Critical Periods and Plasticity

Critical Period for Flial Imprinting

Heinroth, 1911; ducklings vs. goslings

Konrad Lorenz, 1970; critical period for imprintingCritical period for parental

imprinting in ducklings

Harry Harlow, 1950sSurrogate mother experiments

Critical Period for Attachment

Stoeckel et al., 2005, J Neurophysiology

Thalidomide toxicity during 1st trimester.

Critical Period for Prenatal Toxicity onLimb Development

Critical Period for..Language acquisition: 6 months (onset)

Phoneme selectivity: 6 months (end)

Critical Period for Language Acquisition

Kuhl, 2004

http://psych.rice.edu/mmtbn/language/sPerception/infantsucking_h.html

http://www.tau.ac.il/~tsurxx/ba_da_ga.mp3

Do American infants hear Swedish vowels?

Language Acquisition

Development of languageis independent of the modeof expression.

Language Acquisition

Critical Period for Acquisition of Second Language w/o anaccent: 7-8 years

Critical Period for Song Acquisition

Critical periodends at puberty

Selectivity for songs ofown species.

In the lack of ownspecies’ song….adaptation.

…imprinting in the chick…brain sexual differentiation…extraocular muscle development…visual plasticity…monocular deprivation…addiction vulnerability…wing pattern induction in the polyphenic tropical

butterfly…GABAergic receptor blockade for induction of a cAMP-

mediated long-term depression at CA3-CA1synapses

…methamphetamine-induced spatial deficits…second-language acquisition…experience-dependent Plasticity in Visual Connections

in Xenopus…lung cancer susceptibility…cross-modal plasticity in blind humans…nicotine exposure effects…disruption of primary auditory cortex by synchronous

auditory inputs…functional vestibular development in zebrafish…right hemisphere recruitment in American Sign

Language processing…barrel cortex critical period plasticity…feminization in tilapia…developmental climbing fibre plasticity…sensory map plasticity…sensitivity to juvenile hormone…language acquisition…LTP at thalamocortical synapses…caste determination in Bombus terrestris and its

juvenile hormone correlates…deafferentation-induced apoptosis

…nicotine-induced disruption of synapticdevelopment in rat auditory cortex

…activity-dependent synapse elimination indeveloping cerebellum

…conversion of ectodermal cells to a neural crestfate

…psychosis…verbal language development…reduced brain vulnerability to injury.…chorda tympani nerve terminal field development…the sensitivity of basal forebrain cholinergic

neurones to NGF deprivation…light-induced phase advances of the circadian

locomotor activity rhythm in goldenhamsters

…the influence of peripheral targets on the centralprojections of developing sensory neurons

…the specification of motor pools in the chicklumbosacral spinal cord

…axon regrowth through a lesion in the developingmammalian retina

…long-term potentiation in primary sensory cortex…song learning in the zebra finch…restoration of normal stereoacuity in acute-onset

comitant esotropia…transcription for induction of a late phase of LTP.…regeneration capability of adult rat retinal

ganglion cells after axotomy..synaptogenesis..experience-dependent synaptic plasticity in rat

barrel cortex..peripheral specification of dorsal root ganglion

neurons..androgenic block of neuromuscular synapse

eliminationspeech lateralization in deaf populations

Critical period for ……

What is a critical period?

“During a critical period, a pathway awaitsspecific instructional information in order to continuedevelop normally. … If appropriate experience is notgained during the critical period, the pathway neverattains the ability to process information in a normalfashion and, as a result, perception or behavior isimpaired permanently.”

Alternatively……

“During a critical period, a pathway maintains astate of vulnerability to unusual stimuli. …. If aninappropriate experience is maintained during thecritical period, the pathway sustains adaptive changespermanently.”

Critical period for stereopsis… in humans

Unbalanced binocular stimulation during a critical perioddisrupts normal vision.

Neonatal unilateral cataractCorrections.. before 4 months: minimal visual loss…between 6-30 months: finger counting acuityCataract forming after 3 years: responsive to correction

Strabismus: Correction after 1 years: loss of stereopsisCorrection after 4 years:

strabismic amblyopia

Visualization of ocular dominance columns

Critical period for stereopsis … in monkey

Effect of Visual Deprivation on Ocular Dominance Columns

Visual cortex ofnormal adultmonkey

18 months old.MD at 2 weeks. Labelinjected intonondeprived eye.

Autoradiographs from visual cortex, 10 days after tracer injected into one eye

18 months old.MD at 2 weeks. Labelinjected into deprivedeye.

Hubel, Weisel and LeVay, 1977

Horton and Hocking, 1999

Lid sutured when 1 week old. Lid sutured when 7 weeks old.

Critical period (window ofopportunity for successfulsurgery): postnatal weeks 1-5.

Normal

Deprivation leads to shrinkage of deprived axons, followed by expansionof non-deprived axons.

What explains the shrinkage of columns?

Do the anatomical changes affect the physiology?

More cells in cortex become monocular

How about a shortterm deprivation(which shrinks thedeprived axons butdoes not expand thenondeprived axons)?

Can this be just an outcome of reducedactivity from one eye?

No. Monocular deprivation inthe adult does not changethe physiology or theanatomy.

Does visual activity have anything to do with it?

Yes. When the visual activity is totally prevented bykeeping the animals in complete darkness, criticalperiod for plasticity is delayed.

Visual activity is necessary to open the criticalperiod.

Determining the critical period

1) Do you have an assay for plasticity or stability?

e.g. MD changes ODC wiring.

2) Close one eye for a given duration

e.g. 2-7 days of MD is sufficient to induce ODchanges

3) At suture removal day, asses OD.

Onset of critical period: The youngest age atwhich initiation of MD leads to at least 50% oculardominance shift.

End of critical period: Oldest age at whichinitiation of MD leads OD shift.

Determining the critical period

Issa et al., 1999, JNeurosci.

Finding #1: Oculardominance columnssegregate by 5-6 weeks inthe cat.

Finding #2: Critical periodof plasticity in cats end by 6weeks.

Then: critical period endswhen the columnssegregate.

So, what makes geniculo-cortical axons vulnerableto deprivation?

Model 1: Deprivation stops a normal developmentalprocess.

LeVay, Stryker, Shatz, 1978

Katz and Shatz

Hebbian Mechanisms for development

Beautiful model. But,…... the data do not validate the predictions.

Model #2: ocular dominance column formation andcritical period plasticity are independent events.

Evidence #1: ODC develop earlier then the onset ofcritical period

Monkey at birth Ferret at P18CP:P32-P60

Cat at P14CP:P21-P40

Evidence #2: Dark-rearing delays the criticalperiod, but not ODC segregation.

monocularenucleation

Fine. Then, what does enable the plasticity of thebrain during a critical period?

Why do deprived axons retract?

Active synapses hold onto their targets (remember NMJ?).

Why do nondeprived axons bother to invade theterritory? And, how do they know about what ishappening to the deprived axons?

What prevents or facilitates plasticity of the brainduring a critical period?

Factors that may be involved in Critical Period Plasticity:

* NMDAR* metabotropic glutamate receptors

PKC activation* CaMKinase* BDNF

prevents MD effectsprevents DR effects

* GABAergic activity* ACh/NE* Hormones

Properties of critical periods:1) Functional competition between inputs2) Neuronal activity3) Structural consolidation of pathways4) Onset and duration is defined by

activity5) Sequence of critical periods across

systems6) Diversity of molecular mechanisms7) Particular roles of excitation and

inhibition8) Attention and motivation9) Potential for reactivation

Properties of critical periods:

1) Functional competition between inputsBinocular lid suture ==> no OD shiftActivity blockade in cortex during MD ==>

nondeprived axons shrink!

Hata, Tsumato,

Stryker, 1999

Nondeprived

Deprived

2) Neuronal ActivityDark-rearing ==> Critical period delayed

3) Structural consolidation of pathways

Plasticity may persist in some pathwaysthroughout development. But, not in others…

4) Onset and duration is defined by activityDark rearing, enriched environments, BDNF..

5) Sequence of critical periods across systems

barrel ctx plasticity…. Visual cortexplasticity

Layer 4 CP … layer 2/3 critical period

6) Diversity of molecular mechanismsTC to layer 4 plasticityLayer 4 to layer 2/3 plasticityocular dominance vs orientation column

plasticity

7) Inhibition is important.

Result: When GABA is reduced, CP doesn’t start.When GABA is replaced, CP starts.

Conclusion: GABA is necessary for initiation of CP.

Enhancementof GABAergicactivityinitiate CP.

MD shifts OD responses

Restoration of MD, restoresOD

Short MD

OD is restored even afterMD into post CP ages

Long MD

But not if MD is initiatedbefore eye opening.

Early-Long MD