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…

The National Institute of Neurological Disorders and Stroke awarded Max Planck Florida Corp (doing business as Max Planck Florida Institute For Neuroscience) $518,582 in project grant funding on May 20, 2026, under the Extramural Research Programs in the Neurosciences and Neurological Disorders program (CFDA 93.853).

The award funds investigation of sensory-motor transformations in neural circuits controlling object-directed walking in Drosophila melanogaster. The research examines how visual and other sensory inputs engage descending neural pathways to produce coordinated leg movements required for walking toward salient objects. The principal investigator and team will use whole-cell electrophysiological recordings and biophysically detailed full-morphology computational models to analyze how the synaptic architecture of visual pathways recruits the DNP09 neural circuit at cellular and synaptic resolution, then measure and perturb combinations of descending pathways governing the leg movements necessary for directed walking. The work is performed at Jupiter, Florida over a period of performance from May 20, 2026 through April 30, 2031.

Drexel University serves as a sub-recipient, with Dr. Jessica Ausborn's computational neuroscience group developing data-driven biophysically accurate multi-compartment and reduced neuron models of the object-directed walking circuit. Ausborn's team will build network models to simulate activity states of key neurons in response to ethologically relevant stimuli, conduct connectomics analysis using electron microscopy datasets of the fruit fly brain and ventral nerve cord, and perform synaptic topography analyses in close collaboration with the prime investigator, Dr. Salil Bidaye, throughout the award period.

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.