Poster Session 2 - B10
1,2Eric W Salter, 1,2Sun-Lim Choi, 1,2John Georgiou, 1,2Graham L Collingridge
1 Department of Physiology, University of Toronto; 2 Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, Toronto, ON, Canada.
Background: Aberrant activation of the complement cascade leads to synapse loss in Alzheimer’s disease models, and is implicated in the pathogenesis of schizophrenia. Neuronal activity is able to regulate complement activation and synapse pruning by microglia, however the precise activity patterns leading to complement activation are completely unknown. Studies have demonstrated that the complement cascade activates molecular pathways which are also involved in NMDAR-dependent long-term depression (NMDAR-LTD), suggesting that the complement cascade can regulate this form of synaptic plasticity. Hypothesis: The complement cascade is involved in the induction of NMDAR-LTD in the hippocampus. Methods: Using acute brain slice electrophysiology, we measured NMDAR-LTD in area CA1 from P13-P17 mice with a genetic deletion of either Cd11b or C3. Results: There was no difference in the magnitude of NMDAR-LTD induced by low-frequency stimulation in either male or female Cd11b-/- mice compared to littermate controls; metabotropic glutamate receptor (mGluR)-LTD was similarly unaltered. However, in female C3-/- mice, there was a significant reduction in the magnitude of NMDAR-LTD. Discussion: This study provides novel insights into the function of the complement cascade in the hippocampus, which suggests that complement component C3 is critical for the induction of NMDAR-LTD independent of the complement cascade. The knowledge gained in this study will be crucial for determining the precise role of this pathway in brain disorders including Alzheimer’s disease and schizophrenia.