STRYKER, Michael Visual Plasticity During Development UCSF May 21 2012

full title:  Competition, Active Vision and Enhanced Plasticity in Brain Development and Recovery of Function

he is from Dept of Physio, Center for Integrative Neurosci at UCSF = UC San Francisco.

lecture is at 5:15 PM  Monday May 21 2012 in Clark Bldg , S361. at Stanford (an MBC hosted lecture).

slide 1 = sl:
development of V1... occurs in stages...

in mouse... same course of development in monkey and human and ferret...

weeks 1-2 (post-natal)  topogr map formation and refinement:  formation of orderly connections btwn areas
this sequence is mainly in mice...  mice open their eyes for the first time around day 12.
photoreceptors and RGCs = retinal ganglion cells are wiring together during this period, also.

weeks  2-3  elab of highly specific receptive fields...   (eyes only open AFTER  topographic  map formation)

(note  rgc = retina gangl cells  are NOT connected to photoreceptors initially...  but there is spontan activity)

weeks 2-3  select for  oriented edges...  must have topography first, obviously  before u can get oriented edges.

weeks 4-5:  4th week post-natal in cats also  (this is in mouse)...  ocular dominance plasticity and the
MATCHING of recep fields of  the two eyes.

before this...  cells from L and R eyes  have DIFFT  recep fields...  
visual experience is crucial to MATCH recep fields
btwn the 2 eyes...  after this period  they are MATCHED perfectly...

(note: can have  visual stimulation that is NOT experience-dependent, eg from waves of retinal depolarization,
which occur early)

thereafter...  adult...

MD = monocular deprivation of an eye...

he shows alternating  dominance in V1  in layer IV (ocular dominance columns)

he shows cat data after MD...  there is rapid loss of ability to drive coritcal cells  in 1-2 days  even before  atrophy of dendritic tree of cells...
(initl, most cells can be driven by either  R or L field.. but after MD, lose that within 1-2 days... so, what is the mechanism?)

thot that  cells were competitng for neurotrophins... but hard to know...

he studied retino-genic-cortic  pathway in  MOUSE

there is rapid activity dependent plasticity in V1  (shown by Josh Gordon in 1996)  

usually at this point, people start to hum...Three Blind Mice.... 
 (mouse don't see; they have big whiskers..  but actually not true, they DO see
and their anatomy resembles large mammals)

Niell and Stryker  2008...  used silicon trodes for  multi site vertical recording fron multiple layers within a single penetration
 (vertical array...can record from both inhib and excit cells..

sl:   mouse recep fields are as pretty and distinct as those in cats... a la Hubel and Wiesel.

correspond to simple and complex cells of H and W.

recep fields in Mouse are similar to Cat and Monkey...

Most neurons are responsive as simple cells...

****

Kaneko Nat Neurosci in 2008

showed  need for TrkB for recovery  (it turns on neurotrophin signalling)... pronounced Track-B.

perhaps neurons can turn up their gain  (homeostatically)  as a means for explaining
earlier changes  (before recovery)

Rob Malenka lab...  showed importance of glial TNF (tumor necrosis factor) alpha... seems that its requried for
homeostatic synaptic scaling...

(eg,  incr in  response of  ipsilateral eye (open eye) during the time of MD of contralat eye.)

this is a cortical phenomenon  (not a peripheral phenom)

just depends on the level of activity  (if you're not driving the cell by the contralat eye, then
it turns up its response to compensate for loss of input)

Summary:
change of response (after  2-3 days) is due to loss of synapses in closed-eye circuit...

recovery appears to be due to  re-growth of synapses...

but all these measurements were in anesthetized animals... and anesthesia is an important
modulating factor... if anesthesia is deep enough, you can really suppress spiking... so,
ideally, you'd like to do expts in awake animals...

(but u get plasticity when the animals are walking around!  not when  anesthetized....

so,  they used the same prep that
David Tank lab developed...  mice walking on a beach ball  of styrofoam   that turns  (its floating on air)
as the mouse walks on it  (a round mouse-style treadmill) in whcih the mouse remains stationary despite walking,
so that neural activity may be recorded.

see Niell and Stryker  in Neuron in 2012...

mouse was always alert and attentive during treadmill walking...  (he shows a great video clip)

visual responses (spiking in V1 neurons)  were much larger when walking than when stationary...

(only in V1  not in LGN)

somehow u turn up the gain in the mouse when its  walking...

visual cortex gain gets turned up by walking

do calcium imaging in awake mouse ... htis confirms incr reponse with locomotion

(same thing occurs in fruit flies)

what is the mechansim of this?

great video....  blue light is on and mouse starts to run...
blue light modulates cortical activity...  they use

optogenetic stim by ChRhodopsin2)

would these enhanced responses result in incr plasticity in adult visual cortex? 
 eg due to... enriched enviros,  etc... (a la Marion Diamond)

give mice 4 hours per day...  of  visual stim + running on ball  (when recovering from 150 days of MD)

they recover  more in 1 week than control does during its entire lifetime...
simultan visual stim  + locomotion  really prompoted recovery in adult brain
during recovery from   MD = mono depriv.

used moving gratings  as visual stim...
but note:  the visual recovery is  very specific  (either to  visual noise or to moving bars)
if u see moving bars... that's what recovers
if u see noise, then that's what recovers...  !!!!   (ie recovery is specifically turned to the stim that
the mouse sees during recovery)

this was Kaneko work in PNAS...

Sebastian Espinoa in 2011 (unpub) is actually looking at synapses (looking at psd95-gfp)
and also looking  at synaptophysin  (same markers that Stephen Smith's guys use)

much better to look at  psd95 than at photos of  spine growth 
(cuz  confocal microscopy is not constant over time but concentration of psd95 is steady over time...
ie  more accurate measurements by using immunofluor tech. than by staring at spines using confocal microsc.)...

he is looking at  psd95-gfp puncta in single excitatory neurons in layer 3...  

structural correlate of post-synapt scaling  (that is assoc with recovery) is  regrowth of synapses...

loss of connections and regrowth of connections...  dramatically modulated by  neural activity (in adults)...
(same message that Mike Merzenich emphasizes... use it or lose it)

*****

bw = brian wandell:  comments on work that he recently heard from donald mitchell's lab:
  absol darkness is another way of inducing changes in mice  darkness  
bw  quotes  donald mitchell work

MS comment: depends on  bdnf  synthes actually IN the dendrites...

bw  asks abt ambliopes  who run/ jog... do they do better?  ... hard to know...

after 2-3 days of MD  do NOT get any change in layer 4 of V1  (only see changes in Layer 2/3...
Michael Silver looked for years and could not find early changes in thalamocortical system after MD within 2-3 days...
only after 6 days.

(Michael Merzenich is more optimistic abt recovery after LT deprivation than MS but
MS  = Stryker is NOT  . (recovery is never complete)

we chat afterward with Jay McC.

espec interesting:  so  are visual pathways structured by nature or nurture?
A:  combo...  
MS emphasizes... can have NON-experience dependent patterning of visual pathways that is nonethless ACTIVITY-dependent...
that is, its due to spiking (eg RGC spiking) that is NOT-exper. dependent... eg  with eyes still closed during first 2 weeks after birth.