Chapter 23 Outline

Neurodevelopment

• Adult Brain: has precise interconnections among 85 billion neurons

• Brain Development: ectoderm → tube → CNS

  • Neurogenesis, synaptogenesis, pathway formation: connections formed and modified

• Wiring: establishing correct pathways and targets

  • Fine-tuning: based on experience

The Genesis of Neurons

• Steps Pre-Birth: Neurogenesis, Neuronal selection, ventricular migration, differentiation and myelinization, & synaptogenesis

• Steps Post-Birth: Neurogenesis and synaptogenesis (decreased) & apoptosis/pruning

First Stage of Development: Cell Proliferation

• Steps:

  • A progenitor cell in the ventricular zone extends a process that reaches upward toward the pia

    • Multipotent Radial Glia Cells: progenitor cells that can become other cell types when divided

  • The nucleus of the progenitor cell migrates upward from the ventricular zone towards the marginal zone

  • DNA is copied in the marginal zone

  • The nucleus returns to the ventricular zone with (2x DNA)

  • The cell retracts its process from the pial surface

  • The cell divides

    • Symmetrical: becomes another radial glia

    • Asymmetrical: becomes another cell type

Second Stage of Development: Cell Migration

• Cell Migration

  • 2/3: Neural precursors follow radial glia

    • Cell Types: Pyramidal cells & astrocytes

  • 1/3: Neural precursors migrate laterally

    • Cell Types: Inhibitory interneurons & oligodendroglia

• Layers of Cortex

  • Cortical Plate: neural precursor cells destined to become the adult cortex cross the subplate and form this

  • Inside Out Layering: Younger cells fill the inner layers, while older cells fill the out layers

• Differentiation of Cortical Areas

  • Cortical Quilt: subplate layer of earliest born neurons contain the instructions for the assembly

  • Radial Unit Hypothesis: radial glial guides replicate a cortical protomap in the ventricular zone

• Importance of Transcription Factors in Neuronal Differentiation

  • Experiment:

    • EMX2 & PAX6: complimentary gradients of transcription factors that help in cell differentiation from a limited number of genes

    • Removal of EMX2: increased motor and somatosensory cell densities, decreased visual cell density

    • Removal of PAX6: increased visual density, decreased motor and somatosensory cell densities

  • Lateral Migration: transcription factors are important for neurons that migrate laterally to find their place

• Importance of Input from the Thalamus in Differentiation

  • Differentiation of Monkey Striate Cortex: requires LGN input during fetal development

  • Thalamic Input: helps neural organization

Adult Neurogenesis

• Atomic Bomb: granular cells of the dentate gyrus containing C-14 suggests continual neurogenesis post adolescence

Third Stage of Development: Cellular Differentiation

• Cell Differentiation: cell takes on the appearance and characteristics of a neuron

• Spatiotemporal Gene Expression: determines specific cell pattern

• Semaphorin 3A: concentrations cause attraction (high) or repulsion (low) of the growing neurites so they grow in the correct directions

Fourth Stage of Development: Maturation

• Maturation: Intermediate stage where dendrites form & axons begin to elongate

• Growth Cone: the growing tip of a neurite

  • Function: Identifies an appropriate path for neurite elongation

• Lamellipodia: flat membrane w/ filopodia

  • Filopodia: sense and grip the ECM

    • Lamin: uses integrins (gripping proteins)

• Pioneer Axons: axons that stretch as the nervous system expands and guides their later developing neighbor axons

  • Fasciculation: causes axons growing together to stick together

    • CAMs: Cell Adhesion Molecules bind the axons

• Pathway Formation

  • Axon Elongation: maturation of axons

  • Pathway Selection: which direction to go

  • Target Selection: where to go

  • Address Selection: which specific area to go (connections)

• Axon Guidance

  • Pioneer Axons & Development: come early in development; stretch as nervous system expands

  • Guidance Cues

    • Chemoattractants: molecules that make certain growth cones turn towards them

      • Ex: Netrin

    • Chemorepellents: molecules that make certain growth cones go away from them

      • Ex: Slit

Fifth Stage of Development: Synaptogenesis

• Synapse Formation: when the growth cone comes in contact with its target, a synapse is formed

• Steps:

  • Dendritic filopodium contacts axon

  • Synaptic vesicles and active zone proteins recruited to presynaptic membrane

  • Receptors accumulate on postsynaptic membrane

Sixth Stage of Development: Synaptic Pruning

• Programmed Cell Death: entire populations of neurons are eliminated during pathway formation if they are deemed unimportant

  • Apoptosis: systematic disassembly of the neuron

  • Necrosis: cell death due to damage

  • Trophic Factors: substances that sustain neurons by being taken up retrogradely

    • Ex: NGF, BDNF, NT3, NT4

    • Signal: through Trk receptors

• Synaptic Pruning: synaptic capacity is greatly decreased as nervous system matures

  • Muscle Fibers: initial polyneuronal innervation is replaced by synaptic input from a single alpha motor neuron

• Hubel and Wiesel

  • Ocular Dominance Columns: stripes of neurons in V1 that receive input from either the left or right eye

  • Ocular Deprivation Studies: monkeys, who had one eye covered during the critical period, had little to no ocular dominance column for that eye

  • Synaptic Competition: a change from one pattern of synapses to another

    • Ex: 3-3 → 5-1

  • Critical Period: specific times when developmental fate is influenced by the environment

Hebb’s Law

• Hebb’s Law: Cells that “fire” together, “wire” together

  • Weak Synapse: cells that are out of sync, delink

Long-Term Synaptic Potentiation

• Long-Term Potentiation (LTP): strengthening of synaptic transmission from strong NMDA receptor activation, results in an influx of Ca²⁺

  • AMPA: new AMPA receptors inserted into the synaptic membrane

• Long-Term Depression (LTD): weakening of synaptic transmission from low NMDA receptor activation, results in less influx of Ca²⁺

  • AMPA: loss of AMPA receptors from the synapse and synapse elimination over time