Presynaptic development is controlled by the core active zone proteins CAST/ELKS

Area of Science:

• Neuroscience
• Molecular Biology
• Developmental Biology

Background:

• Presynaptic active zone (AZ) proteins, like CAST/ELKS, have complex roles in neuronal development.
• Understanding CAST/ELKS function in vivo during early circuit maturation is crucial.

Purpose of the Study:

• To investigate the roles of CAST/ELKS in glutamatergic synapse development and presynaptic function.
• To analyze the impact of CAST/ELKS loss on the calyx of Held terminal during early circuit maturation.

Main Methods:

• Utilized CAST knockout (KO) and ELKS conditional KO (CKO) mice.
• Performed morphological analysis using confocal microscopy.
• Assessed AZ ultrastructure and synaptic function via patch-clamp recordings.

Main Results:

• CAST/ELKS deletion reduced calyx surface area and volume but increased AZ size.
• Loss of CAST/ELKS decreased all presynaptic Ca_V 2 channel subtypes and their currents.
• Synaptic transmission and plasticity remained unaffected despite these molecular changes.

Conclusions:

• CAST/ELKS positively regulate presynaptic growth and suppress AZ expansion and Ca_V 2 channel levels during development.
• CAST/ELKS are involved in regulating presynaptic morphology and Ca_V 2 channel subtypes.
• Developmental compensation mechanisms preserve synaptic transmission in the absence of CAST/ELKS.