1. Critical periods in development - “nature” vs. “nurture” - Part 2
Raghav Rajan
Bio 334 – Neurobiology I
September 2nd 2013
2nd September 2013
Bio Neurobiology I - Critical periods in development 2

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

3. Bio 334 - Neurobiology I - Critical periods in development 2
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
2nd September 2013
Bio Neurobiology I - Critical periods in development 2
Mark F Bear, Barry W Connors, Michael A Paradiso. Neuroscience: Exploring the brain (2007) – Chapter 23

4. Bio 334 - Neurobiology I - Critical periods in development 2
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
2nd September 2013
Bio Neurobiology I - Critical periods in development 2
Takao Hensch, Nature Reviews Neuroscience 2005

5. Bio 334 - Neurobiology I - Critical periods in development 2
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
2nd September 2013
Bio Neurobiology I - Critical periods in development 2
Levelt and Hubener. Critical period plasticity in the visual cortex. Annual Reviews in Neuroscience 2012

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

7. Increasing inhibition restores ocular dominance plasticity
Injecting diazepam (increasing inhibition) restores ocular dominance plasticity
2nd September 2013
Bio Neurobiology I - Critical periods in development 2

8. Bio 334 - Neurobiology I - Critical periods in development 2
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
Takao Hensch, Nature Reviews Neuroscience 2005
2nd September 2013
Bio Neurobiology I - Critical periods in development 2

9. 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 outgrowth
Takao Hensch, Nature Reviews Neuroscience 2005
2nd September 2013
Bio Neurobiology I - Critical periods in development 2

10. Bio 334 - Neurobiology I - Critical periods in development 2
Current understanding of ocular dominance plasticity – molecular mechanisms
Takao Hensch, Nature Reviews Neuroscience 2005
2nd September 2013
Bio Neurobiology I - Critical periods in development 2

11. 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
2nd September 2013
Bio Neurobiology I - Critical periods in development 2

12. 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!!
2nd September 2013
Bio Neurobiology I - Critical periods in development 2

13. Bio 334 - Neurobiology I - Critical periods in development 2
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 2004
2nd September 2013
Bio Neurobiology I - Critical periods in development 2

14. Broadly language learning involves perception and production
Both these aspects are affected later in life
If you can perceive sounds properly, you can produce them better – and vice versa
2nd September 2013
Bio Neurobiology I - Critical periods in development 2

15. Bio 334 - Neurobiology I - Critical periods in development 2
Only some animals are vocal learners and among them songbirds are the most experimentally tractable
2nd September 2013
Bio Neurobiology I - Critical periods in development 2

16. Early work done on the chaffinch, a common European songbird
Spectrogram 4
2nd September 2013
Bio Neurobiology I - Critical periods in development 2

17. Song learning requires sensory experience
Birds raised in auditory isolation have abnormal songs
Birds deafened early also have abnormal songs
Fernando Nottebohm. Ontogeny of bird song. Science 1970
2nd September 2013
Bio Neurobiology I - Critical periods in development 2

18. 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 1970
2nd September 2013
Bio Neurobiology I - Critical periods in development 2

19. Existence of sensitive period for song learning
Hand-raised white crowned sparrows learned from tape tutors only during days post-hatch
2nd September 2013
Bio Neurobiology I - Critical periods in development 2

20. Bio 334 - Neurobiology I - Critical periods in development 2
Some birds have only one sensitive period, while others have multiple sensitive periods
Brainard and Doupe What songbirds teach us about learning. Nature 2002
2nd September 2013
Bio Neurobiology I - Critical periods in development 2

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

22. 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
2nd September 2013
Bio Neurobiology I - Critical periods in development 2

23. Bio 334 - Neurobiology I - Critical periods in development 2
Testosterone levels, brain nuclei size and song change with breeding season
01/biol4420a/BirdPaper.Iwaniuk.Tramontin2000.pdf
2nd September 2013
Bio Neurobiology I - Critical periods in development 2

24. Neural substrates for song learning
Brainard and Doupe What songbirds teach us about learning. Nature 2002
2nd September 2013
Bio Neurobiology I - Critical periods in development 2

25. 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 added
2nd September 2013
Bio Neurobiology I - Critical periods in development 2

26. Better song learning is correlated with increased spine turnover
Lower spine turnover in adult birds that have finished learning
2nd September 2013
Bio Neurobiology I - Critical periods in development 2

27. 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
2nd September 2013
Bio Neurobiology I - Critical periods in development 2

28. Spines also get bigger after tutor song exposure
2nd September 2013
Bio Neurobiology I - Critical periods in development 2

29. Bio 334 - Neurobiology I - Critical periods in development 2
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 2013
Bio Neurobiology I - Critical periods in development 2