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Synaptic Plasticity Notes

Introduction

  • Course: NS&B 360 – 01 Neuroplasticity and Neurogenesis in Health and Disease

  • Instructor: Prof. Dr. Clarissa Cavarsan

  • Program: Neuroscience and Behavior

How Environment Shapes the Brain

  • Engages with the concept of neuroplasticity, indicating that brain structure and function are influenced by environmental interactions.

Neurotrophins and Synaptic Plasticity

  • Definition: Neurotrophins are a group of proteins that serve as molecular mediators of behavioral modifications pertaining to environmental interactions.

  • Notable neurotrophins:

    • Nerve Growth Factor (NGF)

    • Brain-Derived Neurotrophic Factor (BDNF)

    • Neurotrophin-3 (NT-3)

    • Neurotrophin-4/5 (NT-4/5)

    • Neurotrophin-6 (NT-6)

    • Neurotrophin-7 (NT-7)

  • Neurotrophins are crucial not only for early nervous system development but also for long-term synaptic plasticity in adults.

Trk Receptors

  • Description: Trk receptors are activated by various neurotrophins and play a significant role in neuroplasticity.

  • Notable Trk receptors include:

    • TrkA (activated by NGF)

    • TrkB (activated by BDNF and NT-4/5)

    • TrkC (activated by NT-3)

Mechanisms of Action of Neurotrophins

  • Activation of Tyrosine Kinase Receptors:

    • Binding of a neurotrophin (ligand) leads to the activation of receptor monomers, promoting dimerization (formation of a pair of receptor molecules) whereby protein kinase domains undergo cross-phosphorylation.

    • This process induces changes in quaternary structure and activates downstream signaling pathways.

  • Primary Effects:

    • Facilitation of neurotransmitter release from the presynaptic terminal.

    • Phosphorylation of NMDA and AMPA receptors in the postsynaptic terminal, enhancing synaptic efficacy.

Role of BDNF in Synaptic Efficacy

  • Long-term Potentiation (LTP): LTP processes lead to increased levels of BDNF and TrkB receptor mRNA, pivotal for maintaining synaptic strength.

  • Experimental evidence shows that tetanic stimulation increases the excitatory postsynaptic potential (EPSP) slope, indicating enhanced synaptic transmission associated with increased BDNF levels.

  • Quantitative Findings:

    • BDNF levels were measured from homogenates of dentate gyrus tissues under both tetanized and untetanized conditions.

Role of NT-3 in Synaptic Efficacy

  • Significance: Recent research highlights NT-3’s involvement in synaptic strengthening, especially its relationship with TrkC receptors.

  • Effects of NT-3:

    • Infusion of NT-3 has shown substantial and lasting enhancements in synaptic transmission, particularly in the Schaffer collateral pathway (vital for memory processes).

Brain Architecture Modifications

  • Yo proposed by Santiago Ramon y Cajal:

    • Information storage in the brain is managed through synaptic transmission strength changes, which can lead to structural alterations.

BDNF and Neurogenesis

  • BDNF plays a crucial role in adult hippocampal neurogenesis within regions like the subventricular zone (SVZ) and subgranular zone (SGZ).

  • Functions of BDNF:

    • Influences both the proliferation of new neurons and their survival/differentiation.

NT-3 and Neurogenesis

  • NT-3 has been associated with neuronal proliferation in the hippocampus and differentiation of neural precursors in the spinal cord.

Neurotrophins in Behavior

  • Neurotrophins (especially BDNF and NT-3) increase during exercise, enhancing synaptic and neuronal plasticity which contributes to learning and memory.

Dual-Receptor System

  • The balance between TrkA, TrkB, and other receptors determines neuronal survival or death, crucial for maintaining plasticity in the nervous system.

    • Pro-neurotrophins: Pro-NGF and pro-BDNF are soluble precursors that also interact with neurotrophin receptors, influencing cell survival and differentiation.

Metaplasticity

  • Definition: Metaplasticity refers to changes in the ability of synapses to undergo plasticity after prior activity (e.g., LTP or long-term depression - LTD).

    • Significantly shapes future synaptic responsiveness and directionality of plasticity.

Practical Implications and Applications

  • Hebbian Principles: "Neurons that fire together wire together" - reflecting the mechanisms of synaptic strengthening through coincident activity.

  • Exercise and Neuroplasticity: Physical activity increases neurotrophin levels, resulting in enhanced cognitive functions, synaptic growth, and neurogenesis in the hippocampus.

  • Neuroplasticity in Learning: Contextual examples include a pianist practicing music, which requires neuroplastic adaptations in terms of memory and motor function within the brain's neural circuits.