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Sensory-motor transformations in a neural circuit for object-directed walking

Award Number: R01NS143970
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/20/2026
PERIOD OF PERFORMANCE END DATE: 04/30/2031

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Sensory-motor transformations in a neural circuit for object-directed walking - Walking towards a salient object (prey, mate, etc.) is a basic and conserved behavioral motif shared across most terrestrial animals, including humans. Mobility disorders often impact this vital function of goal-directed walking. Despite varied evolutionary histories, both vertebrates and invertebrates have converged on similar leg- kinematics strategies to drive changes in walking speed and direction. Therefore, a mechanistic understanding of goal-directed walking, in any species, is critical and will have broad implications. Certain descending output pathways of the brain that project to the spinal-cord (vertebrates) or ventral-nerve- cord (invertebrates), have been shown to control specific aspects of leg movements required for directed walking. However, how sensory inputs, like those representing a potential mate, engage appropriate combinations of descending pathways to move the animal as intended, remains an open question. This gap is due to two major challenges: 1) defining a clearly resolved sensory-motor neural circuit underlying object-directed walking, and 2) measuring and perturbing combinations of descending pathways that govern the leg movements required for object-directed walking. We propose to overcome these challenges by using the well-established Drosophila model system. In the proposed work, we will evaluate how physiology and connectivity within a defined and genetically accessible, multi-layered neural circuit (the DNp09 input-output circuit) transform object-tracking sensory input into directed-walking output. To enable this, we developed new experimental and modeling approaches, that provide high-fidelity access to this neural circuit at cellular and synaptic resolution. We will first use whole-cell electrophysiological recordings and biophysically detailed full morphology models to examine how synaptic layout of specific visual pathways recruit the DNp09 network during object-directed turning events. We will then use novel calibrated stimulation techniques and connectome-constrained network models to characterize how DNp09 recruits a population of interconnected descending neurons that are poised to control directed walking. Through a combination of modeling and experiments leveraging two-photon holography and high-resolution kinematics analysis, we will then extract how descending neuron population activity states encode directed walking maneuvers. The proposed efforts will determine how sensory-evoked naturalistic activity propagates across a network of interconnected neurons to drive the distributed control of motor outputs required for generating object-directed walking. The long-term objective of this work is to provide cross-species transferable models of how combinations of brain output pathways orchestrate the downstream motor circuits for executing appropriate locomotor outputs, a fundamental problem in understanding how brains control behaviors.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $518,582 )
2026	2026	MAX PLANCK FLORIDA CORP	1 MAX PLANCK WAY	JUPITER	FL	33458	PALM BEACH	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	5/22/2026	NEW	$518,582
														Subtotal = $518,582

Grand Total All Awards = $518,582

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Sensory-motor transformations in a neural circuit for object-directed walking

Award Number: R01NS143970

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/20/2026

PERIOD OF PERFORMANCE END DATE: 04/30/2031

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