2nd september 2013bio 334 - neurobiology i - critical periods in development 21 critical periods in...

2nd September 2013 Bio 334 - Neurobiology I - Critical periods in development 2 1

Critical periods in development - “nature” vs. “nurture” - Part 2

Raghav RajanBio 334 – Neurobiology I

September 2nd 2013


Critical periods

● How do we know it is a critical period?● What starts the critical period?● What closes it?● 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?


Closing one eye changes representations in the visual cortex only when done early

● Kittens● 2 days of

monocular deprivation

● Shows that there does exist a critical period

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● First shown in

cats through injections into visual cortex

● Agents that reduced or increased inhibition

Takao Hensch, Nature Reviews Neuroscience 2005http://henschlab.files.wordpress.com/2012/06/hensch-nat-rev-neuro-2005.pdf


Ocular dominance plasiticity in mouse visual cortex (without ocular dominance columns)

● 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 molecular mechanisms

Levelt and Hubener. Critical period plasticity in the visual cortex. Annual Reviews in Neuroscience 2012


Mice knockout for GAD-65 (reduced inhibition) show no ocular dominance plasticity

● 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/


Increasing inhibition restores ocular dominance plasticity

● Injecting diazepam (increasing inhibition) restores ocular dominance plasticity



Change in the amount of inhibition controls ocular dominance plasticity

● Red circles mark the start, peak and end of normal plasticity

● Modifying inhibition can advance or delay the critical period



Synaptic changes occur after monocular deprivation

● Monocular deprivation triggers increase in spine motility

● Spines can then be eliminated

● Axons retract● Spines can then

recover● Other axon

outgrowthTakao Hensch, Nature Reviews Neuroscience 2005http://henschlab.files.wordpress.com/2012/06/hensch-nat-rev-neuro-2005.pdf


Current understanding of ocular dominance plasticity – molecular mechanisms



Can ocular dominance plasticity be re-induced in adulthood

● 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

– One is to dissolve the extracellular matrix that inhibits axonal sprouting and growth

– Another is to transplant inhibitory interneuron precursors from donors

http://www.jneurosci.org/content/30/45/14964/F1.expansion.html


Facets of critical periods

● Functional competition between inputs – tunes circuits to individual and its environment

● Structural modifications become impossible● Regulation of onset and duration by experience, not

age● Timing is variable for different systems – one critical

period may open only when another one is done● Inhibition plays a key role● Attention, motivation are also very important● Potential for reactivation in adulthood – lifelong

learning!!


Critical periods for higher functions like language – learning a second language as an adult is

difficult● Evidence for a critical period for language

acquistion

– Socially isolated children lose ability to acquire normal language later

– 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 2004http://henschlab.files.wordpress.com/2012/06/hensch-ann-rev-neurosci-2004.pdf


Broadly language learning involves perception and production

● Perception● Production

● Both these aspects are affected later in life

– If you can perceive sounds properly, you can produce them better – and vice versa


Only some animals are vocal learners and among them songbirds are the most

experimentally tractable


Early work done on the chaffinch, a common European songbird

http://www.birdsongs.it/songs/fringilla_coelebs/fringilla_coelebs.html# Spectrogram 4http://en.wikipedia.org/wiki/Common_Chaffinch

http://www.birdsongs.it/songs/fringilla_coelebs/fringilla_coelebs.html


Song learning requires sensory experience

● Birds raised in auditory isolation have abnormal songs

● Birds deafened early also have abnormal songsFernando Nottebohm. Ontogeny of bird song. Science 1970http://www.psy.fsu.edu/~mnl/CNL/private/Neuroeth/Nottebohm%201970.pdf


Song learning requires intact auditory feedback

● 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 1970http://www.psy.fsu.edu/~mnl/CNL/private/Neuroeth/Nottebohm%201970.pdf


Existence of sensitive period for song learning

● Hand-raised white crowned sparrows learned from tape tutors only during 10-50 days post-hatch


Some birds have only one sensitive period, while others have multiple sensitive periods

Brainard and Doupe What songbirds teach us about learning. Nature 2002http://www.summer10.isc.uqam.ca/Page/docs/readings/WHITE_Stephanie/Brainard%20and%20Doupe%20review.pdf


Sensitive periods are not age-dependent but instead rely on sensory experience

● 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


Hormones appear to be an important determinant of sensitive periods

● 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


Testosterone levels, brain nuclei size and song change with breeding season

http://people.eku.edu/ritchisong/birdcommunication.htmlhttp://classes.uleth.ca/201001/biol4420a/BirdPaper.Iwaniuk.Tramontin2000.pdf

http://classes.uleth.ca/201001/biol4420a/BirdPaper.Iwaniuk.Tramontin2000.pdf


Neural substrates for song learning

Brainard and Doupe What songbirds teach us about learning. Nature 2002http://www.summer10.isc.uqam.ca/Page/docs/readings/WHITE_Stephanie/Brainard%20and%20Doupe%20review.pdf


Structural modifications post first tutor song exposure can be imaged

● Image spines on GFP labelled neurons

● Isolated juvenile birds are tutored and spine stability is imaged that night

● Blue spines remain● Yellow spines are lost● Green spines are

addedhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2918377/


Better song learning is correlated with increased spine turnover

● Lower spine turnover in adult birds that have finished learning



Spines get stabilised within 24hrs of tutor song exposure

● 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



Spines also get bigger after tutor song exposure



Thus, overall, for sensory, motor and higher functions, critical periods exist

● 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

2nd september 2013bio 334 - neurobiology i - critical periods in development 21 critical periods in...

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