Principal Investigator: David Kleinfeld
UCSD Neuroscience
Title: “Revealing the connectivity and functionality of brain stem circuits”
BRAIN Category: Understanding Neural Circuits (RFA NS-14-009)
Dr. Kleinfeld and his colleagues will use a variety of tools and techniques to create detailed maps of circuits in the brainstem, the region that regulates many life-sustaining functions such as breathing and swallowing, and match the circuits to actions they control.
Project Description
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 Statement
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.
NIH Spending Category
Dental/Oral and Craniofacial Disease; Mental Health; Neurosciences
Project Terms
Area; Atlases; Automobile Driving; base; Behavior; Behavior Control; Behavioral; Biological Assay; Birth; Brain; Brain Stem; Breathing; Cell Lineage; Cell Nucleus; cell type; Cells; Collaborations; Comparative Anatomy; Complex; Computer Simulation; computer studies; Data Analyses; Development; Embryonic Development; Employee Strikes; Engineering; Equilibrium; Esthesia; Face; Feedback; feeding; Functional Imaging; Genetic; Genetic Programming; Group Meetings; Image; image processing; Imagery; Individual; insight; Interruption; Jaw; Joints; Label; Larynx; Life; Machine Learning; Maps; Mastication; Methods; Molecular; Molecular Biology; Molecular Genetics; molecular phenotype; Motor; Motor output; Movement; multidisciplinary; Mus; Muscle; Nature; Neck; neonate; nerve stem cell; Nervous system structure; Neuroanatomy; Neurons; Neurosciences; Nociception; orofacial; Pathway interactions; Pattern; Phase; Physiology; Population; Procedures; Process; programs; public health relevance; Publications; Recording of previous events; Rodent; Scheme; Sensory; Signal Transduction; Site; Smell Perception; Spinal; Spinal Cord; Synapses; System; Tactile; Taste Perception; Technology; Theoretical Studies; Tongue; tool; Touch sensation; Trigeminal System; Ursidae Family; Viral; visual tracking; vocalization; Work