The Role of the Rostromedial Tegmental Nucleus (RMTg) in Modulating NREM Sleep and Anesthetic-Induced Unconsciousness

鼻内侧被盖核 (RMTg) 在调节 NREM 睡眠和麻醉引起的无意识中的作用

• 批准号: 10221589
• 负责人: Olivia Ann Moody
• 金额: $ 3.06万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2022-05-06
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10221589
• 关键词: American; Anesthesia procedures; Anesthetics; Arousal; Automobile Driving; Behavioral; Behavioral Assay; Brain; Brain Stem; Cardiovascular system; Cell Nucleus; Coma; Conscious; Consciousness Disorders; Dopamine; Drug Receptors; Electroencephalogram; Electromyography; Equilibrium; General Anesthesia; General anesthetic drugs; Goals; Grant; Histology; Impaired cognition; Inhalation Anesthesia; Intravenous Anesthetics; Investigation; Knowledge; Manuscripts; Measures; Midbrain structure; Minor; Neurologic; Neurons; Operative Surgical Procedures; Paper; Pathway interactions; Patients; Physiological; Play; Preoptic Areas; Publishing; Rattus; Research; Research Personnel; Respiratory System; Rodent; Role; Scientist; Sleep; Sleep Disorders; Sleep Wake Cycle; Slow-Wave Sleep; System; Time; Training; Transgenic Organisms; Unconscious State; Ventral Tegmental Area; Wakefulness; Writing; Yang; career; design; designer receptors exclusively activated by designer drugs; dopaminergic neuron; gamma-Aminobutyric Acid; in vivo; neural circuit; neuronal circuitry; neurophysiology; neurotransmission; non rapid eye movement; novel; pressure; relating to nervous system; side effect; skills; symposium; tool; trait

PROJECT SUMMARY/ABSTRACT  The neural  circuits that  induce and  maintain  anesthetic-­induced  unconsciousness  remain  incompletely  understood. Given that anesthesia and sleep are both forms of reversible unconsciousness, anesthesia research  has  investigated  whether  sleep  circuits  in  the  brain  regulate  anesthetic-­induced  unconsciousness.  However,  studies  of  the  preoptic  area,  which  contains  the  main  sleep  centers  in  the  brain,  do  not  explain  all  aspects  of  anesthetic-­induced  unconsciousness,  leading  researchers  to  look  for  new  brain  circuits.  A  newly  discovered  midbrain nucleus, the rostromedial tegmental nucleus (RMTg), sends major GABAergic projections to the ventral  tegmental area  (VTA).  Altering  the activity  of dopaminergic neurons  in  the VTA  has  been previously  shown  to  induce  emergence  from  continuous  inhaled  anesthesia,  suggesting  a  role  of  midbrain  circuits  in  regulating  anesthetic-­induced unconsciousness. To date, only one paper has begun studying the role of the RMTg in sleep,  and no papers have yet looked at its role in anesthesia. This proposal will fill this gap and provide new information  about  a  midbrain  nucleus  that  may  regulate  different  states  of  consciousness.  The  central  hypothesis  of  this  proposal  is  that  altering  the  activity  of  the  GABAergic  RMTg  neurons  will  impact  the  brain’s  sensitivity  to  anesthetics. We will use transgenic rats expressing Designer Receptors Exclusively Activated by Designer Drugs  (DREADDs) to specifically activate or inhibit GABAergic neurons of the RMTg. Aim 1 will investigate the impact  of  altering  the  RMTg’s  activity  on  NREM  sleep  using  electroencephalogram  (EEG)  recordings.  Aim  2  will  use  rodent behavioral assays  and  in  vivo EEG  and  local  field  potential  (LFP)  recordings  to determine  the extent  to  which the RMTg’s activity influences anesthetic sensitivity. The results from this proposal will characterize a new  circuit  that  may  modulate  reversible  unconsciousness  in  the  brain.  Understanding  novel  circuits  involved  in  regulating different states of consciousness will generate new knowledge that could help develop new treatments  for  various  disorders  of  consciousness,  including  neurological  sleep  disorders  and  minimally  consciousness  patients.  Understanding  the  neural  circuits  involved  in  producing  anesthesia  could  also  help  scientists  design  more  specific  anesthetics  that  have  fewer  physiological  side  effects  on  systems  like  the  respiratory  and  cardiovascular systems.

项目总结/文摘