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Optogenetically Controlled Activity Pattern Determines Survival Rate of Developing Neocortical Neurons.

I Emeline Wong Fong Sang1, Jonas Schroer1, Lisa Halbhuber1

  • 1Institute of Physiology, University Medical Center Mainz, Johannes Gutenberg University, Duesbergweg 6, 55128 Mainz, Germany.

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Summary

The temporal pattern of electrical activity, not just the level, is crucial for neuronal survival during development. Physiological burst firing promotes neuron survival, while non-physiological patterns increase cell death rates.

Keywords:
Baxactivity patternapoptosisburstcortexdevelopmentmouseoptogenetics

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Cell Biology

Background:

  • Programmed cell death (apoptosis) is a significant process during neuronal development.
  • Neuronal activity levels influence apoptosis rates, with higher activity generally promoting survival.

Purpose of the Study:

  • To investigate whether the temporal pattern of neuronal activity, in addition to its level, impacts neuronal survival rates.
  • To differentiate the effects of activity level versus firing patterns on programmed cell death in developing neurons.

Main Methods:

  • Optogenetic control of spontaneous activity in synaptically-isolated primary cortical neurons in developing cultures.
  • Modulation of single-neuron firing patterns, specifically comparing physiological burst firing with non-physiological single-pulse stimulation.
  • Assessment of neuronal survival, intracellular calcium levels, gene expression of activity-dependent targets, Bax/BCL-2 ratio, and caspase 3/7 activity.

Main Results:

  • Action potential firing by primary cortical neurons significantly promotes neuronal survival during development.
  • Physiological burst firing patterns enhanced neuronal survival compared to non-physiological single-pulse patterns, even with stable overall activity levels.
  • Burst firing increased intracellular calcium, upregulated activity-dependent gene expression, decreased the Bax/BCL-2 ratio, and reduced caspase 3/7 activity, indicating reduced apoptosis.

Conclusions:

  • The temporal pattern of action potential firing is a critical determinant of neuronal survival versus cell death during cortical development.
  • Beyond the general pro-survival effect of firing, specific physiological firing patterns are essential for regulating apoptosis.
  • These findings highlight the importance of precise electrical activity timing for healthy neuronal development and survival.