Movements performed by animals in order to explore external objects are called exploratory movements. The rodent whisker-mediated tactile exploration is a prominent model of exploratory movements. It is known that fast sensory feedback, attention, memory and other factors modulate the patterns of whisker movements in different behavioral contexts. However, the precise neural circuits mechanisms that mediate such task- or context-dependent control of whisker movement patterns remain largely unknown. Through our monosynaptic whisker premotor circuit mapping studies and on-going functional characterizations, we have now identified a group of premotor neurons mediating a sensory feedback reflex, and also discovered the putative premotor whisking oscillator (rhythmogenic) neurons. The goal of this competitive renewal is to determine the in vivo activity patterns of these identified premotor neurons (sensory feedback and the rhythmogenic premotor neurons) in different behavior contexts, mapping their presynaptic inputs (i.e. identifying pre-premotor neurons, or pre2motor neurons) and begin to unveil how key pre2motor neurons convey context-dependent modulation of whisker movements. We will use a combination of viral genetic intersectional labeling strategy, in vivo optetrode-array based recording of photo-identified premotor neurons, modeling, non-toxic viral mediated transsynaptic labeling and manipulation of pre2motor neurons in multiple behavioral tasks to achieve our goal.

Public Health Relevance

! This proposal combines modern viral-genetic labeling and transsynaptic circuit mapping, optogenetic manipulation, and in vivo extracellular recording from identified neurons to reveal neural mechanisms regulating sensory feedback, rhythmogenesis, and context-dependent control of exploratory tactile movements. The results from this proposal are expected to advance our understanding motor control circuits, and eventually help uncover abnormal neural circuits associated with movement disorders, sensorimotor integration deficits, and tactile agnosia, and potentially aid the design and development of better neuroprosthetics for patients with motor dysfunctions.!

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
7R01NS077986-09
Application #
10348340
Study Section
Sensorimotor Integration Study Section (SMI)
Program Officer
David, Karen Kate
Project Start
2013-02-15
Project End
2023-06-30
Budget Start
2021-02-09
Budget End
2021-06-30
Support Year
9
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Type
DUNS #
001425594
City
Cambridge
State
MA
Country
United States
Zip Code
02142
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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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