Pre-motor Neural Circuits for Exploratory Movement Abstract Movements performed by animals in order to explore external objects are called exploratory movements. Humans use delicate and complex movements of fingers/fingertips to discern the texture, shape and other physical properties of objects, and to manipulate tools. Rodents explore their physical environment through rhythmic sweeping of their vibrissae (whisking), and thus serve as a major model for studying neural circuits controlling exploratory touch movements. The final common control of the tactile vibrissae is provided by motor neurons located in the lateral facial nucleus (vFMNs). The objective of this proposal is to discover and characterize the premotor circuitry that directly regulates the activities of vFMNs. We will identify the connectivity maps of premotor neurons that provide monosynaptic input for the different vFMNs controlling vibrissa protraction and retraction. We wil also determine the neurotransmitter phenotypes of identified premotor neurons, and characterize the functional inputs of different premotor neurons onto vFMNs using electrophysiological and optogenetic approaches. Furthermore, we will determine how developmental changes in the vFMN premotor circuitry enable the postnatal emergence of bilaterally coordinated and often synchronized exploratory whisking behavior. Identifying the structural and functional wiring diagram of these premotor neural circuits is a critical step for investigating the generation and voluntary control f exploratory movements. Results from this study will also provide new foundations for understanding motor control of hand and finger movements in humans, and thus can help lead to the design of superior neuroprosthetics devices to restore exploratory movements following paralysis or amputation.

Public Health Relevance

This proposal uses newly developed monosynaptic rabies virus based trans-synaptic tracing methods combined with electrophysiology and optogenetics to precisely identify and characterize the premotor neural circuits that control exploratory 'activ touch' movements in mouse. Understanding neural circuits generating and controlling active touch movements will help design better neuroprosthetics for amputated or paralyzed patients. It is also expected that results obtained from this study will lead to the discovery of neural circuits for sensorimotor integration underlying complex movements, which is relevant to treating a wider range of neurological disorders in which the sensorimotor loop is damaged.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS077986-03
Application #
8791925
Study Section
Sensorimotor Integration Study Section (SMI)
Program Officer
Gnadt, James W
Project Start
2013-02-15
Project End
2018-01-31
Budget Start
2015-02-01
Budget End
2016-01-31
Support Year
3
Fiscal Year
2015
Total Cost
$333,793
Indirect Cost
$115,043
Name
Duke University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
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Lu, Jinghao; Li, Chunyuan; Singh-Alvarado, Jonnathan et al. (2018) MIN1PIPE: A Miniscope 1-Photon-Based Calcium Imaging Signal Extraction Pipeline. Cell Rep 23:3673-3684
Takatoh, Jun; Prevosto, Vincent; Wang, Fan (2018) Vibrissa sensory neurons: Linking distinct morphology to specific physiology and function. Neuroscience 368:109-114
Bellavance, Marie-Andrée; Takatoh, Jun; Lu, Jinghao et al. (2017) Parallel Inhibitory and Excitatory Trigemino-Facial Feedback Circuitry for Reflexive Vibrissa Movement. Neuron 95:673-682.e4
Deschênes, Martin; Kurnikova, Anastasia; Elbaz, Michael et al. (2016) Circuits in the Ventral Medulla That Phase-Lock Motoneurons for Coordinated Sniffing and Whisking. Neural Plast 2016:7493048
Deschênes, Martin; Takatoh, Jun; Kurnikova, Anastasia et al. (2016) Inhibition, Not Excitation, Drives Rhythmic Whisking. Neuron 90:374-87
Sakurai, Katsuyasu; Zhao, Shengli; Takatoh, Jun et al. (2016) Capturing and Manipulating Activated Neuronal Ensembles with CANE Delineates a Hypothalamic Social-Fear Circuit. Neuron 92:739-753
Stanek 4th, Edward; Rodriguez, Erica; Zhao, Shengli et al. (2016) Supratrigeminal Bilaterally Projecting Neurons Maintain Basal Tone and Enable Bilateral Phasic Activation of Jaw-Closing Muscles. J Neurosci 36:7663-75
Kim, Il Hwan; Rossi, Mark A; Aryal, Dipendra K et al. (2015) Spine pruning drives antipsychotic-sensitive locomotion via circuit control of striatal dopamine. Nat Neurosci 18:883-91
Matthews, David W; Deschênes, Martin; Furuta, Takahiro et al. (2015) Feedback in the brainstem: an excitatory disynaptic pathway for control of whisking. J Comp Neurol 523:921-42

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