Author Type

Graduate Student

Date of Award

Spring 4-29-2025

Document Type

Thesis

Publication Status

Version of Record

Submission Date

July 2026

College Granting Degree

Harriet L. Wilkes Honors College

Thesis/Dissertation Advisor [Chair]

Simon Pieraut

Abstract

This project examined C1q’s distribution in the extracellular matrix (ECM) and its specialized structures, perineuronal nets (PNNs), to explore the potential protective role the ECM plays against synaptic pruning. Traditionally, C1q deposits at weak synapses, initiating the complement cascade and signaling microglia to remove them. Preliminary data from the lab show that C1q accumulates in the ECM, suggesting a sequestering mechanism to protect synapses from C1q “tagging” and further elimination. In fact, initial observations indicate that most C1q clusters were not directly associated at the synapse. Using microscopy with fluorescent synaptic markers (Gephyrin-GFP, Homer-GFP), we assessed C1q’s spatial distribution relative to synaptic sites. To determine whether the ECM influences synapse tagging, we compared inhibitory parvalbumin (PV) neurons with and without PNNs to assess whether the presence of PNNs affect C1q tagging. This allowed us to evaluate whether PNNs offer an environment that protects synapses from C1q depositing. Ultimately, this study aimed to clarify C1q distribution in the ECM and whether PNNs modulate synapse regulation.

Download

Share

COinS