The Assay of Spatial Cognitive Deficit in Animal Models of Acquired or Genetic Encephalopathy
Abstract number :
3.049
Submission category :
1. Basic Mechanisms / 1E. Models
Year :
2021
Submission ID :
1826139
Source :
www.aesnet.org
Presentation date :
12/6/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:52 AM
Authors :
Jeremy Barry, PhD - Jeremy Barry;
Rationale: The connection between spatial cognitive deficits and the hyperarborization of dentate granule cells in both early-life seizure and autism spectrum disorder is currently unknown. As the dentate gyrus (DG) subfield is theorized to be important for both the gating of neocortical throughput in the hippocampus and the orthogonalization of hippocampal cell assemblies, DG hyperarborization and putative hyperexcitability should lead to spatial learning and memory impairments.
Methods: As a model of early-life seizure, Sprague-Dawley rat pups aged 10-11 days underwent procedures for experimental Febrile Status Epilepticus (eFSE) hyperthermia induction for 60 minutes. Following eFSE, animals and their normothermic but maternally deprived controls were returned to their dam to recover. For modeling autism spectrum disorder control and “Pten Floxed” mice are used. At P7, mice undergo 2 µl bilateral DG injections of replication-defective retroviruses based on pRubi. The pRubi injection has no effect on controls but knocks out Pten specifically in newborn granule neurons in Floxed mice.
Spatial cognition in both models is assessed using a dynamic spatial accuracy task. Animals are shaped to enter an 11 cm goal zone that is either marked by a bottle cap or needs to be located using distal spatial cues (egocentric vs. allocentric spatial tests). To trigger food reward, the animals must pause in the goal zone for 1.2 secs. The day after reaching criterion in the standard goal location, the cued goal zone is moved to a novel quadrant. In the following session, approximately 10 mins later, the session is re-run without the goal marker. The alternation of these visible and hidden goal cues is repeated in the remaining 2 quadrants on the following 2 days (Fig. 1).
Results: Pten ko mice perform as well as controls in the standard goal location for visible and hidden goal probe sessions, as well as the visible goal rotation sessions. However, Pten ko mice perform significantly worse than controls in the rotated hidden goal sessions (Fig. 2). Experiments with FSE and their normothermic controls are ongoing.
Conclusions: While further experimentation is necessary, the results suggest that hyperarborization of DG granule cell dendrites interferes with the association of recently visible object cues with a novel spatial location. The results have implications for novel treatment targets for acquired or genetic encephalopathy as well as for a mechanistic understanding of the role of the DG in spatial learning and memory.
Funding: Please list any funding that was received in support of this abstract.: NIH Grants NS108765 and NS108296 to JMB and GLH and R01MH097949 to B.W.L.
Basic Mechanisms