Altered cognitive performance and synaptic function in the hippocampus of mice lacking C3

Area of Science:

• Neuroscience
• Immunology

Background:

• The complement system, particularly complement component 3 (C3), is implicated in synaptic elimination in the central nervous system (CNS).
• Its role in adult neurogenesis and cognitive functions remains incompletely understood.

Purpose of the Study:

• To investigate the function of the complement system in hippocampus-dependent learning and synaptic plasticity.
• To elucidate the specific role of C3 in cognitive performance and synaptic function.

Main Methods:

• Utilized C3-deficient mice to study learning and memory.
• Examined synaptic function at CA3-CA1 glutamatergic synapses.
• Assessed hippocampus-dependent learning, including place and reversal learning.

Main Results:

• Constitutive absence of C3 led to enhanced place and reversal learning in adult mice.
• C3 deficiency was associated with lower release probability at CA3-CA1 glutamatergic synapses.
• The overall efficacy of these synapses remained unaltered in C3-deficient mice, suggesting C3 negatively regulates the number of functional synapses.

Conclusions:

• C3 plays a critical role in regulating the number and function of hippocampal glutamatergic synapses.
• Absence of C3 positively impacts hippocampus-dependent cognitive performance.
• C3 acts as a negative regulator of cognitive functions mediated by the hippocampus.