SynDIG4/Prrt1 Is Required for Excitatory Synapse Development and Plasticity Underlying Cognitive Function

Area of Science:

• Neuroscience
• Molecular Biology
• Synaptic Plasticity

Background:

• Synaptic plasticity, particularly involving AMPA receptors (AMPARs), is vital for learning and memory.
• Synapse differentiation-induced gene 1 (SynDIG1) regulates excitatory synapse strength and number.
• The role of the related protein SynDIG4 (Prrt1) in synaptic function remains less understood.

Purpose of the Study:

• To investigate the function of SynDIG4 in regulating AMPAR properties and synaptic plasticity.
• To determine the impact of SynDIG4 deficiency on synaptic strength, long-term potentiation (LTP), and cognitive behavior.

Main Methods:

• Utilized SynDIG4 knockout (KO) mouse models.
• Employed immunocytochemistry and electrophysiology to assess synaptic properties.
• Conducted cognitive assays to evaluate learning and memory deficits.

Main Results:

• SynDIG4 KO mice exhibited weaker excitatory synapses and reduced mEPSC amplitude.
• Adult SynDIG4 KO mice showed a complete loss of LTP and impaired cognitive function.
• SynDIG4 was found to colocalize with the GluA1 AMPAR subunit at extrasynaptic sites.

Conclusions:

• SynDIG4 modulates AMPAR gating in a subunit-dependent manner.
• SynDIG4 is essential for maintaining extrasynaptic AMPAR pools critical for synapse development and function.
• SynDIG4 plays a significant role in higher-order cognitive plasticity.