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Lecture 8

HMB200 2014 Lecture 8.pdf

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Human Biology
John Yeomans

  Lecture  8:  Sleep  and  Arousal   Diffuse  Arousal  Systems   - Most  of  the  cortical  arousal,  most  of  the  REM  sleep  arousal,  and  most  of  the  sleep  changes  are  generated  by   neurons  in  the  midbrain  and  pontine  region   - Arousal  that  happens  (that  activates  dopamine  systems)  is  associated  with  the  arousal  that  happens  with  cortical   activation     - EEG  changes  that  occur  during  waking  ar ousal  are  closely  related  to  EEG  changes  that  happen  during  REM  sleep   - Connected  by  diffuse  arousal  systems   norepinephrine  neurons  in  locus  coeruleus  (A6)   • Norepinephrine  neurons  in  locus  coeruleus  produce  wide  spread  activation  on  the  entire  cortex   - These  are  just  above  the  mesopontine  cholinergic  neurons  (critical  in  RE M  sleep,  waking  arousal,   activating  dopamine  systems,  and  rewards  and  drug  abuse)   - Locus  coeruleus  neurons  are  widespread  in  brain  stem   à  A6  group  goes  to  the  cortex   mesopontine  cholinergic  neurons  (Ch5,  6)   Raphe  Serotonin  Neurons  (B5,  6)   • Serotonin  neurons  in  the  Raphe  Nuclei   Histamine  neurons  in  Posterior  Hypothalamus   Orexin/Hypocretin  neurons  in  Lateral  Hypothalamus   Basal  Forebrain  Cholinergic  Neurons  (Ch1 -­‐4)   • Cholinergic  neurons  in  midbrain -­‐pons  border  which  go  to  thalamus  to  produce  thalamic  activation,   go  to  the  basal   forebrain  cholinergic  neurons  that  produce   diffuse  cortical  activation   All  active  in  waking  arousal     Cholinergic  Arousal  Systems  (Ch1 -­‐6)   - If  u  record  form  norepinephrine,  serotonin,  acetylcholine   - Active  during  waking   - Less  active  during  slow  wave  sleep   - Very  quiet  during  REM  sleep   - Serotonin  and  norepinephrine  are  very  quiet  during  REM  sleep   - As  you  go  deeper  and  deeper  in to  sleep,  they  become  less   active   - Only  exception:  25%  of  ACh  neurons  are  intensity  active   during  REM  sleep  (REM-­‐on  neurons)  à  from  less  active  to  a   burst  of  activity  just  before  REM  sleep  begins   - Proposed  cholinergic  (REM  on  neurons)  trigger  arousal     -  Cholinergic  arousal  neurons  produce  a  lot  of  activation   (produce  thalamic  activation  –  cortical  arousal,   produce  basal  forebrain  a ctivation  –  cholinergic   arousal)   - Have  ability  to  turn  on  cortex   - REM-­‐on  neurons  do  similar  thing  during  sleep  states   à  turn  on  basal  forebrain  and  thalamus   à  result  in   widespread  cortical  arousal  (produce  beta  and  gamma  waves ,  producing  widespread  cortical  activation)   - Slightly  different  only  REM -­‐on  neurons  that  are  doing   this     Model  of  REM  Sleep  Systems   - dorsal  pontine  area  is  very  important  in  coma   - Most  people  who  are  in  a  coma   –  have  damaged  to   dorsal  pontine  area   - Coma  =  prolonged  unconsciousness   - usually  caused  by  injury  to  the  dorsal  pontine  reticular   formation   - dorsal  pons  is  right  below  the  cerebellum     EEG  and  Sleep   - Brain  waves  have  dramatic  changes  during  sleeping   states   Ø Waking  Alpha  (10Hz)  and  Beta/Gamma  waves  (40  Hz)       - Waking:  when  relaxed  there  is   steady  and  reliable  10  Hz  wave  (called  alpha)   –  alpha  waves  are  easy  to  see  by   recording  with  electrodes  on  surface  of  scalp   –  10  peaks  every  second  (peaks  are  very  steady  and  reliable   especially  in  occipital  cortex)   - have  to  be  amplified  –  they  are  low  amplitude   - alpha  waves  change  when  you  get  excited  =  beta  waves   à  beta  waves  divided  into  beta  and  gamma   àbeta  is  under  40hz   à  Gamma  over  40hz   à  High  frequency,  low  amplitude,  and  irregular  waves   Ø waking  states  involve  relaxed  alpha  waves,  and  more  intensely  ac tive  beta  and  gamma  waves  (high  frequency  and   lower  amplitude)   Ø represent  the  average  EPSP  (slow  waves  inside  neurons)   Ø Slow-­‐wave  sleep:  from  alpha  to  spindles  (14  Hz)  and  delta  (1 -­‐4Hz)   Ø as  you  fall  asleep,  you  go  into  alpha,  then   spindles,  then  really  slow  waves  (delta)   Ø As  people  fall  asleep,  they  swit ch  to  slow   wave  sleeps  (stage  1,   2,  3,  and  4)   à  alpha  in  stage  1   à  spindles  in  stage  2  and  3   à  delta  in  stage  4   Ø REM  sleep:  cortical  arousal  and  muscular   atonia  à  also  called  paradoxical  or  dream   sleep   - high  cortical  arousal  –  indicated   by  gamma  waves   -­‐ Slow  wave  sleep  to  rem  sleep  every  45   min   -­‐ profound  muscular  quiescence   à   muscles  very  relaxed  more   than   any  other  time  (muscular  atonia  à   all  motor  neurons  in  body  are   inhibited  (except  eye  muscles))   -­‐ Eye  muscles  moving  quickly     -­‐ Moving  without  disrupting  sleep   -­‐ Large  muscles  inhibited  so  that  you   don’t  wake  your  self  up  when   dreaming   -­‐ Paradoxical:  eye  moving  around,  brain  being  so  chaotic,  body  so  quiet   Ø Triggered  by  pontine  reticular  formation  neurons  by   ACh  and  other  signals   - Epileptic  Seizures:  synchronous  cortex  activity   - Pontine  Reticular  Formation:  Norepinephrine,  Serotonin,  ACh   - These  neurons  go  from  active  during  waking,  to  less  active  during  slow  wave  sleep,  to  very  quiet  during   REM  sleep     As  You  Fall  Asleep   - Awake  to  slow  wave  sleep   - As  you  progress  through   stage  1  -­‐2  -­‐3  -­‐4   - waking  and  gamma  are  irregular  and   low  amplitude,  high  frequency   - alpha  is  steadier  and  higher   amplitude   - As  you  get  into  sleep  and  now  unconscious,   brain  waves  become  slower  and  slow er   - In  stage  2,  alpha  waves  are  interrupted  by   14hz  sleep  spindles  à  very  rare,  dominated   by  alpha  à  bursts  in  sleep  spindles   - Stage  3  and  4:  very  slow  and  irregular  =  delta   slow  waves       - Stage  4:  dominated  by  delta  waves,  high  amplitude   and  very  irregular  waves  (one  peak  every  second   –  1  to  4  Hz)  à   deepest  part  of  slow  wave  sleep  (1/2  hour  after  you  fall  asleep)   - REM  SLEEP:  As  if  body  is  awake,  muscles  are  quiet  (atonia)     -­‐  but  you  are  unconscious   • Have  an  increase  in  gamma  waves  that  interrupt  slow  wave  slee p   • Very  high  amplitude  to  very  low  amplitude  and  high  frequency  waves  (as  if  you  woke  up)   • Fast  wave  sleep   • in  the  middle  of  deepest  sleep   • hard  to  wake,  if  awoken,  they  remember  their  dreams   • REM  sleep  =  dream  sleep   • high  frequency  waves:  intense  cortical   activity  –  dreaming  occurrence   • correlation  between  rapid  eye  movement s  and  dream  states   o eye  movements  consistent  with  the  dream   • 4-­‐5  REM  peaks  in  a  typical àni  interrupted,  and  longer  in  duration  as  you  go  from  first  REM  to  last   o the  whole  night,  you  rotate  between  slow  wave  and  REM  sleep  (only  lasts  a  few  minutes)  every  90   minutes     REM  Sleep   - brain  is  active,  and  eyes  are  active   - muscles  of  body  are  profoundly  inhibited  (atonia)   - subjects  report  dreams  when  awoken   - NE  and  5HT  neurons  go  silent.  Many  Ch  neuron s  become  active   - In  slow-­‐wave  sleep,  brain  and  eyes  are  quiet,  but  muscles  are  more  active   - Functions  of  sleep  and  dreams?     Brain  Areas  –  Early  Studies   - Dorsal  pon  are  right  below  cerebellum   - Shelf  above  the  cerebellum   coma  (prolonged  unconsciousness)  due  to  i njury  in  dorsal  reticular  formation   - Blow  to  back  of  head  à  pushes  into  dorsal  pons  à  hard  shell  between  cerebellum  and  cortex   punctures   into  dorsal  pontine  region  à  damages  arousal  neurons  –  which  triggers  cortical  arousal   (combination  of   dorsal  pontine  areas  that  cause  coma)   - Constant  unconsciousness  is  due  to  the  inability  to  produce  cortical  arousal  by  way  of  these  several   different  diffuse  ascending  systems   stimulation  of  Reticular  Formation  leads  to  arousal   - reticular  formation  activation  can  trigger  a rousal  of  entire  cortex   - can  turn  arousal  on  or  off  by  da maging  or  activating  this  area   - dorsal  pontine  region  is  the  critical  area  for   widespread  cortical  activation   ascending  path  for  cortical  arousal   - Must  be  an  ascending  pathway   from  this  dorsal  pontine  reticular  formation  that  causes  cortical  arousal   descending  path  for  atonia   critical  area:  dorsal  pontine  reticular  formation   - Atonia:  descending  pathway  to  motor  neurons   - Motor  neurons  of  neck,   head  and  all  of  body  spinal  cord  motor  neurons  à  go  into  a  state  of  total   quiescence  (must  be  a  descending  pathway  that  results  in  profound  inhibition)   à  glycine  or  GABA  are   important  inhibitors   - This  descending  pathway  comes  from  same  general  region  of  dorsal  pons   - Some  set  of  neurons  in  pontin e  area  result  in  2  effects:   1) 1  major  ascending  pathway   –  such  as  cholinergic  neurons  that  activates  thalamus  and  these  basal  forebrain   neurons  –  results  in  widespread  cortical  activation  by  way  of  ascending  cholinergic  pathways   2) 2  sets  of  hypothalamic  neuron s  that  are  part  of  this  cortical  activation:   a. Histamine  neurons  in  posterior  thalamus   –  tiny  little  cluster  neurons  called  tuberomammillary   histamine  neurons  (about  3000  neurons  clustered  in  the  posterior  hypothalamus)   - Have  widespread  cortical  arousal   effects   b. Just  in  front  of  these,  in  lateral  hypot
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