Activity-dependent maturation of climbing fiber to Purkinje cell synapses during postnatal cerebellar development

Area of Science:

• Neuroscience
• Developmental Biology
• Molecular Biology

Background:

• Cerebellar Purkinje cells (PCs) receive input from multiple climbing fibers (CFs) during early development.
• CFs undergo a process of elimination and strengthening, resulting in a single CF innervating each PC.
• P/Q-type voltage-dependent calcium channels (VDCCs) are known to play a role in this process.

Purpose of the Study:

• To investigate the specific role of postsynaptic P/Q-type VDCCs in Purkinje cells (PCs) during CF synapse elimination and rearrangement.
• To determine if calcium influx into PCs is critical for the selective strengthening and translocation of CFs.

Main Methods:

• Generation of Purkinje cell-selective knockout mice lacking the Ca(v)2.1 subunit of P/Q-type VDCCs (PC-Ca(v)2.1 KO).
• Whole-cell recordings from PCs in cerebellar slices to analyze CF-mediated excitatory postsynaptic currents.
• Morphological analysis to examine CF innervation patterns on PCs.

Main Results:

• PC-Ca(v)2.1 KO mice exhibited significant defects in the selective strengthening of single CFs during the first postnatal week.
• CF synapse elimination, particularly the early phase (P7-P12), was severely impaired in PC-Ca(v)2.1 KO mice.
• Abnormal translocation of multiple CFs to PC dendrites was observed in PC-Ca(v)2.1 KO mice.

Conclusions:

• Calcium influx through P/Q-type VDCCs into Purkinje cells is indispensable for the selective strengthening of single climbing fibers.
• This calcium influx is crucial for the early phase of CF synapse elimination.
• Postsynaptic P/Q-type VDCCs regulate the selective translocation of strengthened CFs to PC dendrites.