Jessel, Thomas - Columbia
<p>May 14, 2010 9:54 AM
 
English;  PhD  Cambridge.  Royal Society of London;  Inst of Med;  For Assoc of NAS.
Kavli Prize in Neuroso.
 
HHMI Investigator and at Columbia since 1985.
 
*
Talk was in  Hewlitt TC  201 from 4:15 to 5:30P  on May 13.
 
 
Eric Knudsen  introduced by Eric Shooter Lectureship.
Eric Knudsen did the work on barn owl  sound localization.
 
 
 Jessell gave the Eric Shooter Lecture.  Eric discov  nerve growth factor.
Eric Shooter founhded the neurobio Dept at Stfd in 1973.
known for his collegiality.
 
Jessell was an asst prof at Columbia since 1981.
 
founded Ontogeny.   he was introduced by Ben Barass  (glial cell guy)  who
was a grad student at Hvd when Tom J was an aasst prof there.  27 yrs ago.
 
HIS KEY SUBJECT in NEURONS and NETWORKS for SPINAL MOTOR CONTROL
(eg  WALKING in cats).
 
PLANNING of motion is  obv  supraspinal ...  cortex and cerebellar;
 
EXECUTION has a heavy spinal component (espec in lower animals)
Sherrington on, havev been inter.
 
All of these spinal reflexes rely on MN's  motor neurons to  initiate the patterns ...
eg  grasping, locomotion.
 
there are 600 muscles in the human body.
 
Extensors and Flexors  are antagonist pairs...  when one fires, the other is silect
 
his favorite pair  is  gastroc  (GI)  vs  TA  (tibialis anterior) ... walking muscles in rats , I guess.
 
Extensors have these  5 sec  bursts  alternating with 1 sec burst in flexors.
 
both are  involved in  stretch reflex closed loops starting with
DORSLA SENSORY neurons  (either  proprioceptive or  tendon reflexes)
 
can be either  monosynaptic  (fat reponse)  or  incorporate
an  interneuron  (slower)  to modulate  and pattern response.
 
Problem  1:  in  early development,  how do the pools of MN's  form which
innervate individual muscles like the GI or the TA.  (they are all located together
in the ventral horn.  ie how do   neuron pools and their muscle targets associate.
 
 
each limb has  75 muscles.  he shows an example slide with the tib anter  neurons altogether
relatv  dorsally  relative to the tensor fascia lata and glut. medius.
 
So,  how do these cells acquire their identity???
 
There are two  key dimensions:  DV  (dorsoventral) and  AP  (he calls it anter poster)
but my seatmate clarifies this... he really means  rostral causal  (remember these are
creatures on all fours).
 
There are gradients of chemicals that  give them their identities.
 
Shh is  Sonic Hedgehog...  cord picks up  transcription  factor sensitivity
?  from Shh.  their are gradient sof  transcription factors.
 
forelimb is developed by  HOX6  vs  torso  by  HOX9.
 
these factors mutually inhibit one another, so there is a predominance.
 
HOX genes ASSIGN  the  transcriptional  identity to pools of MN's.
 
Experiemtn to test this...  TURNB OFF  HOX6  by using  RNAi to reassign identity.
 
There are  21  motor neuron (MN)  HOX proteins.
 
Jeremy  (one of his people now his own lab)  showed that
FOXP1  is only expressed in forelimb  NNs.
 
So,,  HOX  turns on  FoxP1  which turns on identitiy of columnar pools of MN's.
 
Test this  (experiemnt)  :  get a floxed  FoxP1 mouse to selectively toggle it.
 
when u turn off FoxP1  get a mouse  that moves like a lamprey or hagfish...
uses limbs  like flippers in a seal,  pathetic video.   profound defect.  relative to
WT  (= wild type).
 
turning off  FoxP1  destroys the  coordiantion (anticorrelation) of antagonist muscles
like  GI and TA ...  they both fire together instead of alternatiing.
 
 
 
Wild type has nice  anticorrelated firing of neurons  (mediating walking)
FoxP1  vaqriant  has scattered firing  (salt and pepper mixture instead of
isolated  MN pools corresp to  TA and GI)  so they fire together all the time... pathetic.
u get erosion of pool identity when  FoxP1 is turned off.
 
An aside...  gap junction  firing is important in  clustering the MNs also.
 
Now,  what determines  the LOCATION of  the various clusters of MNs...
Answer is  the location of the  ends of the axons of the sensory neurons  (their soma is
in the DRG  dorsal root gang.)
 
He calls this ZONAL TARGETING
 
On a cross section of spinal cord  shosing the ventral horm,
 
distal  musculature (eg  fingers, toes)   MN pools are located  relatively dorsally  and
proxial  (triceps, gluteus)  are  relativ  ventgral.
 
Next prob.  what determines whether  a  relfex  is monosynaptic  eg  from spindle cells
eg  triceps  is monosynaptic  v  fast  2 msec latency  
VS  INDIRECT... (incorporating interneurons...  eg  from golgi  endon  1B cells.
 
Answer:  sem3e  REPEALS  afferents  from  sensory neurons .
 
Absence of  sem3e  allows  monosynaptic  loops to form  cuz then the
axonal buotons  from the  DRG cells  can synapse directly to
the MNs.  he pronounces it  BOO  tons.
 
WT  wild type  has  sem3e  and they repel  bootns.
 
*
Summary:
 
Zonal targeting is by  dorsal axons  (from  DRG cells)
Mono vs  polysynaptic  is by  sem3e.
 
pool  specifiicty if by  HOX genes...  to determin  ID of a partic  pool of MNs
witha partic muscle.
 
*
New topic:  INTERNEURONAL CIRCUITS fro Limb Movement.
 
Motor  Neurons get  50,000  inputs !!!!!
 
he looks at large  cholinergic  boutons.
where do they come from?
 
Each  DRG  may make  2,000  synapses.
 
interneurons are phase locked  witht he motor output.
 
He mentions  CPG  central pattern generator.
 
 
 
 
 
 
 
 
 
 
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