Mar 26

Overview of Synaptic Changes

  • Facilitation and Depression

    • The figure presents three sections demonstrating different calcium conditions affecting excitatory postsynaptic potentials (EPSPs).

    • Sections of the Figure:

    1. Low Calcium Solution (Section A)

      • Initial EPSP is noted.

      • Subsequent EPSPs show greater amplitude.

      • A test pulse is higher than the initial EPSP, indicating facilitation.

    2. High Calcium Solution (Section B)

      • Initial EPSPs have high amplitudes.

      • Subsequent EPSPs demonstrate depression (smaller amplitudes).

      • No test pulse is present because vesicles are depleted.

    3. Normal Physiological Calcium (Section C)

      • Initial EPSP is recorded followed by subsequent EPSPs which also show increased amplitudes, but taper off.

      • Test pulse is lower than the initial EPSP, indicating depression.

  • Key Insights:

    • Facilitation occurs in low calcium conditions, while depression is more pronounced in high calcium conditions. Normal conditions exhibit both effects.

Facilitation

  • Definition:

    • A short-term increase in synaptic strength during repeated stimulation.

  • Mechanism:

    • Residual calcium accumulates in the presynaptic terminal, boosting the release probability of neurotransmitters during subsequent EPSPs as calcium levels rise but fade back to baseline over time.

  • Supporting Evidence:

    • Calcium chelators reduce facilitation.

    • Calcium currents increase during stimulus trains.

Depression

  • Definition:

    • A temporary decrease in synaptic strength that occurs with continued stimulation.

  • Causes:

    • Large initial neurotransmitter release that depletes vesicles in presynaptic cells.

    • Reduced presynaptic calcium current contributing to lower release probability.

  • Recovery Mechanism:

    • Vesicles are replenished alongside calcium returning to baseline levels.

Augmentation

  • Definition:

    • An intermediate increase in synaptic strength over seconds, distinct from facilitation.

  • Mechanism:

    • Result of increased release probability due to additional presynaptic action potentials.

  • Key Difference from Facilitation:

    • Unlike facilitation, there's no change in the total number of available vesicles.

Post-tetanic Potentiation (PTP)

  • Definition:

    • Long-lasting increase in neurotransmitter release after high-frequency tetanic stimulation.

  • Mechanism:

    • Resulting from increased presynaptic calcium levels and enhanced vesicle release probability.

    • Total number of release-ready vesicles increases as well.

  • Magnitude Factors:

    • Relies on stimulation frequency and train duration.

  • Decay Phases:

    • Fast Phase: Release probability returns to baseline quickly, similar to augmentation.

    • Slow Phase: Vesicle pool numbers recover more gradually.

Long-Term Plasticity

  • Definition:

    • Persistent synaptic changes resulting from repeated synaptic activity; affects synaptic strength for hours to days.

  • Importance:

    • Key for memory and learning processes.

Long-Term Potentiation (LTP)

  • Definition:

    • An increase in synaptic strength caused by a large influx of postsynaptic calcium.

  • Consequences:

    • Activation of AMPA receptors at postsynaptic sites increases sensitivity.

Long-Term Depression (LTD)

  • Definition:

    • A decrease in synaptic strength due to smaller postsynaptic calcium signals.

  • Characterization:

    • Involves removal of AMPA receptors from postsynaptic sites.

Temporal Differences in Forms of Plasticity

  • Visualize Plasticity Over Time:

    • Facilitation occurs within milliseconds.

    • Augmentation and depression occur over seconds.

    • PTP persists for minutes.

    • LTP extends for hours to days.

Memory Formation and Synaptic Plasticity

  • Importance of Hippocampus:

    • Essential in memory and learning, linked to findings from Brenda Milner's work on patient H.M.

    • Concept of "cells that fire together wire together" emphasized as significant in memory studies.

Brenda Milner’s Contributions

  • Noteworthy Case Study:

    • Patient H.M. had significant memory loss following a surgical procedure.

    • Memory studies revealed distinctions between short-term and long-term memory.

  • Discoveries:

    • H.M. could retain immediate information through repetition but couldn't create new long-term memories.

    • Distinction between declarative memory (facts and information) and procedural memory (skills) emerged through her studies, showcasing different brain mechanisms involved.

Trisynaptic Loop in Hippocampus

  • Key Components:

    • The pathway involves entorhinal cortex, dentate gyrus, CA3 pyramidal cells, and CA1 pyramidal cells.

    • Importance for memory consolidation emphasized.

Mechanisms of LTP and LTD

  • LTP Mechanisms:

    • Calcium influx activates signaling cascades leading to AMPA receptor insertion.

    • Associative LTP:

    • Coincidence of signals from two inputs necessary for LTP, underpinning associative learning principles.

  • LTD Mechanisms:

    • Various pathways including NMDA dependent, metabotropic glutamate receptor dependent, and endocannabinoid signaling.

Maladaptive Plasticity Examples

  • Addiction:

    • Linked with increased synaptic strength through LTP mechanisms.

  • Phantom Limb Pain:

    • Occurs due to mismatched sensory inputs and neural rewiring following limb loss.

  • Epilepsy:

    • Characterized by hypersensitivity in neuronal circuits, most commonly treated with cortical surgery.

  • Tinnitus:

    • Results from compensatory reorganization in the auditory cortex after hearing loss.

  • Dystonia:

    • Overlapping motor maps leading to motor control issues due to repeated muscle use.

Conclusion

  • Importance of Understanding Maladaptive Plasticity:

    • Recognition of how synaptic changes contribute to various neurological disorders.

  • Engaging in volunteer opportunities and community involvement recommended for student development.

  • Quiz Preparation:

    • Key terms and concepts reviewed, such as activation of signaling pathways and receptor types.

Miscellaneous Notes

  • The visual representations of EPSC (excitatory postsynaptic currents) and their correlations with synaptic changes are used to further emphasize the mechanisms discussed.

  • Additional context provided includes volunteer opportunities emphasizing community engagement and benefits for future academic and career pathways.