2. Academic Validation
  3. Neuronal growth patterns and synapse formation are mediated by distinct activity-dependent mechanisms

Neuronal growth patterns and synapse formation are mediated by distinct activity-dependent mechanisms

  • Sci Rep. 2025 May 19;15(1):17338. doi: 10.1038/s41598-025-00806-9.
Matthew Yacoub # 1 2,  Fahad Iqbal # 1 2,  Zainab Khan 1 2,  Atika Syeda 3,  Thomas Lijnse 4 5,  Naweed I Syed 6 7 8 9
Affiliations

Affiliations

  • 1 Hotchkiss Brain Institute, University of Calgary, Calgary, AB, T2N 4N1, Canada.
  • 2 Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, T2N 4N1, Canada.
  • 3 HHMI Janelia Research Campus, Ashburn, VA, 20147, USA.
  • 4 School of Mechanical and Materials Engineering, University College Dublin, Dublin, D04 V1W8, Ireland.
  • 5 UCD Centre for Biomedical Engineering, University College Dublin, Dublin, D04 V1W8, Ireland.
  • 6 Hotchkiss Brain Institute, University of Calgary, Calgary, AB, T2N 4N1, Canada. nisyed@ucalgary.ca.
  • 7 Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, T2N 4N1, Canada. nisyed@ucalgary.ca.
  • 8 Department of Cell Biology and Anatomy, University of Calgary, Calgary, AB, T2N 4N1, Canada. nisyed@ucalgary.ca.
  • 9 Cumming School of Medicine, University of Calgary, 3330-Hospital Drive, NW, Calgary, AB, T2N 4N1, Canada. nisyed@ucalgary.ca.
  • # Contributed equally.
PMID: 40389417 DOI: 10.1038/s41598-025-00806-9
Abstract

All brain functions in Animals rely upon neuronal connectivity that is established during early development. Although the activity-dependent mechanisms are deemed important for brain development and adult synaptic plasticity, the precise cellular and molecular mechanisms remain however, largely unknown. This lack of fundamental knowledge regarding developmental neuronal assembly owes its existence to the complexity of the mammalian brain as cell-cell interactions between individual neurons cannot be investigated directly. Here, we used individually identified synaptic partners from Lymnaea stagnalis to interrogate the role of neuronal activity patterns over an extended time period during various growth time points and synaptogenesis. Using intracellular recordings, microelectrode arrays, and time-lapse imaging, we identified unique patterns of activity throughout neurite outgrowth and synapse formation. Perturbation of voltage-gated CA2+ channels compromised neuronal growth patterns which also invoked a protein kinase A mediated pathway. Our findings underscore the importance of unique activity patterns in regulating neuronal growth, neurite branching, and synapse formation, and identify the underlying cellular and molecular mechanisms.

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