The TrkC-PTPσ complex governs synapse maturation and anxiogenic avoidance via synaptic protein phosphorylation

Area of Science:

• Neuroscience
• Molecular Biology
• Synaptic Plasticity

Background:

• Precise organization of synaptic terminals is essential for brain function.
• Postsynaptic TrkC, a receptor tyrosine kinase, organizes excitatory synapses via interaction with presynaptic PTPσ.
• TrkC's canonical role involves neurotrophin-3 signaling.

Purpose of the Study:

• To investigate the synaptic organizer function of TrkC independently of its neurotrophin-3 receptor role.
• To elucidate the specific contribution of the TrkC-PTPσ interaction to synapse organization and function.

Main Methods:

• Generation of mice with TrkC point mutations that abolish PTPσ binding.
• Analysis of excitatory synapse structure, function, and protein phosphorylation in mutant mice.
• Behavioral testing of mutant mice to assess social responses and avoidance.

Main Results:

• Mutant mice exhibited abnormal synaptic vesicle clustering and postsynaptic density elongation.
• Synapses showed increased silent synapses, reduced active synapses, enhanced basal transmission, and impaired release probability.
• Aberrant synaptic protein phosphorylation was observed, without affecting neurotrophin signaling.

Conclusions:

• The TrkC-PTPσ complex is crucial for the maturation, but not the initial formation, of excitatory synapses.
• Dysregulation of this complex impacts synaptic protein phosphorylation, leading to behavioral abnormalities relevant to neuropsychiatric disorders.