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Principal Investigator: Hala Galal El-Nahal
Organization: DUKE UNIVERSITY
Fiscal Year: 2024
Award: $41,436
Funding agency: National Institute of Mental Health
PROJECT SUMMARY
The claustrum is a narrow, subcortical sheet of gray matter with interconnections across the cerebral cortex. Its
irregular shape and deep location make it difficult to study with classical neurophysiological techniques. Recent
genetic technologies such as optogenetics provide new hope for understanding the claustrum. They have
advanced its study in rodents, implicating the claustrum in an array of sensorimotor and cognitive functions.
Circuit-specific studies are needed to resolve how these functions map to the claustrum’s widespread
connections. Such studies would be especially valuable in macaque monkeys, the animal model most
homologous to humans. My overall goal is to translate viral technologies to monkeys and use them to study the
role of a specific claustrum-prefrontal cortical circuit in visuo-saccadic behavior. During systematic testing of viral
vectors in macaques, I identified a promising candidate for delivering opsin genes to the claustrum: the
retrograde virus rAAV2-retro. When injected into the frontal eye field (FEF), a prefrontal cortical area involved in
vision, movement, and cognition, rAAV2-retro constructs yielded strong labeling of FEF-projecting claustrum
neurons. This finding provides a long-sought, unique opportunity to study claustrum neurons with circuit-level
specificity in the primate brain. I propose to validate viral techniques in the claustro-FEF circuit and use them to
test my overall hypothesis that the claustrum mediates competitive selection of the most behaviorally relevant
stimulus via suppression of all other stimuli. To test my hypothesis, I have three integrated aims. In Aim 1, I will
conduct anatomical tracing studies to elucidate the motif of connectivity between the claustrum and FEF. In Aim
2, I will use rAAV2-retro to express an inhibitory opsin in FEF-projecting claustrum neurons. Then I will use
phototagging to identify those neurons and extracellularly record from them to characterize the signals sent from
the claustrum to the FEF during a battery of saccade tasks. In Aim 3, I will use the same inhibitory opsins to
selectively silence FEF-projecting claustrum neurons, allowing me to determine whether they are required for
competitive selection of saccade targets. The claustrum is implicated in a wide range of neurological diseases
and neuropsychiatric disorders. Thus, the results of the proposed work will help reveal how pathological changes
to neural activity in the claustrum may contribute to brain disorders. In addition to its clinical relevance, the
proposed work will significantly expand my doctoral training to include neural recording and optogenetic methods
in non-human primates.
Terms: <Address><Animal Model><Animal Models and Related Studies><Animals><Appearance><Area><Attention><Back><Behavior><Behavioral><Brain><Brain Diseases><Brain Disorders><Brain Nervous System><Cell Body><Cell Communication and Signaling><Cell Signaling><Cells><Cerebral cortex><Claustral structure><Claustrum><Cognition><Common Rat Strains><Disease><Disorder><Dorsum><Encephalon><Encephalon Diseases><Esthesia><Esthetics><Exhibits><Eye Movements><Functional MRI><Functional Magnetic Resonance Imaging><Genes><Genetic Technics><Genetic Techniques><Geometry><Goals><Health><Histology><Human><Injections><Intracellular Communication and Signaling><Intracranial CNS Disorders><Intracranial Central Nervous System Disorders><Jaw><Label><Leanness><Location><Macaca><Macaque><Maps><Mediating><Methods><Modern Man><Monkeys><Motor><Movement><Nerve Cells><Nerve Unit><Nervous System Diseases><Nervous System Disorder><Neural Cell><Neurocyte><Neurologic Disorders><Neurological Disorders><Neurons><Operative Procedures><Operative Surgical Procedures><Opsin><Optics><Outcome><Pain><Painful><Pathologic><Performance><Physiologic><Physiological><Prefrontal Cortex><Primates><Primates Mammals><Proteins><Psychophysics><Publishing><Rat><Rats Mammals><Rattus><Recombinant adeno-associated virus><Recombinant adeno-associated virus (rAAV)><Research Design><Rod-Opsin><Rodent><Rodentia><Rodents Mammals><Role><Saccades><Saccadic Eye Movements><Saccadic Pursuit><Sensation><Sensorimotor functions><Shapes><Sight><Signal Transduction><Signal Transduction Systems><Signaling><Sleep><Specificity><Stimulus><Structure><Study Type><Surgical><Surgical Interventions><Surgical Procedure><System><Techniques><Technology><Testing><Thinness><Training><Translating><Viral><Viral Vector><Virus><Vision><Visual><Work><anatomical tracing><biological signal transduction><body movement><career><clinical relevance><clinically relevant><cognitive function><decrease resilience><decrease resiliency><distraction><experiment><experimental research><experimental study><experiments><extracellular><fMRI><fluorophore><frontal eye fields><genetic approach><genetic strategy><genetic technology><gray matter><lower resilience><lower resiliency><model of animal><neural><neurological disease><neuronal><neurophysiological><neurophysiology><neuropsychiatric disease><neuropsychiatric disorder><new approaches><non-human primate><nonhuman primate><novel approaches><novel strategies><novel strategy><optical><optogenetics><psychophysical><rAAV><recombinant AAV><social role><study design><substantia grisea><surgery><viral testing><virus testing><visual cognition><visual function><visual motor><visuomotor>