Neuronal circuits in the brainstem control life-sustaining functions, in addition to driving and gating active sensation through taste, smell, and touch. We propose to exploit the advent of molecular and genetic tools to undertake cell lineage marking, cell phenotyping, molecular connectomics, and methods from machine learning and image processing to construct an integrated anatomical and functional atlas of the brainstem. This will enable us to generate anatomical wiring diagrams for the brainstem circuits that control or facial actions. There are three phases to this work. (1) Reveal the identity and organization of brainstem nuclei. Motivated by striking similarities between the developmental plan for the spinal cord and brainstem, we will embrace and extend these efforts to interrogate the molecular composition of neurons that define individual nuclei with sensorimotor circuits in the murine brainstem. (2) Reveal brainstem neuronal circuits and their interactions. We will utilize Tran synaptic viral labeling to delimit pathways from specific muscles that are innervated by facial, trigeminal, hypoglossal, and laryngeal motor nuclei. This will reveal hitherto unknown brainstem circuits, including sites of modulation by higher brain areas. (3) Control the behavior of identified feedback circuits. We will manipulate specific populations of brainstem neurons using a battery of genetic tools to delineate or facial motor actions and motor synergies. The results from the above efforts will be a quantitative map of the functional organization of neurons in the brainstem that enable studies on computations that underlie or facial behavior. An understanding of these fundamental behaviors bears directly on the more general issue of how nervous systems deal with computations that can be performed autonomously, yet must interact synergistically. Thus our proposed program on brainstem circuitry and dynamics will yield general lessons about the nature of neuronal computation. The work performed under this proposal will serve as the basis for a larger national effort in brainstem neuronal computation.

Public Health Relevance

Neuronal circuits in the brainstem control life-sustaining functions, including breathing and or facial behaviors such as suckling and chewing that must be performed without interruption from the moment of birth. We will use the tools of modern molecular neuroscience to add informative labels to individual neurons in the brainstem, place these cells within circuits, and connect circuits with behavioral function. Our procedures and analysis will mitigate many of the difficulties that have limited our ability to discern the structre and function of brainstem circuits in normal and diseased states.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project--Cooperative Agreements (U01)
Project #
1U01NS090595-01
Application #
8827174
Study Section
Special Emphasis Panel (ZNS1-SRB-S (61))
Program Officer
Gnadt, James W
Project Start
2014-09-30
Project End
2017-07-31
Budget Start
2014-09-30
Budget End
2015-07-31
Support Year
1
Fiscal Year
2014
Total Cost
$851,597
Indirect Cost
$238,934
Name
University of California San Diego
Department
Physics
Type
Schools of Arts and Sciences
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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
Aljadeff, Johnatan; Lansdell, Benjamin J; Fairhall, Adrienne L et al. (2016) Analysis of Neuronal Spike Trains, Deconstructed. Neuron 91:221-59
Kleinfeld, David; Deschênes, Martin; Ulanovsky, Nachum (2016) Whisking, Sniffing, and the Hippocampal θ-Rhythm: A Tale of Two Oscillators. PLoS Biol 14:e1002385
Moore, Jeffrey D; Mercer Lindsay, Nicole; Deschênes, Martin et al. (2015) Vibrissa Self-Motion and Touch Are Reliably Encoded along the Same Somatosensory Pathway from Brainstem through Thalamus. PLoS Biol 13:e1002253
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
Deschênes, Martin; Haidarliu, Sebastian; Demers, Maxime et al. (2015) Muscles involved in naris dilation and nose motion in rat. Anat Rec (Hoboken) 298:546-53
Haidarliu, Sebastian; Kleinfeld, David; Deschênes, Martin et al. (2015) The Musculature That Drives Active Touch by Vibrissae and Nose in Mice. Anat Rec (Hoboken) 298:1347-58
Kleinfeld, David; Moore, Jeffrey D; Wang, Fan et al. (2014) The Brainstem Oscillator for Whisking and the Case for Breathing as the Master Clock for Orofacial Motor Actions. Cold Spring Harb Symp Quant Biol 79:29-39
Moore, Jeffrey D; Deschênes, Martin; Kurnikova, Anastasia et al. (2014) Activation and measurement of free whisking in the lightly anesthetized rodent. Nat Protoc 9:1792-802

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