The effect of α7 containing nicotinic acetylcholine receptor knockout and PTZ induced seizure on immediate early gene expression in mouse brain
Graduation Year
2026
Document Type
Master's Thesis
Degree
Master of Science
Program
Biological Science
Partner Organization
BioMarin Phamaceuticals Inc.
Program Director
Patti Culross, MD, MPH
First Reader
Danielle Tan, PhD
Second Reader
George Bell
Abstract
Deletion of the α7 containing nicotinic acetylcholine receptor (α7*nAChR) has been associated with altered seizure susceptibility, yet its effects on activity-dependent transcriptional responses like the activation of immediate early genes (IEGs) following seizure remain incompletely characterized. In this study, we examined how α7*nAChR deletion influences IEG expression following chemically induced seizures using acute and chronic pentylenetetrazol (PTZ) administration in mice.
To spatially evaluate the transcriptional response of IEGs, we utilized a high-plex spatial transcriptomics assay on brain sections from wildtype, α7*nAChR heterozygous, and α7*nAChR knockout mice. This approach enabled detailed analysis of IEG expression across seizure paradigms and genotypes, with emphasis on hippocampal circuitry.
Acute seizure led to significant upregulation of Fos, Jun, and NUR77, while chronic seizure led to increased expression of Egr2 and Egr3, indicating engagement of distinct transcriptional programs following repeated seizure induction. Spatial analysis revealed seizure-associated niche-level reorganization within the dentate gyrus, characterized by reassignment of granule cells to a transcriptionally distinct cluster without disruption of anatomical organization.
Comparison between genotypes revealed α7*nAChR heterozygous and knockout animals exhibited increased seizure severity during acute PTZ exposure and trend toward altered transcriptional responses under seizure conditions. These findings suggest that α7*nAChR loss may modulate how hippocampal networks respond to seizure-induced activation.
Collectively, this work demonstrates that seizure induction engages spatially distinct, paradigm-dependent IEG programs within the hippocampus and that α7*nAChR deletion influences seizure susceptibility and transcriptional responses in a context-dependent manner.