Modification of Brain Circuits as a Result of Experience – Chapter 24, Purves et al. 4th Ed.

Pre-natal construction of neural circuits (the “highways” are genetically specified):

(1/6/2010) – Mona Buhusi

Postnatal modification of neural circuits (e.g., learn a language):

Adapt to changing external environments, changes in head & brain size

Temporal windows for the brain to become refractory to the lessons of experience – critical or sensitive periods, e.g. learning a new language

Neural activity triggers the refinement of connections via calcium, neurotrophins, local gene expression, cytoskeleton

Postnatal Experience =

patterns of neural activity

System, circuit, or cell waiting for specific instructional information from the environment in order to continue to develop…

… If “appropriate” experience is not gained during the critical period, the pathway may never attain the ability to process certain forms of information, e.g. depth, and perception may be impaired permanently.”

During a critical period, the system can adapt to virtually any stimuli, appropriate or inappropriate.

It is possible to delay/accelerate the critical period, e.g. environment – dark rearing; molecules – GABA

Idea of a critical period

Box 24A Built-In Behaviors: Experience is an ON switch

Goslings forever follow the first large moving object they hear and see during their first day of life.

This imprinting is irreversible.

Vision and audition are very poorly developed in newborn mammals – rely more on olfaction.

Olfaction – more evolutionary primitive…

1)  Duration is proportional to lifespan

2)  Functional competition between inputs (e.g., left vs. right eye)

3)  Neuronal activity (action potentials, forward and back propagating)

4)  Structural consolidation of pathways

5)  Onset and duration is defined by neural activity

6)  Different critical periods for different systems: e.g., direction selectivity and ocular dominance are plastic at

different times

6) Diversity of sensory/motor systems & molecular mechanisms

7) Particular roles of excitation and inhibition – GABA can open the critical period

8)  Potential for reactivation? (training, growth factors)

Autism, Schizophrenia: critical period disorders?

Properties of critical periods

Figure 24.1 Manual “babbling” of hands in deaf versus hearing infants

(Pre

curs

ors f

or si

gn-la

ngua

ge)

Figure 24.2 Learning language

Box 24B Birdsong

Listen to adult male tutor 10-20 times

Successful courtship depends on early auditory and vocal experience

• Lyre bird - Australia

http://www.youtube.com/watch?v=VjE0Kdfos4Y

Use it or lose it or more sophisticated?

Visual system:

Much clearer understanding of how changes in connectivity contribute to critical periods:

Infinite control and reproducibility of visual stimuli in space and time.

Visual cortex (not retina or thalamus) is especially plastic.

Figure 12.8 Neurons in the primary visual cortex respond selectively to oriented edges

Contrast invariance of orientation tuning

Figure 12.11 The basis of functional maps in primary visual cortex (Part 1)

Figure 12.11 The basis of functional maps in primary visual cortex (Part 2)

Figure 12.12 Functional imaging techniques reveal the orderly mapping of orientation preference in primary visual cortex

Anatomy and physiology of ocular dominance plasticity

Axons from cells in the lateral geniculate nucleus (LGN) serving each eye terminate in separate bands in layer 4 called “ocular dominance columns”.

Ocular dominance maps superimposed on orientation maps – spatial scales are different

Visual cortex

Layer 4

Layer 2/3

Figure 12.13 Mixing of the pathways from the two eyes first occurs in the striate cortex

Human visual cortex: Ocular dominance columns

Box 24C Transneuronal Labeling in animals using Radioactive Amino Acids

Could be problematic in early development if …?

Figure 24.3 Ocular dominance columns in the primary visual cortex of an adult macaque monkey

Technique could be problematic in early development if …?

How can one label ocular dominance columns in the human brain?

Autoradiographic montage showing the ocular dominance columns in layer 4c of the left striate cortex of a macaque labeled by injection of radioactive proline into the left eye.

Cytochrome Oxidase (CO) montage prepared from alternate sections showing the ocular dominance columns revealed by enucleation of the right eye. CO and [3H]proline are identical.

Cytochrome Oxidase – mitochondrial (metabolic) enzyme

Human

3,477 mm2

Macaque

1,127 mm2

Right occipital lobe from a 79-year-old man blind for one year in his left eye.

Half-way through dissection process

Human visual cortex continued

Complete flatmount prior to microtoming

Human visual cortex continued

Complete Pattern of Human Ocular Dominance Columns

Human visual cortex continued

Columns after applying a Fourier filter and a threshold function

Human visual cortex continued

Human visual cortex continued – fMRI of ocular dominance columns

Development of Ocular Dominance Columns, as identified by transneuronal labeling

Do LGN inputs in visual cortex normally undergo developmental segregation…?

LeVay, Stryker, Shatz, 1978

Ocular dominance columns in cat visual cortex

Could be problematic in early development if …?

Figure 24.6 Effect of monocular deprivation on ocular dominance columns in the macaque monkey

Normal Monocularly deprived after birth

Deprived eye columns are shrunken, not disappeared. So not disuse mediated withering away but competitive imbalance

• We are born with ocular dominance columns but abnormal experience can modify them.

• Depth (stereo) vision develops 4-6 months after birth in humans.

Figure 24.7 Effect of monocular deprivation on terminal arborizations of lateral geniculate nucleus axons in the visual cortex – Cat area 17

(1 week)

Effect of monocular deprivation on terminal arborizations of lateral geniculate nucleus axons in the visual cortex – Cat area 18

Potential for recovery?

Physiology of ocular dominance: Record the response to left vs. right eye stimulation independently

Figure 24.4 Effect of monocular deprivation on ocular dominance in kittens v. adult cats (Part 1)

Figure 24.4 Effect of monocular deprivation on ocular dominance in kittens v. adult cats (Part 2)

Disuse or Competition?

Deprived eye disconnected?

Figure 24.5 Effect of short period of monocular deprivation at height of critical period in cat

Disuse or Competition?

(need to do another exp – binocular deprivation)

Deprived eye disconnected?

Hubel & Wiesel’s work directly impacted how human babies are treated after monocular eye injuries or if they are born with a cataract

Figure 24.9 Ocular dominance in adult cats in which strabismus was induced during critical period

Hubel & Wiesel’s work directly impacted how human babies born with squint are treated

Overall activity is the same for both eyes, but correlation from corresponding retinal points is different

Figure 24.4 Effect of monocular deprivation on ocular dominance in kittens v. adult cats (Part 3)

Binocular deprivation: Disuse does not induce ocular dominance plasticity.

Competition and local correlations in neural activity (spikes) are the drivers of plasticity

Figure 24.8 How Hebb’s postulate might operate during development of the visual system

cooperate

compete

Post- matches Pre-

Box 24D Correlation as Causation: Lessons from a Three-Eyed Frog

“Gain of function”

Figure 24.10 Transduction of electrical activity into cellular change via Ca2+ signaling

Change dendrite/ spine structure

Molyneux's problem is an unsolved problem in philosophy for more than three centuries:

“If a man born blind can feel the differences between shapes such as spheres and cubes, could he similarly distinguish those objects by sight if given the ability to see?”

Can one begin to have sight late in life, past the critical period? If so, can such subjects provide insight into how we learn to see?

One in 100 children in India is blind, largely from congenital cataracts that go untreated. In the US & Europe, cataracts are an disease of the elderly. Limited care due to cost and limited hope due to “apparent” dogmas.

What if a “blind” adolescent or adult (born with congenital cataract) receives surgery (as adolescents or adults), what would they see?

Note that a congenital cataract does result in some form vision and motion sensitivity intact, its just that acuity is gone.

Initially in these patients that receive new lenses, there are integrative difficulties – meaning that they see fragmented pieces rather than whole/singular objects (like autism).

But motion cues can help parse objects from background or one overlapping object from another. After a few weeks or months of experience, motion is no longer required to parse objects.

Motion cues and thus motion-sensitive neurons in the primary visual cortex is a likely bootstrap for visual learning and developing integrative skills.

Does the recovery of object recognition in “lens blind” subjects challenge Hubel & Wiesel’s findings on ocular dominance plasticity?