Microglia refine early multisensory circuits in the lateral cortex of the inferior colliculus in a complement-dependent manner

Author

Shaida Hamidi, James Madison UniversityFollow

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Date of Graduation

5-11-2023

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Department of Biology

Advisor(s)

Mark Gabriele

Ray Enke

George Vidal

Abstract

Microglia cells (MGCs), the resident macrophage of the brain, play a pivotal role in synaptic pruning of newly established circuits during early critical periods. Classical complement cascade signaling enables MGCs to identify unnecessary or underutilized contacts and specifically target them for removal and subsequent degradation. Such recognition and engulfment behaviors require receptor-ligand interactions, whereby “eat me” tags (complement component 3, C3) bind their cognate receptor (complement receptor 3, CR3) expressed on MGCs. Compromised complement signaling in certain systems results in under-pruning or unrefined map configurations, and is thought perhaps to underlie certain autism-related behavioral phenotypes (e.g. sensory hypersensitivities, decreased social interaction, increased repetitive behaviors). The lateral cortex of the inferior colliculus (LCIC) is a compartmentalized midbrain center that receives segregated inputs from multiple sensory modalities. Somatosensory afferents target a series of modular domains, while auditory afferents terminate throughout an encompassing matrix. Despite the fact that multisensory processing deficits are among the most reliable early indicators and severity predictors of autistic symptoms, the role of MGCs and complement signaling in sculpting multisensory circuits has yet to be addressed. Thus, the goal of the present study is to determine whether classical complement cascade signaling may be influential in MGC-mediated pruning of early LCIC multisensory circuits. A developmental series of postnatal GAD67-GFP knock-in and CR3KO mice were utilized to (1) characterize the time course of C3 expression in the developing LCIC, (2) correlate CR3/CD11b-positive MGC patterns with any observed changes in C3 staining, and (3) determine if mice incapable of complement signaling (CR3KO) exhibit any abnormalities in the described expression patterns. Results indicate C3 expression is cleared in a compartmental-specific manner (i.e. modules first, then matrix), that CD11b-expressing MGCs correlate spatially and temporally with such observations, and that compromised complement signaling results in a delay in C3 clearance from the LCIC until after its critical period closure. These findings implicate MGCs as potential key players in sculpting early LCIC circuits and that deficits in complement pathway signaling may yield unrefined multisensory network maps.

Recommended Citation

Hamidi, Shaida, "Microglia refine early multisensory circuits in the lateral cortex of the inferior colliculus in a complement-dependent manner" (2023). Masters Theses, 2020-current. 244.
https://commons.lib.jmu.edu/masters202029/244