Neurodevelopment & Neuronal Plasticity

Stages of Brain Development

1. Cell birth/proliferation

2. Cell migration

3. Cell differentiation and maturation

4. Synaptogenesis and synaptic pruning

5. Cell death

6. Myelination

1. Cell Birth/Proliferation

• neurogenesis does not take place within neuronal division

• stem cells divide to form progenitor cells

• can be either neuroblast or glioblast

• neural tube gives rise to the ventricular system in a mature brain

2. Cell Migration

• movement of newly formed cells towards outer layers

• cortex develops in inside-out manner

• occurs with help of: chemical signals (e.g. immunoglobulins) and physical support (e.g. cells ‘ climb’ radial glia)

• a large wave of neurons still migrate in frontal cortex after birth

3. Differentiation and Maturation

• once at destination, immature neurons begin to express particular genes allowing them to become particular type of cell

• they start to from axon and dendrites

• dendritic development: dendritic arborization (branching), and growth of dendritic spines

Differentiation and Maturation II

• induction - cell-cell interactions via secretion of chemicals that influence the fate of neighbouring cells

• if immature cells removed from region, they will be replaced with subsequent neurons that will acquire same characteristics

• because of this (pluripotency) they can be used therapeutically to help tackle neurodegenerative conditions

4. Synaptogenesis and Synaptic Pruning

Synaptogenesis:

• growing end of axon known as growth cone - growth cones are attracted to chemicals released from target sites

• once successful contact has been made between neurons, axon and target induce each other to construct machinery to help attach to one another and to form synapse

• once synapse formed, they are sluggish and slow in firing

Synaptogenesis and Synaptic Pruning II

Synaptic Pruning:

• successful synapses are those who are active and maintained and strengthened

• those not successful are eliminated - synaptic pruning

• due to the ability to constantly form new synapses and prune others there is plasticity

Synaptic Pruning - Gogtay et al., 2004

• brain scans of 4-25 year olds every 2 years and found grey matter thickens in childhood but begins to thin out

• synaptic pruning starting from back to front by early adulthood

• increase in white matter (myelination) which peaks in adulthood

• process completed earlier in girls than in boys

5. Cell Death

• first noticed by Viktor Hamburger in chicks but initially dismissed → chick embryos has 20,000 motor neurons shortly after egg laid, but second week of incubation dropped to 12,000

• apoptosis (Kerr et al., 1972) - active process, cells that undergo apoptosis are expressing genes that enable them to die (caspases)

• when axons initially reach targets, they form synapses with several cells = overabundance, many will not form active synapses and will be eliminated - Neural Darwinism

Which neurons will live and which neurons will die?

• proteins secreted by target cells promote the survival and growth of neurons - survival signals

• there are several of these proteins, a family of these factors named neurotrophic factors

• in order to avoid apoptosis a neuron will need:

  → neurotrophins from its target cells

  → active communication with other neurons which strengthens synapses

6. Myelination

• process of glia form fatty sheath that covers axons

• speeds up the transmission of neural impulses

• first occurs in spinal cord and then in hindbrain, midbrain and forebrain (back-front)

• slow process - occurs for decades, depending on region

Does the brain produce new neurons in adulthood?

neurogenic regions in the adult human brain:

• olfactory epithelium contain cells that continuously divide to provide new neurons, and replace damaged ones (Bedard & Parent, 2004)

• cells produced in subventricular zone (SVZ) of the lateral ventricles migrate to replace interneurons in adult olfactory bulb

• long path of migration towards the olfactory bulb is called the Rostral Migratory Stream (RMS) (Altman, 1969)

Rostracl Migratory Stream (RMS)

• newborn cells from subventricular zone migrate to olfactory bulb and become interneurons

• astrocytes wrap around the migrating neurons to create a ‘pipeline’ and keep them on right path

• occurs throughout life

Hippocampus and Cerebral Cortex

Hippocampus:

• the granular layer of the dentate gyrus of the hippocampus, was the first neurogenic area to be discovered (Altman & Das, 1965)

• new neurons are created and added to dentate gyrus throughout life

Cerebral cortex:

• very few adult-born neurons in cortex, which are created in SVZ but still not much is known

• neurogenesis can be induced by injury but depends on extent of injury

Recovering following injury

• better in younger brains and better in periphery than in brain

• mechanisms mainly involve new branching of axons and dendrites → collateral spouting:

• new branches formed by non-damaged axons attach to vacant spots of dendrites and cell bodies

• cells secrete neurotrophins that allow it to occur

Brain adaptations occur throughout life

• blind people since infancy = enhanced tactile (finger sensitivity and auditory ability)

• deaf people have better sense of touch and vision

• brain adapts according to environmental stimuli → neuroplasticity

Blindness (Burton et al., 2002)

• researchers asked sighted and blind people to feel braille letters or other items and say if they were same or different

• blind people performed better

• PET and fMRI scans indicated substantial activity in occipital cortex of blind people

• auditory stimuli produced increased responses in visual areas of cortex

Music Training

• musicians have larger brain areas responsible for hearing and finger control

• MRI scans reveal:

  → temporal cortex of professional musicians in right hemisphere is 30% larger than non-musicians

• thicker grey matter in part of brain responsible for hand control and vision of professional piano platers

More vs Fewer Experiences

• rats raised in enriched environment develop thicker cortex and have increased dendritic branching - Rosenzweig & Bennet, 1980

• much of this enhancement due to physical activity

• increased dendritic branching correlated with improved ability to learn

Critical Periods

• period of time when the brain is most sensitive to specific experience

• absence of visual stimuli can lead to blindness, lack of language exposure can lead to inability to use language