Mar 13

Final Unit on Synaptic Plasticity

Introduction to Synaptic Plasticity

  • Definition: Synaptic plasticity refers to the ability of synapses to strengthen or weaken over time, which is critical for learning and memory.

Overview of Long-Term Depression (LTD)

  • Concept of LTD: A phenomenon characterized by a long-lasting decrease in synaptic strength.

  • Duration: Can last for days, hours, weeks, or even years.

  • Information Retention: LTD is essential for the brain to prioritize informative signals in terms of synaptic connections.

Importance of Informative Signals

  • Communication Analogy:

    • When communication is not informative, it resembles excess noise; thus, the brain adjusts responses.

    • Example: The speaker likens it to how his grandfather selectively listened to the grandchildren over the grandmother.

Forms of Long-Term Depression

  • Types Discussed: Two specific forms of LTD will be detailed in the lecture.

Spike Timing Dependent Plasticity (STDP)

  • Description: A significant concept in both learning and development related to the timing of spikes in neurons.

  • Mechanism: Explains how the order of activity between pre- and postsynaptic neurons affects synaptic strength.

  • Experiments & Shows Importance: Pre- and postsynaptic activity order influences synaptic response.

  • Example Situations:

    • If postsynaptic activity occurs before presynaptic activity, LTD occurs.

    • In contrast, when presynaptic activity comes first, Long-Term Potentiation (LTP) may result.

Experimental Evidence Using Hippocampal Slices

  • Inducing LTD Studies:

    • Strong depolarization of postsynaptic cells along with weak presynaptic stimulation can induce LTD affecting the excitatory postsynaptic potential (EPSP).

  • Properties of LTD: These adaptations can be explained by three key properties: associativity, specificity, and coincidence detection.

Comparison Between LTP and LTD

  • Method of Induction:

    • LTP requires tetanic stimulation (e.g., 100 Hz for 1 second).

    • LTD can be induced through low-frequency stimulation over an extended period (5 Hz for 15 seconds).

  • Outcome after Stimulation:

    • Following prolonged low-frequency stimulation, there can be up to a 50% reduction in the magnitude of postsynaptic responses.

Mechanisms for LTP and LTD

  • LTP Mechanism Overview:

    • Involves NMDA receptor activation and calcium influx that leads to signaling cascades enhancing synaptic transmission by inserting AMPA receptors in the postsynaptic membrane.

  • LTD Mechanism Overview:

    • Involves activation of protein phosphatases leading to the removal of AMPA receptors from the postsynaptic membrane.

    • Calcium acts but leads to different outcomes due to lower levels and duration compared to LTP.

Molecular Pathways in LTD and LTP

  • Calcium's Role:

    • Calcium acts as a second messenger in both LTP and LTD but its concentration and duration determine the outcome.

    • In LTP, considerable calcium influx induces addition of AMPA receptors. In LTD, calcium entry leads to receptor removal.

  • Phosphatases in LTD:

    • Phosphatases like PP1 and PP2B are activated to facilitate receptor internalization.

  • Endocytosis and Vesicle Dynamics:

    • Claffing and other proteins also involved in receptor dynamics during internalization.

Differences Between Brain Regions: Hippocampus vs. Cerebellum

  • Cerebellum's Functionality: Initially known for motor functions, further studies show cognitive roles.

  • LTD in Cerebellum: Requires simultaneous stimulation from both parallel fibers and climbing fibers to induce LTD.

    • The interaction determines synaptic connections strength following stimulation protocols.

Summary of the Cellular Mechanisms

  • LTD Cascade:

    • Involves both AMPA receptors binding glutamate and activating metabotropic glutamate receptors (mGluRs) leading to calcium release from intracellular stores.

    • Requires precise timing for effective synaptic changes based on the overlap of stimulus.

Spike Timing and Neuronal Activity

  • Importance of Timing:

    • Short intervals between pre and postsynaptic activity determine the outcome (LTP or LTD).

  • Behavioral Analysis:

    • Precedence in activation influences whether synaptic strengthening or weakening occurs.

  • Thresholds: If the timing exceeds a given threshold, no significant changes will manifest in synaptic response.

Conclusion

  • Review and Assessment: Quiz scheduled for review of material discussed, stressing understanding of LTD and LTP as well as their roles in behavioral and cognitive functions.