Enhanced synaptic connectivity and epilepsy in C1q knockout mice.

Area of Science:

• Neuroscience
• Developmental Biology
• Immunology

Background:

• Synapse elimination is critical for mature neural circuit formation during development.
• The complement cascade protein C1q plays a role in synaptic pruning.
• Deficiency in C1q leads to improper refinement of retinogeniculate connections.

Purpose of the Study:

• To investigate the role of C1q in neocortical synapse elimination.
• To determine if C1q deficiency results in enhanced excitatory synaptic connectivity and epileptiform activity.
• To explore the link between C1q, synaptic pruning, and epilepsy.

Main Methods:

• In vivo and in vitro electrophysiological recordings (field potentials, video-EEG).
• Laser scanning photostimulation of caged glutamate and whole-cell recordings to map synaptic connectivity.
• Analysis of axonal bouton density in neocortical neurons.

Main Results:

• C1q knockout (KO) mice exhibited spontaneous and evoked epileptiform activity in neocortical slices.
• Increased excitatory synaptic connectivity (hotspot ratio) in layers IV and V of C1q KO mice.
• C1q KO mice displayed frequent behavioral seizures and increased axonal bouton density.

Conclusions:

• Genetic deficiency in C1q impairs neocortical synapse elimination.
• This failure in synaptic pruning leads to enhanced excitatory connectivity and epileptogenesis.
• C1q is essential for normal brain development and the prevention of epilepsy.