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Redundant Postsynaptic Functions of SynCAMs 1-3 during Synapse Formation
Daniel K Fowler1, James H Peters2, Carly Williams3
1Department of Biology, Institute of Neuroscience, University of OregonEugene, OR, USA; Department of Integrative Physiology and Neuroscience, Washington State UniversityPullman, WA, USA.
Frontiers in Molecular Neuroscience
|February 16, 2017
Summary
Synaptic cell adhesion molecules 1-3 (SynCAM1-3) are collectively essential for synapse formation. Their redundancy masked their postsynaptic role in regulating synapse number and size in hippocampal neurons.
Area of Science:
- Neuroscience
- Molecular Biology
- Synaptic Plasticity
Background:
- Investigating synaptogenic adhesion molecules is challenging due to functional redundancy.
- Synaptic cell adhesion molecules 1-3 (SynCAM1-3) are implicated in synapse formation but their endogenous roles are unclear.
- SynCAM1-3 are expressed pre- and postsynaptically and share homologous domains.
Purpose of the Study:
- To elucidate the endogenous functions of SynCAM1-3 during synapse formation in hippocampal neurons.
- To determine if SynCAM1-3 exhibit functional redundancy in vivo.
- To identify the cellular compartment (pre- or postsynaptic) responsible for SynCAM1-3 function.
Main Methods:
- Utilized triple knockdown (KD) of SynCAM1-3 using chained artificial microRNAs (amiRNAs) in cultured hippocampal neurons.
- Performed electrophysiological recordings to assess quantal release events and synapse size.
- Employed a combinatorial, mosaic lentiviral approach to compare wild-type (WT) and SynCAM1-3 KD neurons within the same culture.
Main Results:
- Triple KD of SynCAM1-3 significantly reduced synapse density and increased synapse area.
- Electrophysiology confirmed an increase in synapse size upon SynCAM1-3 depletion.
- Mosaic analysis revealed that SynCAM1-3 function postsynaptically to regulate synapse number and size.
Conclusions:
- SynCAM1-3 are functionally redundant and collectively necessary for proper synapse formation.
- The functional redundancy of SynCAM1-3 has previously obscured their critical role in synaptogenesis.
- SynCAM1-3 exert their synaptogenic effects through postsynaptic mechanisms, controlling synapse number and size.
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