11/8- TD4.2 Interactions Neurons + Oligos (MR)

Neuronal Population Dynamics

• Comparison of Neuronal Populations

  • No significant difference in elongation and contraction dynamics between two neuronal populations.

  • Measurement of segment lengths to assess contraction/elongation.

• Measurement Parameters

  • Change in length measured in micrometers (µm): segments can contract or elongate (5, 10, or 15 micrometers).

  • Elongation observed around 5 µm, while contraction is approximately 2-3 µm.

Statistical Analysis of Dynamics

• Dynamics of Elongation and Contraction

  • Both populations exhibit similar elongation and contraction dynamics.

  • Length of myelin affected equally by both types of events in each population.

• Last Graph Analysis

  • Percentage change calculated from segment lengths:

    • Change: length at p9 - length at p6.

    • Ratio: change divided by initial length at p6 (expressed as a percentage).

  • Importance: Types of dynamics differ based on initial segment lengths and populations.

Oligodendrocyte Ablation Study

• Experimental Setup in Zebrafish

  • Use of photosensitive protein "killer red" for targeted cell ablation via light exposure.

  • Consequence of ablation analyzed in lipid oligodendrocytes.

Observations Post-Ablation

• Axonal Integrity

  • Examination of axons post-ablation: counted axon number pre and post ablation shows no loss in axonal numbers.

  • Morphologically, axons appear normal despite the absence of their myelin sheath post-ablation.

• Neuronal Functionality

  • Although no morphological changes observed, potential functional differences exist due to lack of myelin affecting action potential propagation.

Myelin Reformation Dynamics

• Regeneration After Cell Death

  • After oligodendrocyte death, neighboring oligodendrocytes may extend to fill gaps left by ablated cells.

  • New myelin segments form rapidly after injury within days, indicating effective cellular communication and regeneration processes.

Variation in Myelin Segments

• New myelin segments defined post-ablation:

  • Average lengths of new versus pre-ablation segments appear statistically equivalent, but individual variability exists.

  • Regenerated segments may vary from original lengths (some longer, some shorter).

  • Mechanisms for gap filling by neighboring oligodendrocytes observed, with segments also adjusting positions to maintain node integrity.

Linking Plasticity to Learning

• Investigation on Learning Mechanisms

  • Role of oligodendrocyte plasticity explored in association with motor skill learning and memory.

• Experimental Mouse Model

  • Heterozygous control and knockout mice used to evaluate effects of new oligodendrocyte generation.

  • Conditional knockout prevents formation of new oligodendrocytes but does not affect those already present prior to experimental tamoxifen injection.

• Behavioral Assessments

  • Motor skill learning observed by task completion speed in complex and regular wheel setups.

  • Control mice exhibited more efficient learning behaviors compared to knockout mice, implicating newly formed oligodendrocytes in adaptive learning processes.

Implications for Myelination and Learning

• The study demonstrates that adaptive myelination, correlated with learning capabilities, emphasizes the significance of oligodendrocyte dynamics in functional neuronal plasticity.

Neuronal Population Dynamics

Comparison of Neuronal Populations

• Dynamics Overview: No significant difference was observed in elongation and contraction dynamics across two distinct neuronal populations, suggesting a uniformity in their response mechanisms.

• Measurement Methodology: Segment lengths were meticulously measured to assess contraction and elongation, providing a robust framework for comparative analysis.

Measurement Parameters

• Length Change: The change in length was precisely quantified in micrometers (µm), allowing for detailed tracking of neuronal behavior. Segments observed could contract or elongate by specified amounts: 5, 10, or 15 µm.

• Elongation and Contraction: Elongation was predominantly observed around 5 µm, indicating significant growth potential, while contraction averaged approximately 2-3 µm, demonstrating the dynamic capabilities of the neuronal segments.

Statistical Analysis of Dynamics

• Detailed Dynamics Assessment: Both neuronal populations exhibited statistically similar elongation and contraction dynamics, implying that inherent structural and functional properties may not be significantly influenced by population type.

• Myelin Length Impact: The length of the myelin sheath was affected similarly by elongation and contraction events across both populations, indicating the critical role of myelination in neuronal activity.

Last Graph Analysis

• Change Calculation: Percentage change was meticulously calculated from segment lengths using the formula: Change = length at p9 - length at p6. This analysis reflects the adaptive responses of neuronal segments over the examined period.

• Ratio Calculation: The change was then divided by the initial length at p6 and expressed as a percentage, underscoring the proportionate changes observed in neuronal dynamics.

• Importance of Initial Conditions: The nature of dynamic elongation and contraction appears to vary significantly based on the initial segment lengths and specific neuronal populations involved.

Oligodendrocyte Ablation Study

• Experimental Setup in Zebrafish: Utilized a pioneering approach employing the photosensitive protein "killer red" for targeted ablation of oligodendrocytes through precise light exposure, allowing for controlled experimentation on cellular viability and dynamics.

• Consequences of Ablation: The subsequent analysis focused on lipid oligodendrocytes, providing insights into cellular integrity and plasticity.

Observations Post-Ablation

• Axonal Integrity Assessment: Post-ablation examinations revealed that, despite counting pre and post-ablation axon numbers showing no loss, the morphological analysis indicated normal appearance of axons. This suggests resilience in axonal structures in response to oligodendrocyte loss.

• Neuronal Functionality Consideration: Although morphological integrity was largely maintained, there may exist latent functional discrepancies arising from the absence of myelin, potentially impacting action potential propagation and overall neuronal performance.

Myelin Reformation Dynamics

• Regeneration Processes: Post-oligodendrocyte death, neighboring oligodendrocytes exhibit remarkable plasticity, extending their processes to fill gaps and initiate regeneration of new myelin segments shortly after injury, typically evident within days, which highlights the dynamic communication within glial cells.

• Myelin Segment Characteristics: New myelin segments generated post-ablation were analyzed for structural integrity; the average lengths of regenerated segments were statistically equivalent to those prior to ablation, although marked individual variability was noted. This variability suggests a complex mechanism behind myelin regeneration that adapits to surrounding conditions.

• Gap Filling Mechanisms: Observations indicated that neighboring oligodendrocytes engage in mechanisms allowing for gap filling, including the adjustment of segment positions to preserve the integrity of nodes of Ranvier, essential for efficient neuronal signaling.

Linking Plasticity to Learning

• Investigation into Learning Mechanisms: The role of oligodendrocyte plasticity was thoroughly explored, revealing significant correlations between oligodendrocyte dynamics and motor skill learning and memory consolidation.

• Experimental Mouse Model Utilization: A comprehensive model involving both heterozygous control and conditional knockout mice was employed. The conditional knockout selectively prevents the formation of new oligodendrocytes without affecting pre-existing ones, establishing a framework for evaluating effects on learning and behavior.

• Behavioral Assessments: Extensive behavioral assessments were performed, focusing on motor skill learning metrics, particularly task completion speed in complex versus regular wheel setups. Results indicated that control mice, which benefitted from new oligodendrocyte generation, exhibited more efficient and adaptive learning behaviors in contrast to knockout mice, underscoring the functional significance of newly formed oligodendrocytes in cognitive processes.

• Implications for Myelination and Learning: The findings collectively illustrate that adaptive myelination, intimately correlated with enhanced learning capabilities, emphasizes the critical role of oligodendrocyte dynamics in facilitating functional neuronal plasticity and overall cognitive flexibility.