><ANT1><ASD><Address><Adenine Nucleotide Translocator 1><Adult><Adult Human><Affect><Anatomic Sites><Anatomic structures><Anatomy><Animals><Ants><Area><Autism><Autistic Disorder><Behavioral><Biomedical Research><Brain><Brain Nervous System><Brain region><Calcium><Calcium Ion Signaling><Calcium Oscillations><Calcium Signaling><Calcium Waves><Chemicals><Cognitive><Communication><Complex><Data><Dedications><Development><Diagnosis><Distant><Drosophila><Drosophila genus><Drosophila melanogaster><Dysfunction><Early Infantile Autism><Encephalon><Evolution><Exocrine Glands><Flies><Fluorescence Light Microscopy><Fluorescence Microscopy><Functional disorder><Genetic><Human><Image><Immunohistochemistry><Immunohistochemistry Cell/Tissue><Immunohistochemistry Staining Method><Infantile Autism><Insecta><Insects><Insects Invertebrates><Intervention><Intervention Strategies><Invertebrata><Invertebrates><K channel><Kanner's Syndrome><Lobe><Logic><Mammalia><Mammals><Membrane><Modeling><Modern Man><Modernization><Molecular><Nerve Cells><Nerve Unit><Nervous System><Neural Cell><Neural Development><Neurobiology><Neurocyte><Neurodevelopmental Disorder><Neurologic Body System><Neurologic Organ System><Neurological Development Disorder><Neurons><Neuropil><Neurosciences Research><Olfactory Pathways><Olfactory system><Pathogenesis><Phenotype><Pheromone><Physiopathology><Potassium Channel><Potassium Ion Channels><Process><Public Health><Pupa><Research><SLC25A4><SLC25A4 gene><Societies><Solute Carrier Family 25(Mitochondrial Carrier; Adenine Nucleotide Translocator), Member 4><Structure><Testing><Time><Transgenic Organisms><Work><adulthood><autism spectral disorder><autism spectrum disorder><autistic spectrum disorder><axon growth cone guidance><axon guidance><career development><developmental><early adulthood><emerging adult><experiment><experimental research><experimental study><experiments><fly><fruit fly><imaging><in vivo><interventional strategy><lobes><membrane structure><model organism><mutant><nervous system development><neurobiological><neurodevelopment><neurodevelopmental disease><neurogenetics><neuronal><new diagnostics><next generation diagnostics><novel><novel diagnostics><olfactory bulb><olfactory bulb glomeruli><olfactory bulb glomerulus><olfactory circuitry><olfactory circuits><olfactory glomeruli><olfactory glomerulus><olfactory sensory neurons><optogenetics><overexpress><overexpression><pathophysiology><pharmacologic><sensory system><social><social cognition><social communication impairment><social model><synapse formation><synaptogenesis><tool><transgenic><two photon excitation microscopy><two photon microscopy><two-photon>