Distinct Roles of mTORC1 and mTORC2 in Regulating Inhibitory Synaptic Input After Status Epilepticus
Abstract number :
1.005
Submission category :
1. Basic Mechanisms / 1A. Epileptogenesis of acquired epilepsies
Year :
2025
Submission ID :
1096
Source :
www.aesnet.org
Presentation date :
12/6/2025 12:00:00 AM
Published date :
Authors :
Presenting Author: Sarah Yaser, BA Neuroscience – University of Cincinnati College of Medicine
Christin Godale, PhD – University of Cincinnati College of Medicine
Austin Drake, PhD – University of Cincinnati
Kimberly Kraus, MD, PhD – University of Cincinnati College of Medicine
Natasha Mayer, BS – University of Cincinnati College of Medicine
Mary Dusing, BS – Cincinnati Children's Hospital Medical Center
Candi LaSarge, PhD – Cincinnati Children's Hospital Medical Center
Christina Gross, PhD – Cincinnati Children's Hospital Medical Center
Steve Danzer, PhD – Cincinnati Children's Hospital Medical Center
Rationale: mTOR signaling through mTORC1 (Raptor-dependent) and mTORC2 (Rictor-dependent) pathways regulates neuronal morphology and excitability. Dysregulated mTOR signaling is implicated in epileptogenesis, with both excitatory and inhibitory circuit remodeling observed. While global deletion of Raptor or Rictor can reduce seizure incidence in different models, how these deletions affect inhibitory innervation, particularly perisomatic input from parvalbumin-positive (PV+) interneurons, is unclear. Given that PV+ basket cells mediate critical perisomatic inhibition of dentate granule cells (DGCs), we investigated how conditional, cell-autonomous deletion of Raptor or Rictor from DGCs influences PV-mediated inhibitory synaptic input after status epilepticus (SE).
Methods: Raptorfl/fl or Rictorfl/fl mice carrying a tdTomato reporter underwent pilocarpine-induced SE or saline treatment. One week later, bilateral hippocampal injections of AAV9.CamKII.eGFP and AAV9.CamKII.Cre produced GFP+ wild-type and tdTomato+ knockout DGCs. Two months post-injection, immunohistochemistry for PV (presynaptic marker) and gephyrin (postsynaptic inhibitory marker) was performed. Super-resolution confocal imaging (Nikon AXR NSPARC, 100x, 0.086 μm/pixel) enabled quantification of puncta per µm along the soma perimeter and the percentage of the soma perimeter apposed to puncta of each type.
Results: Parvalbumin puncta density was unaffected by SE or genotype across all groups. However, gephyrin puncta density was significantly reduced by SE in control mice (p < 0.001), but not in Raptor or Rictor knockouts. Similarly, PV puncta
Basic Mechanisms