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Lecture 9

HMB200 2014 Lecture 9.pdf

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Human Biology
John Yeomans

  Lecture  9:  Circadian  Rhythms   - all  animals  adapt  behavior  to  light  cycle   - Nocturnal  vs.  diurnal  strategies   - To  be  up  when  there’s  light  and  the  organism  can  see  things   - Use  light  cycle  to  find  animals   - If  you’re  a  rat/preyed  up  by  large  animals   à  take  a  different  strategy  à  come  out  at  night  where  there  are   fewer  predators  (diurnal  =  more  vulnerable,  nocturnal  =  allows  rat  to  get  food  in  a  safer  environment)   - All  plants  and  animals  have  internal  clocks  to  maintain  their  metabolic  and  behavioral  rhythms   - All  plants  use  internal  signals  to  respond  to  light   à  these  internal  signals  adapt  their  life  cycles  to  day  or   night   - These  internal  clocks  (found  in  plants,  primitive  one  cell  animals,  and   complex  animals  –  all  mammals)   involve  special  mechanisms  of  light  detection,  and  activity  and  metabolic  generation   - Clocks  must  be  influenced  by  light,  and  must  work  together  to  coordinate  metabolism  and  behavior   - Internal  clocks  allow  these  organism  to  adjust  to  solar  cycle   à  these  internal  clocks  must  be  influenced  by   light,  and  they  must  also  have  their  internal  rhythms  so  they  can  coordinate  activity  with  light  (adjust  by   way  of  light  =  entrainment)     - Also  need  to  be  able  to  maintain  this  rhythm  when  its  dark   - All  cells  in  the  body  have  to  have  an  internal  clock  that  allo ws  them  to  adapt  to  the  external  signals,  which   then  allows  them  to  adapt  their  internal  feeding  and  metabolic  cycles  to  the  entire  behavioral  cycle  (based   on  solar  cycle)   - Liver:  adjusts  the  metabolism  and  catabolism  of  all  our  energy  supplies   à  energy  we  use  depends  strongly  on  time   of  day   - Heart:  generation  of  energy  for  the  beating  of  the  heart  also  depends  on   the  light  cycle   - In  higher  animals,  there  are  clusters  of  cells  that  respond  to  light  à  can  also  continue  the  24hr  circadian  cycle  by   having  their  own  internal  rhythms   - These  internal  rhythms  are  determined  by  a  small  number  of  internal  clock  genes   - These  internal  clock  genes  are  very  similar  in  flies,  rodents,  and  humans   à  very  strongly  preserved  across   all  animals   - These  clock  genes  influenc e  when  we  are  active,  quiet  and  sleep,  and  also  all  metabolic  rhythms  of  the   body   - Circadian  rhythm  in  mammals:  controlled  by  the  suprachia smatic  nucleus   - Circadian  rhythm  in  birds:  controlled  by  the  pineal  glands         Measuring  Rhythms  in  Hamsters   - circadian  rhythm  in  hamsters:  hamsters  wake  up  very   intensely  at  the  same  time  everyday   - have  a  very  stable  circadian  rhythm  that  can  be  easily   monitored  during  by  turning  the  lights  out   - as  soon  as  the  light  turns  out:  they  go  from  sleeping,  to   becoming  intensely  active  in  just  minutes   - that  intense  waking  up  (when  its  dark)  =  you  can  see  them   running  (on  the  wheel)  as  soon  as  lights  are  turned  off   - connect  the  wheel  to  a  pen  and  paper   –  every  time  the   wheel  goes  around,  there  is  a  bar  that  activates  a  pen   à  if   that  pen  is  pushed  across  a  continuously  moving  piece  of   paper,  every  time  the  wheel  goes  around  once  =  line  on  the   moving  paper   - every  time  the  animal  moves,  you  get  a  horizontal  line   - over  24hr,  you  see  that  the  horizontal  lines  are  all  spaced   together  during  the  active  12  hours   - start  of  this  intense  activity  can  be  se en  by  when  the  first  peak  is  seen  on  the  paper   - take  the  paper  and  cut  it  –  cut  every  24  hours  =  rhythm  is  always  in  the  middle  of  the  day  (when  lights  are  off)   - by  aligning  each  day,  you  can   follow  how  the  circadian  rhythm  works  over  time         Circadian  Rhythms   - Endogenous  clock:  measured  in  constant  conditions,  still  23 -­‐25  hours  “free  running”   - if  you  put  humans/rodents  in  a  constant  dark  (humans  in  a  cave)  you  find  out  that  in  spite  light  has   been   removed,  these  animals  can  maintain  an  activity  rhythm   - this  activity  rhythm  is  not  exactly  24  hours,  some   animals  have  23  hours,  some  have  25  hours   - the  duration  depends  on  how  bright  the  light  is   - the  “free  running  period”  can  change  as  a  function     - all  animals  have  a  range  between  23 -­‐25  hours  to  maintain  a   rhythm   - Free  Running  24.1hr:  the  mean  free  running  time  for  hamsters:  was   very  close  to  a  day  (24.1  hours  on  average)   - No  Rhythm:  Rhythm  is  lost  when  Suprachiasmatic  Nucleus  lesioned  in   mammals,  or  pineal  gland  in  birds   - Birds:  Pineal  gland  is  at  the  back  of  the  epithalamus   - Mammals:  underside  of  the  thalamus  in  the  Suprachiasmatic   nucleus   - Rhythm  is  totally  lost  à  instead  of  intense  activity,  it’s  a  much   lower  activity   - Random  periods,  no  circadian  pattern   at  all   - Less  active  on  average  with  no  rhythm   - Suprachiasmatic  nucleus  is  important  for  maintaining  the   endogenous  circadian  rhythm   - Lesions  in  pineal  gland  shows  that  the  pineal  gland  is   necessary  for  circadian  rhythms  in  birds   - Suprachiasmatic  nucleus  is  also   the  place  where  the  rhythm  is  made,  and  it’s  the  master  clock  for  controlling  circadian   activity  rhythms  in  mammals   - Rhythm  is  restored  by  transplanting  new  SCN   –  period  of  donor  SCN   - Once  Suprachiasmatic  nucleus  cells  are  tra nsplanted,  rhythm  is  restored   - Tau  mutant  hamster  has  20hr  rhythm   - Odd  rhythm   - Hamster  who  is  heterozygous:  22  hr   rhythm   - Tau  =  time  constant  of  the  circadian   rhythm   - A  single  casein  kinase  gene  causes  tau   mutation  à  influences  turnover  of   proteins  in  the  cells  of  the   Suprachiasmatic  nucleus   - Takes  a  while  for  the  transplant  of  tau  to   the  SCN  to  start  working  (almost  no  effect   on  the  first  10  days)   - Transplanted  rhythm  is  slightly  below  20   hours,  19.8hr   - Rhythm  of  the  transplanted   Suprachiasmatic  nucleus  à  donor  controls  the  host   - This  tiny  transplant  can  take  over   rd - Transplant  was  put  into  the  base  of  the    ventricle  à  influences  the  animal,  host  uses  the  donors   rhythm  (independent  of  the  hosts  circadian  rhythm)   - Donors  rhythm  is  sufficien t  to  control  the  entire  endogenous  circadian  rhythm   à  coming  from  the   Suprachiasmatic  nucleusà  necessary  for  the  rhythm,  dominates  and  controls  it  =  master  clock  =   endogenous  clock  for  activity   - The  same  casein  kinase  gene  that  causes  tau  mutations  in  hamsters,  also  controls  humans   - If  humans  have  mutations,  they  will  also  have  abnormal  rhythms   - Same  casein  kinase  gene  that  controls  whether  you  have  a  shorter  or  longer  rhythm  in  humans   - Therefore,  SCN  is  endogenous  clock  for  activity     Retinal  Paths  to  SCN  and   IGL   - the  Suprachiasmatic  nucleus  is  in  the  hypothalamus,  just  above  the  crossing  fibers  of  the  optic  nerve  and  optic  tract       - these  fibers  coming  from  the  retina  –  retinoganglion  cells  –  cross  under  the  hypothalamus,  then  go  to  the  thalamus ,   then  the  Superior  Colliculus   - these  crossing  fibers  go  from  both  sides   –  forms  an  X   - just  above  the  crossing  fiber  is  the  Suprachiasmatic  nucleus   - most  fibers  go  to  thalamus  and  Colliculus,  about  1%  end  up  in  the   Suprachiasmatic  nucleus  à  important  for   entrainment     Entrainment     • entrainment  by  light,  temperature,  or  arousing  stimuli   - by  turning  on  strong  lights  =  shift  in  the  rhythm  =  you  will  get  up  earlier   - light  controls  our  clocks     - light  from  outside  environment  à  sensitive  photoreceptor  cells  (opsins)  à  opsins  à  clock  à  period   shift   - entrainment  can  easily  shift  the  period  for  2 -­‐3  hours   - if  you  want  to  shift  by  6  hours  (ex.  Jetlag)  it  will  take  2  days   - can  also  shift  hours  by  temperature  (if  its  cold  =  night,  if  its  warm  =  day)   - exercise,  sex,  or  arousing  stimulus  (anything   with  a  powerful  effect  on  the  hypothalamus  and  behaviour)  can   change  rhythms   - when  trying  to  adapt  to  jetlag,  want  to  get  to  new  cycle   - best  way  to  adapt:  change  activity  pattern  to  adapt   - stay  up  as  long  as  you  can,  exercise  in  the  afternoon  of  the  new  place ,  cycle  can  be  adapted  back  the  next   day   • photic  entrainment  in  mammals  due  to  retinohypothalamic  path  to  SCN   - entrainment  by  light  =  photic  entrainment   - occurs  by  way  of  special  opsins  in  the  retina   - retinohypothalamic  tract  carries  that  information  to  the  suprachiasmatic  nucleus   - only  1%  of  the  axons  of  the   neurons  in  the  retina  go  to  the  suprachiasmatic  nucleus   - odd  bunch  of  retinoganglion  cells   • does  not  require  rods  and  cones.  What  is  photoreceptor  in  SCN?   - Rods:  respond  to  dark  –  night  vision   - Cones:  light  and  colour  vision   - If  you  kill  the  rods  and  cones  by  a  special  lesion,  you  kill  the  entire  receptor  later   –  animals  like  hamsters   and  mice,  still  have  perfect  circadian  rhythm  with  entrainment  by  outside  light  (without  receptors)   - Th
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