Critical periods in development - “nature” vs.
“nurture” - Part 2
Raghav Rajan
Bio 334 – Neurobiology I
September 2nd 2013
2nd September 2013
Bio 334 - Neurobiology I - Critical periods in development 2
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Critical periods
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How do we know it is a critical period?
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What starts the critical period?
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What closes it?
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What determines that it is closed?
–
what are the changes that can be made during the critical
period?
–
what changes cannot be made outside of the critical
period?
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Closing one eye changes representations in the visual
cortex only when done early
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Bio 334 - Neurobiology I - Critical periods in development 2
Kittens
2 days of
monocular
deprivation
Shows that
there does
exist a
critical period
3
Mark F Bear, Barry W Connors, Michael A Paradiso. Neuroscience: Exploring the brain (2007) – Chapter 23
Theoretical models predicted that the balance of
excitation and inhibition could shape column width
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First shown in
cats through
injections into
visual cortex
Agents that
reduced or
increased
inhibition
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Takao Hensch, Nature Reviews Neuroscience 2005
http://henschlab.files.wordpress.com/2012/06/hensch-nat-rev-neuro-2005.pdf
Ocular dominance plasiticity in mouse visual cortex
(without ocular dominance columns)
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Individual cells in the binocular zone can be tested for
their response to contralateral and ipsilateral visual
stimuli
Mice provide an excellent genetic system to work out the
Levelt and Hubener. Critical period plasticity in the visual cortex. Annual Reviews in Neuroscience 2012
molecular
mechanisms
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Mice knockout for GAD-65 (reduced inhibition) show no
ocular dominance plasticity
●
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GAD-65 – one of two
isoforms of an enzyme
that synthesizes GABA
– an inhibitory
neurotransmitter
No shift in ocular
dominance after
monocular deprivation
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2851625/
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Increasing inhibition restores ocular dominance
plasticity
●
Injecting diazepam
(increasing inhibition)
restores ocular
dominance plasticity
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2851625/
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Change in the amount of inhibition controls ocular
dominance plasticity
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Red circles
mark the
start, peak
and end of
normal
plasticity
Modifying
inhibition can
advance or
delay the
critical period
Takao Hensch, Nature Reviews Neuroscience 2005
http://henschlab.files.wordpress.com/2012/06/hensch-nat-rev-neuro-2005.pdf
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Synaptic changes occur after monocular deprivation
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Monocular deprivation
triggers increase in
spine motility
Spines can then be
eliminated
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Axons retract
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Spines can then recover
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Other axon outgrowth
Takao Hensch, Nature Reviews Neuroscience 2005
http://henschlab.files.wordpress.com/2012/06/hensch-nat-rev-neuro-2005.pdf
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Current understanding of ocular dominance plasticity –
molecular mechanisms
Takao Hensch, Nature Reviews Neuroscience 2005
http://henschlab.files.wordpress.com/2012/06/hensch-nat-rev-neuro-2005.pdf
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Can ocular dominance plasticity be re-induced in
adulthood
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Onset of this plasticity
determined by maturation of
inhibitory interneurons
Structural modifications are
associated with critical period
Few methods to induce ocular
dominance plasticity again
–
http://www.jneurosci.org/content/30/45/14964/F1.expansion.html
Another is to transplant
inhibitory interneuron precursors
Bio 334 - Neurobiology I - Critical
periods
in development 2
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from
donors
–
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One is to dissolve the
extracellular matrix that inhibits
axonal sprouting and growth
Facets of critical periods
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Functional competition between inputs – tunes circuits to
individual and its environment
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Structural modifications become impossible
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Regulation of onset and duration by experience, not age
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Timing is variable for different systems – one critical
period may open only when another one is done
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Inhibition plays a key role
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Attention, motivation are also very important
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Potential for reactivation in adulthood – lifelong
learning!!
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Critical periods for higher functions like language –
learning a second language as an adult is difficult
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Evidence for a critical period for language acquistion
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Socially isolated children lose ability to acquire normal
language later
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Language recovery is better after cerebral damage only if
damage occurs early in life
–
Second language learning is difficult in adulthood
Takao Hensch. Critical Period Regulation. Annual Review of Neuroscience 2004
http://henschlab.files.wordpress.com/2012/06/hensch-ann-rev-neurosci-2004.pdf
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Broadly language learning involves perception and
production
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Perception
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Production
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Both these aspects are affected later in life
–
If you can perceive sounds properly, you can produce them
better – and vice versa
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Only some animals are vocal learners and among them
songbirds are the most experimentally tractable
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Early work done on the chaffinch, a common European
songbird
http://www.birdsongs.it/songs/fringilla_coelebs/fringilla_coelebs.html# Spectrogram 4
http://en.wikipedia.org/wiki/Common_Chaffinch
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Song learning requires sensory experience
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Birds raised in auditory isolation have abnormal songs
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Birds deafened early also have abnormal songs
Fernando Nottebohm. Ontogeny of bird song. Science 1970
http://www.psy.fsu.edu/~mnl/CNL/private/Neuroeth/Nottebohm%201970.pdf
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Song learning requires intact auditory feedback
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Deafening early in
life (107 or 88d
after hatching)
results in poor
songs as adults
So, song is an
example of vocal
learning
Fernando Nottebohm. Ontogeny of bird song. Science 1970
http://www.psy.fsu.edu/~mnl/CNL/private/Neuroeth/Nottebohm%201970.pdf
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Existence of sensitive period for song learning
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Hand-raised white crowned sparrows learned from tape
tutors only during 10-50 days post-hatch
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Some birds have only one sensitive period, while
others have multiple sensitive periods
Brainard and Doupe What songbirds teach us about learning. Nature 2002
http://www.summer10.isc.uqam.ca/Page/docs/readings/WHITE_Stephanie/Brainard%20and%20Doupe%20review.pdf
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Sensitive periods are not age-dependent but instead
rely on sensory experience
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Isolated birds will learn well after their sensitive period
Birds reared in white noise conditions also have an
extended sensitive period
Castrated birds with lower testosterone also have an
extended sensitive period
In all cases, sensitive period is not extended indefinitely
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Hormones appear to be an important determinant of
sensitive periods
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Testosterone early in life for a zebra finch can
prematurely crystallize song
In open-ended learners, testosterone can trigger changes
in brain nuclei size, etc. in the breeding season
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Testosterone levels, brain nuclei size and song change
with breeding season
http://people.eku.edu/ritchisong/birdcommunication.htmlhttp://classes.uleth.ca/2010
01/biol4420a/BirdPaper.Iwaniuk.Tramontin2000.pdf
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Neural substrates for song learning
Brainard and Doupe What songbirds teach us about learning. Nature 2002
http://www.summer10.isc.uqam.ca/Page/docs/readings/WHITE_Stephanie/Brainard%20and%20Doupe%20review.pdf
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Structural modifications post first tutor song exposure
can be imaged
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Image spines on GFP
labelled neurons
Isolated juvenile birds
are tutored and spine
stability is imaged that
night
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Blue spines remain
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Yellow spines are lost
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Green spines are added
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2918377/
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Better song learning is correlated with increased spine
turnover
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Lower spine turnover in adult birds that have finished
learning
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2918377/
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Spines get stabilised within 24hrs of tutor song
exposure
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Most changes in
spine stability occur
within 48 hours of
tutor song exposure
Low spine turnover
birds learn less
High spine turnover
birds learn more
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2918377/
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Spines also get bigger after tutor song exposure
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2918377/
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Thus, overall, for sensory, motor and higher functions,
critical periods exist
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Critical periods represent periods when circuits tune
themselves to the environment and the individual
A period of “nurture” to adapt to “nature”!! (both genes
and environment)
An understanding might help facilitate life-long learning
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