Early Neurodevelopment and Stem Cells

Early Neurodevelopment

• Cells must differentiate into specialized types (muscle, liver, neurons, glia), migrate to correct locations, and establish connections with other cells.
• The case of Genie highlights the crucial role of experience in neurodevelopment.
• A zygote (fertilized egg) undergoes rapid division, forming an embryo.

Five Phases of Early Neurodevelopment

• Neural plate formation
• Neural proliferation (rapid neuron increase)
• Migration and aggregation (neurons move to correct positions and connect)
• Axon growth and synapse formation (branching and connection formation)
• Neuron death and synapse rearrangement (pruning of connections for efficiency)

Stem Cells

• Stem cells are undifferentiated cells with the potential to become many different cell types.
• Totipotent stem cells (early embryonic) can develop into any cell type.
• Pluripotent stem cells can develop into most cell types.
• Multipotent stem cells can develop into specific cell types within a class.
• Unipotent stem cells differentiate into only one specific cell type.

Cell Layers and Neural Structures

• Embryonic development involves three germ cell layers: endoderm (gut lining), mesoderm (muscles, connective tissue), and ectoderm (skin, nervous system).
• The neural plate arises from the ectoderm, forming the neural tube (brain and spinal cord).
• The neural crest gives rise to neurons and glia of the peripheral nervous system.

Neural Proliferation, Migration, and Aggregation

• Neural proliferation is the rapid increase in neurons, peaking after the neural tube closes.
• Radial glial cells guide neuron migration from the ventricular zone to their final location.
• Radial migration occurs in a straight line, while tangential migration is perpendicular.
• Somal translocation and glial-mediated migration are mechanisms of neuron movement.
• Aggregation involves the alignment of neurons, facilitated by CAMs, gap junctions, and glial-neuron interactions.

Axon Growth and Synaptogenesis

• Axon growth begins with growth cones, guided by chemoaffinity and topographic gradients.
• Sperry's study on eye rotation showed the importance of chemoaffinity for specific neuron connections.
• Synaptogenesis (synapse formation) is dependent on neuron-neuron and glial cell interaction.

Neuron Death and Neurotrophins

• Neuronal cell death is a crucial part of development, removing incorrect connections. Apoptosis is active and "clean" cell death—necrosis is passive and "dirty".
• Neurotrophins (e.g., NGF, BDNF, GDNF) are vital for neuron growth, survival, and synaptogenesis. Their absence triggers apoptosis.

Postnatal Brain Development

• Postnatal brain development involves continued synaptogenesis, myelination, dendritic branching and regressive changes (synaptic pruning).
• The prefrontal cortex (PFC) develops slowly, contributing to the slow maturation of executive functions.

Experience and Neurogenesis

• Experience significantly influences neurodevelopment (use-it-or-lose-it).
• Critical and sensitive periods during development show experience-dependent neuroplasticity.
• Animal studies demonstrate experience-dependent changes in brain structure and function (ferrets, barn owls, mice). Human studies show enrichment effects on brain areas related to activity (auditory cortex, hippocampus).

Adolescent Brain Development

• Adolescence is a period of significant brain reorganization, involving axonal and dendritic pruning and myelination.
• Functional development in the prefrontal cortex continues into adolescence. Correlates in behavior include enhanced sensitivity to dopamine/oxytocin, novelty seeking, risk-taking.

Adult Neurogenesis

• Adult neurogenesis occurs in distinct brain regions (olfactory bulb and dentate gyrus).
• The olfactory bulb maintains old and introduces new interneurons/neurons.
• The dentate gyrus produces new granule cells for learning and memory.
• Intrinsic (hormones, injury) and extrinsic (enriched environment, exercise) factors contribute to adult neurogenesis.

Atypical Neurodevelopment: ASD

• Autism Spectrum Disorder (ASD) involves difficulties with social interaction and restricted behaviors, often with increased risk of intellectual/learning disability and epilepsy.
• ASD is now diagnosed in more individuals due to changed diagnostic criteria and improved awareness and diagnosis.
• Genetic factors are key to ASD, influencing early or mid-development. Environmental factors also play a role.
• Many genes are impacted in the brains of ASD patients and there are patterns of hyper-connectivity (increased neural fluctuations) and underconnectivity (reduced neural density in the frontal lobe). Oxytocin may be a useful intervention in certain instances and further study is needed.

Atypical Neurodevelopment: Williams Syndrome

• Williams syndrome involves distinct characteristics, notably social behaviour (sociable, empathetic), language ability, musical talent, and an impairment in spatial cognition.
• Chromosomal deletion, specifically on chromosome 7, is associated with the disorder.
• There are anatomical anomalies that may affect specific skill domains.