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other·neurology, pediatrics, preclinical research, biomedical research·PMC10529121

Spatial learning impairments and discoordination of entorhinal-hippocampal circuit coding following prolonged febrile seizures

Hippocampus · 6 authors, 4 centres

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TL;DR

The central result was that eFSE induces a reorganization of synaptic inputs and diminished theta-gamma coupling in the entorhinal-hippocampal circuit, providing a physiological mechanism for spatial learning impairments.

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The authors report a reorganization of synaptic current sinks and sources along the CA1 and dentate gyrus (DG) somatodendritic axes in eFSE animals compared to controls. This included diminished theta-gamma amplitude-phase coupling at specific entorhinal synaptic inputs and altered intrahippocampal phase coordination. For example, current source density levels in the medial molecular layer of the dentate gyrus had predictive power regarding the severity of cognitive deficits.

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other

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neurology

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ORIGINAL PAPER

PMC10529121

Spatial learning impairments and discoordination of entorhinal-hippocampal circuit coding following prolonged febrile seizures

Hippocampus

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ABSTRACT

Abstract How the development and function of neural circuits governing learning and memory are affected by insults in early life remains poorly understood. The goal of this study was to identify putative changes in cortico-hippocampal signaling mechanisms that could lead to learning and memory deficits in a clinically relevant developmental pathophysiological rodent model, Febrile status epilepticus (FSE). FSE in both pediatric cases and the experimental animal model, is associated with enduring physiological alterations of the hippocampal circuit and cognitive impairment. Here, we deconstruct hippocampal circuit throughput by inducing slow theta oscillations in rats under urethane anesthesia and isolating the dendritic compartments of CA1 and dentate gyrus subfields, their reception of medial and lateral entorhinal cortex inputs, and the efficacy of signal propagation to each somatic cell layer. We identify FSE-induced theta-gamma decoupling at cortical synaptic input pathways and altered signal phase coherence along the CA1 and dentate gyrus somatodendritic axes. Moreover, increased DG synaptic activity levels are predictive of poor cognitive outcomes. We propose that these alterations in cortico-hippocampal coordination interfere with the ability of hippocampal dendrites to receive, decode and propagate neocortical inputs. If this frequency-specific syntax is necessary for cortico-hippocampal coordination and spatial learning and memory, its loss could be a mechanism for FSE cognitive comorbidities. Keywords: circuit throughput, development, febrile status epilepticus, network development, pathology, seizures, spatial memory

CITATION EXPORT

Michelle L Kloc, Yuncai Chen, Jennifer M Daglian et al.. Spatial learning impairments and discoordination of entorhinal-hippocampal circuit coding following prolonged febrile seizures. Hippocampus. (2023). https://doi.org/10.1002/hipo.23541

AUTHORS

6 · 4 CENTRES

Michelle L Kloc, Yuncai Chen, Jennifer M Daglian, Gregory L Holmes, Tallie Z Baram, Jeremy M Barry

1Epilepsy Cognition and Development Group, Department of Neurological Sciences, University of Vermont, Larner College of Medicine, Burlington, Vermont, USA
2Departments of Pediatrics, University California-Irvine, Irvine, California, USA
3Departments of Anatomy/Neurobiology, University California-Irvine, Irvine, California, USA
4Departments of Neurology, University California-Irvine, Irvine, California, USA