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Principal Investigator: Gregory Patrick Davis
Organization: WEILL MEDICAL COLL OF CORNELL UNIV
Fiscal Year: 2024
Award: $79,284
Funding agency: National Institute of Mental Health
PROJECT SUMMARY / ABSTRACT
Persistent activity in neural circuits supports a variety of brain functions from motor control to navigation to
perceptual decision-making. Correlational studies show significant variation in persistent activity patterns during
different behaviors, suggesting that individual circuits perform flexible computations that depend on the context
of ongoing brain activity and motor functioning. However, establishing the causal significance of this variability
is difficult due to technical limitations in existing tools for precisely manipulating circuit dynamics. A tractable
system for overcoming this challenge is the zebrafish, a vertebrate model organism with an optically accessible
brain that allows simultaneous calcium imaging and optogenetic stimulation with laser microscopy. Research in
our lab focuses on the zebrafish oculomotor integrator, a hindbrain circuit involved in adaptive control of gaze
position. This circuit generates persistent activity that directly drives easily quantified motor behavior. In prior
work, our lab found that different patterns of integrator activity are associated with distinct types of eye
movements, but it is unclear how these context-dependent dynamics contribute to oculomotor control and how
they relate to the development of sophisticated behavior. In the proposed research, I will conduct simultaneous
two-photon imaging and optogenetic stimulation during visuomotor behavior to determine how different patterns
of integrator dynamics contribute to different types of eye movements. First, I will collect a comprehensive
longitudinal dataset of brain-wide neural activity in the larval and juvenile zebrafish during a broad range of
oculomotor behaviors, testing if indeed the number of persistent patterns in the integrator expands with the
behavioral repertoire. Then, I will perform real-time closed-loop stimulation of the integrator network at single-
cell resolution, steering circuit dynamics along specific patterns of activity to test their causal impact on motor
outputs. This research will improve our understanding of flexible control by memory circuits and establish new
paradigms for precise manipulation of network dynamics.
Terms: <2-photon><Adolescent><Adolescent Youth><BRAIN initiative><Behavior><Behavioral><Biologic Models><Biological Models><Brachydanio rerio><Brain><Brain Nervous System><Brain Research through Advancing Innovative Neurotechnologies initiative><Calcium><Cell Body><Cells><Cognitive><Correlation Studies><Danio rerio><Data Set><Decision Making><Development><Disease><Disorder><Electrophysiology><Electrophysiology (science)><Encephalon><Eye><Eye Movements><Eyeball><Fishes><Fixation><Goals><Health><Hind Brain><Image><Immediate Memory><Individual><Lab Findings><Laboratory Finding><Laser Microscopy><Link><Memory><Methods><Modality><Model System><Motor><Motor Cell><Motor Neurons><Motor output><Nerve Cells><Nerve Unit><Neural Cell><Neurocyte><Neurons><Neurophysiology / Electrophysiology><Optics><Output><Pattern><Phase><Photic Stimulation><Population><Position><Positioning Attribute><R-Series Research Projects><R01 Mechanism><R01 Program><Research><Research Grants><Research Project Grants><Research Projects><Research Resources><Resolution><Resources><Rhombencephalon><Role><Short-Term Memory><Shortterm Memory><Statistical Correlation><Statistical Data Analyses><Statistical Data Analysis><Statistical Data Interpretation><System><Techniques><Testing><Therapeutic><Time><Variant><Variation><Vertebrate Animals><Vertebrates><Visual><Visual Stimulation><Work><Zebra Danio><Zebra Fish><Zebrafish><brain control><developmental><electrophysiological><eye velocity><flexibility><flexible><gaze><hindbrain><imaging><improved><information processing><insight><juvenile><juvenile human><longitudinal data set><longitudinal dataset><model organism><monocular><motoneuron><motor behavior><motor control><multi-modality><multimodality><neural><neural circuit><neural circuitry><neural control><neural regulation><neurocircuitry><neuromodulation><neuromodulatory><neuronal><neuroregulation><novel><ocular motor><ocularmotor><oculomotor><oculomotor behavior><optical><optogenetics><resolutions><response><sample fixation><social role><statistical analysis><synaptic circuit><synaptic circuitry><tool><two-photon><vertebrata><visual motor><visuomotor><working memory>