Overview of neuronal development

Neuronal survival vs. apoptosis

Competition for cortical space

The critical period

Cortical plasticity in the adult

Early experience and neural development

Neuronal Development

Growth and Differentiation of the Vertebrate Brain

CNS begins to form at two weeks gestation

At birth, brain weighs 350g, at one year 1,000g

Growth and Development of Neurons

Proliferation- production of new cells

Migration- move toward final destination

Differentiation- form axons and dendritesDiverse shapes of neuronsTransplantation experiments

Myelination- addition of insulating sheath

Neuronal survival

At 11 weeks (gestational age) we have 2-3 times as many neurons as needed

“Pruning”: As connections are formed the number drops (until 25 weeks)

What determines which neurons survive?Studies by Hamburger, Levi-Montalcini

Neuronal survival

What determines which neurons survive?Studies by Hamburger, Levi-Montalcini

Competition for “trophic factor” secreted by targetexamples: NGF, BDNF, GDNF; (specific receptors on neurons)

Winners survive, losers undergo “apoptosis” (programmed cell death)

Who wins competition for connections/ trophic factors?

- Activity dependent development of primary visual cortex (V1): Ocular Dominance Columns (ODC)

Visual system: partly crossed in human, monkey, cat

Each half of V1 receives input from both eyes

Some V1 cells respond to only one eye, some to both

Cells with similar ocular dominance are organized in columns

Changing the balance of activity between the two eyes:

Effects of Monocular Deprivation- early vs. late deprivation; “critical period”

Binocular deprivation birth to 3 months (monkey)

Observations in Frog Visual System

Questions:

1. How would you demonstrate involvement of trophic factor?

2. What implication do the findings have for the removal of congenital cataract? (video clip)

Conclusions

Neuronal survival is mediated by competition for target-derived trophic factors.

Similarly, cortical organization is mediated by activity-dependent competition early in life (i.e. during the critical period).

This activity-dependent competition appears to be mediated by trophic factors.

Normal experience during the critical period that leads to normal neural activity is essential for normal cortical development.

How drastically can cortical organization be influenced by sensory inputs?

- auditory cortex responds to vision in “rewired” ferret brains (von Melchner et al., 2000)

- visual cortex in the congenitally blind is responsive to touch

Plasticity later in life

Cortical reorganization in somatosensory cortex:

- monkey amputation studies- phantom limbs- string players- effects of non-use in stroke patients

Phantom Limb Sensations:

Sensations in amputated handarise when face is touched.

Explanation:Axons from face now activatehand area in cortex.

Since neurons in cortex hand area represent feelings in hand, their activity is experienced as arising from non-existent hand!