CORE B. ADMINISTRATIVE CORE General anesthesia is a fascinating man-made, neurophysiological phenomenon that has been developed empirically over many years to enable safe and humane performance of surgical and non-surgical procedures. Specifically it is a drug-induced condition consisting of unconsciousness, amnesia, analgesia and immobility, along with physiological stability. General anesthesia is administered daily to 60,000 patients in the United States, the mechanisms for how anesthetics act in the brain to create the states of anesthesia are not well understood. Significant progress has been made recently in characterizing the molecular sites that anesthetics target. However, how actions at specific molecular targets lead to the behavioral states is less well understood. Addressing this issue requires a systems neuroscience approach to define how actions of the drugs at specific molecular targets and neural circuits lead to a behavioral state of general anesthesia. In this program project entitled, Integrated Systems Neuroscience Studies of Anesthesia, we will develop an integrated systems neuroscience program consisting of human, non-human primate, rodent and modeling studies of four anesthetics: the GABAA agents, propofol and sevoflurane; the alpha-2 adrenergic agonist, dexmedetomidine; and the NMDA receptor antagonist, ketamine. The program project will also include a DATA ANALYSIS CORE, which will provide assistant with data analysis and conduct research on statistical methods.
The Specific Aims are to understand how the actions of the anesthetics at specific molecular targets and neural circuits produce the oscillatory dynamics (EEG rhythms, changes in LFPs and neural spiking activity) that are likely a primary common mechanism through which anesthetics create altered states of arousal (sedation, hallucination, unconsciousness). This program project will be a unique research collaboration among anesthesiologists, neuroscientists, bioengineers, a neurosurgeon, a neurologist, a statistician and a mathematician at Massachusetts General Hospital and Boston University. The day-to-day management of this program project will require an active team of support staff to accomplish its several goals. The responsibilities of the administrative core will include day-to-day administrative and financial management, along with planning of bi- weekly program project meetings, bi-weekly Executive Committee meetings, and planning of the annual Scientific Advisory Committee meeting.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
5P01GM118269-02
Application #
9430433
Study Section
Special Emphasis Panel (ZGM1)
Project Start
Project End
Budget Start
2018-02-01
Budget End
2019-01-31
Support Year
2
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02114
Song, Andrew H; Kucyi, Aaron; Napadow, Vitaly et al. (2017) Pharmacological Modulation of Noradrenergic Arousal Circuitry Disrupts Functional Connectivity of the Locus Ceruleus in Humans. J Neurosci 37:6938-6945
Flores, Francisco J; Hartnack, Katharine E; Fath, Amanda B et al. (2017) Thalamocortical synchronization during induction and emergence from propofol-induced unconsciousness. Proc Natl Acad Sci U S A 114:E6660-E6668
Akeju, Oluwaseun; Brown, Emery N (2017) Neural oscillations demonstrate that general anesthesia and sedative states are neurophysiologically distinct from sleep. Curr Opin Neurobiol 44:178-185
Guidera, Jennifer A; Taylor, Norman E; Lee, Justin T et al. (2017) Sevoflurane Induces Coherent Slow-Delta Oscillations in Rats. Front Neural Circuits 11:36