Lecture 3.1 3.2

Biology of Learning

  • Learning involves physiological changes.

  • Pavlov's classic conditioning: pairing stimuli changes response.

  • Hebb's Rule (1949): "Cells that fire together, wire together."

  • Studies of Aplysia: Simple nervous system ideal for studying learning.

    • Eric Kandel (Nobel Prize 2000): experience-driven synaptic changes.

Studying Aplysia

  • Gill Withdrawal Response: Demonstrates habituation and sensitization.

  • Habituation: Decreased response to repeated stimuli.

  • Sensitization: Increased response after a strong stimulus.

  • Short Term Habituation (STH): Repeated stimulation reduces neurotransmitter release.

    • Fewer vesicles releasing neurotransmitters in response to Ca^{++} influx.

  • Sensitization in Aplysia: Strong stimuli release serotonin. K^+ channels are blocked, prolonging neurotransmitter release.

    • Short-term: longer neurotransmitter release.

    • Long-term: new protein synthesis and gene expression changes.

Long Term Potentiation (LTP)

  • Persistent strengthening of synapses based on recent activity.

  • Mechanism: High-frequency stimulation leads to potentiation via calcium influx through NMDA receptors.

  • Characteristics of LTP:

    • Specificity: Only active synapses are strengthened.

    • Cooperativity: Simultaneous stimulation of multiple axons enhances LTP.

    • Associativity: Pairing weak and strong inputs enhances response to weak inputs.

Biochemistry of LTP

  • Glutamate: Primary excitatory neurotransmitter.

  • AMPA and NMDA receptors mediate synaptic changes.

  • Process:

    • Glutamate binds to AMPA receptors, allowing sodium influx.

    • Depolarization and calcium influx through NMDA receptors.

    • Calcium activates signaling pathways, enhancing synaptic strength and growth.

  • Maintenance of LTP: Maintained by AMPA receptors; NMDA receptors not involved.

  • Cannabis disrupts LTP by inhibiting calcium channels.

Long Term Depression (LTD)

  • Prolonged decrease in synaptic response due to low activity rates.

  • Compensatory mechanism to balance synaptic strengthening.

Neural Development

  • Brain is dynamic, influenced by genetic programming and environmental interactions.

  • Initial development:

    • Cell multiplication.

    • Induction of the neural plate.

  • Development of neurons:

    • Proliferation: Rapid increase in cell numbers.

    • Migration: Movement of neurons to final locations.

    • Aggregation: Alignment of neurons to form structures.

    • Axon growth: Formation of axons and dendrites.

Multiplication

  • Reproduction starts with a single cell.

    • Ovum (egg) + sperm = Zygote (fertilized egg).

  • Growth begins through cell division.

Induction

  • Nervous system development begins around 2-3 weeks of embryonic life.

  • Key early steps:

    • Dorsal surface thickens to form the neural tube.

    • Anterior end differentiates into hindbrain, midbrain, and forebrain.

    • Remaining neural tube develops into the spinal cord.

Development of Neurons

  • Identity: Cells differentiate into specific types.

  • Travel: Cells migrate to appropriate locations.

  • Relations/Connectivity: Establishing functional connections.

  • Proliferation: Production of new cells early in life.

    • Cells along ventricles divide into stem cells and neurons/glial cells.

Migration

  • Neurons and glia migrate to final destinations.

  • Key features:

    • Some cells arrive at their destination in adulthood.

    • Occurs in various directions.

    • Guided by chemical signals (immunoglobulins and chemokines).

Aggregation

  • Neurons align and cluster in the same area.

  • Controlled by Neural Cell Adhesion Molecules (NCAMs).

  • NCAMs help neurons recognize and bind.

Axon Growth

  • After aggregation, neuron differentiates, developing axon and dendrites.

  • Axon grows first, often during migration.

  • Growth cone directs axon growth.

  • Accurate axon targeting is vital.

Myelination

  • Glia cells produce myelin sheath around axons.

  • Increases speed of neural impulses.

  • Occurs in spinal cord, progresses to hindbrain, midbrain, and forebrain.

Synaptogenesis

  • Final stage: Formation of synapses.

  • Axons initially form synapses with multiple cells.

  • Postsynaptic cells strengthen useful connections and eliminate weaker ones.

  • More active in early development.

How Axons Find Targets

  • Chemoaffinity: Target areas release chemical signals.

  • Axons attracted or repelled based on chemical compatibility.

  • Disruptions can lead to developmental problems.

Neuroplasticity

  • Brain reorganizes in response to experiences.

  • Axons and dendrites modify structure and connections.

  • Dendrites grow new spines.

  • Animal evidence: Neuron shape changes over time.

  • Environmental influence: Stimulating environment enhances sprouting.

Limited Plasticity

  • Ocular dominance columns influenced only in early life.

  • Digital stimulation in older primates: Expansion in somatosensory cortex.

Human Neuroplasticity

  • Lifelong, but types dominate at different stages.

    • Developmental plasticity: During normal brain development.

    • Adaptive plasticity: Compensates for injury.

Process Behind Plasticity

  • Synaptic Rearrangement: Focuses neuron output for efficiency.

  • Neural Reorganization:

    • Rapid Change: Strengthens existing connections.

    • Gradual Change: Establishes new connections.