Development of the Central Nervous System Study Notes

Human Brain Statistics: Weighs approximately $1.5\,kg$ (2% of body weight), contains $86 \times 10^9$ neurons, and trillions of connections.
Influencing Factors: Genetic (chromosomal), environmental (sensory input), biochemical (nutrients), and physical (injury/stroke).
The First 1000 Days: The period from conception to ~2.5 years is the most crucial foundation for brain maturation.
Stem Cells: Categorized as Totipotent, Pluripotent, and Multipotent. They must differentiate, travel to the correct location, and form functional connections.

Induction of the Neural Plate (3 weeks – 3 months): Development of the neural groove, neural crest, and neural tube.
Neural Proliferation (Neurogenesis): Rapid cell division (up to 4 million cells/hour) peaking at 3–4 months. Occurs predominantly around the ventricle.
Migration & Aggregation (3–5 months): Immature cells travel to target locations via radial or tangential migration.
Axon Growth & Synapse Formation (Synaptogenesis): Axons utilize growth cones (filopodia) and guidance molecules to reach targets and establish connections.
Neuron Death (Apoptosis) & Synapse Rearrangement: Programmed cell suicide removes ~50% of excess neurons; microglia clear waste to prevent inflammation.

Migration Types:
- Radial: Movement from the ventricular zone outward.
- Tangential: Movement parallel to the outer wall.
- Somal Translocation: An extension explores cues; the cell body moves along it.
- Radial-glia Mediated: Neurons travel along a matrix formed by radial glial cells.
Aggregation Mechanisms: Facilitated by cell-adhesion molecules and gap junctions.
Chemoaffinity Hypothesis: Postsynaptic surfaces release chemical labels that attract specific growing axons; growth cones are also influenced by signals along the route.
Fasciculation: The tendency of developing axons to follow the paths established by pioneer growth cones.

Induction Defects: Encephalocele (errors ~day 24) and Myelomeningocele/Spina bifida (errors before day 26; linked to folate deficiency).
Proliferation Defects: Microcephaly (too few neurons) and Macrocephaly (excess neurons/fluid).
Migration Defects: Lissencephaly (smooth brain/lack of gyri), Polymicrogyria (too many small gyri), and Neuronal heterotopia (clumps of neurons in the wrong position).
Dendritic/Axonal Defects: Agenesis of Corpus Callosum and various disorders of dendritic branching (e.g., ASD, Fragile X, Rett syndrome).
Death/Refinement Defects: Focal Cortical Dysplasia (excess neurons due to failed apoptosis).
Genie Case Study: Demonstrates that extreme environmental deprivation (isolation, harness restraint) hinders growth, speech, and motor control.

Brain Growth: Volume increases 4x from birth to adulthood, driven by synaptogenesis, myelination, and dendritic branching rather than new neurons.
Myelination: Performed by oligodendrocytes; sensory/motor regions myelinate first, while higher-order association regions continue into the 3rd decade.
Prefrontal Cortex: Shows the most prolonged development; controls planning, inhibition, and working memory.
Perseveration: Demonstrated by the A-not-B task; infants fail to inhibit learned behaviors due to immature prefrontal development.
Critical vs. Sensitive Periods:
- Critical Period: Specific windows where environment exposure is mandatory (e.g., binocular vision 3–8 months).
- Sensitive Period: Times of maximum influence (e.g., language before 7 years).

Adult Neurogenesis: Occurs in the hippocampus (~700 per day) and the striatum; increased by exercise and enrichment.
Neuroplasticity: Cortical reorganization occurs with extensive exposure (e.g., enlargement of finger-hand areas in stringed musicians).
Preterm Birth: Risk of white matter loss and delayed myelination due to reduction in pre-oligodendrocytes (pre-OLs).
Neurodivergence (ADHD/Autism): Viewed as non-pathological variations resulting from altered neurogenesis or migration, often dependent on "environmental fit."
Acquired Brain Injury (ABI): Paediatric injury involves a balance between vulnerable foundations and high potential for neuroplastic compensation.