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Principal Investigator: Martha W Bagnall
Organization: WASHINGTON UNIVERSITY
Fiscal Year: 2024
Award: $377,088
Funding agency: National Institute of Neurological Disorders and Stroke
Project Summary
As animals locomote, they constantly coordinate activity between the rostral and caudal ends of the body. This
coordination relies on neurons in the spinal cord that send long ascending or descending axonal projections.
Although several studies have shown that ablation of these neurons leads to deficits in coordination, it is
largely unknown whether these long-range circuits are similar or different from local circuits. In recently
published data in larval zebrafish, we demonstrated that at least one genetically defined class of spinal
neurons, the V1 (En1+) population, changes its synaptic targets as its axon ascends in the spinal cord.
Specifically, V1 neurons form synaptic connections with motor neurons and other ventral horn neurons nearby,
but switch to inhibiting a dorsal horn sensory population at longer range. Here we propose to extend this
analysis to five additional sets of ventral horn neurons, the dI6, V0 excitatory and inhibitory, V2a, and V2b
populations. To create this large-scale circuit map, we use localized optogenetic activation of identified spinal
populations while carrying out whole-cell recording of identified potential postsynaptic partners. By translating
the optogenetic stimuli up and down the spinal cord, we can build a physiological map of the strength of the
synaptic connection at various rostrocaudal positions. Normalization of the synaptic charge transfer allows
comparisons across target populations, providing a comprehensive grid of connectivity among spinal neuron
classes at various rostrocaudal distances. We will then build a computational model of spinal cord connectivity
that reflects biological reality, as measured in these experiments. Using this model, we will test the
consequences of shifting synaptic connections in the rostrocaudal axis, in order to understand the logic of
spinal circuit organization. Finally, we will selectively ablate long-range or local V2a neurons to determine the
behavioral effects of long-range vs local projections. Together, these experiments will provide a circuit map of
genetically identified spinal neurons.
Terms: <Ablation><Animals><Anterior Horn Cells><Anterior Horn Neurons><Assay><Axon><Behavioral><Bioassay><Biological><Biological Assay><Brachydanio rerio><Charge><Clinical><Computer Models><Computerized Models><Contralateral><Danio rerio><Data><Enhancer-Binding Protein GATA3><Ensure><Exhibits><GATA-3 factors><GATA-3 protein><GATA-Binding Protein 3><GATA3><GATA3 gene><GATA3 protein><GATA3 transcription factor><Head><Home><Horns><Injury><Ipsilateral><Leg><Locomotion><Logic><Mammalia><Mammals><Maps><Measures><Medulla Spinalis><Modeling><Morphology><Motor><Motor Cell><Motor Neurons><Movement><Muscle Cell Contraction><Muscle Contraction><Muscular Contraction><Natural regeneration><Nerve Cells><Nerve Unit><Neural Cell><Neurocyte><Neurons><Organism><Output><Pattern><Physiologic><Physiological><Population><Position><Positioning Attribute><Publishing><Regeneration><Sensory><Slice><Spinal><Spinal Cord><Stimulus><Structure><Synapses><Synaptic><Synaptic Potentials><Tail><Target Populations><Testing><Translating><V1 neuron><Ventral Horn Cells><Ventral Horn Neurons><Vertebrae><Vertebral><Walking><Whole-Cell Recordings><Work><Zebra Danio><Zebra Fish><Zebrafish><arm><biologic><body movement><computational modeling><computational models><computer based models><computer based prediction><computerized modeling><dorsal horn><experiment><experimental research><experimental study><experiments><homes><in vivo><inhibitory neuron><injuries><living system><motoneuron><neuronal><optogenetics><postsynaptic><predictive modeling><regenerate><spinal cord repair><spine bone structure><synapse>