Hippocampal adult-born granule cells drive network activity in a mouse model of chronic temporal lobe epilepsy

Temporal lobe epilepsy (TLE) is characterized by recurrent seizures driven by synchronous neuronal activity. The reorganization of the dentate gyrus (DG) in TLE may create pathological conduction pathways for synchronous discharges in the temporal lobe, though critical microcircuit-level detail is m...

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Bibliographic Details
Published in:Nature communications 2020-12, Vol.11 (1), p.6138-13, Article 6138
Main Authors: Sparks, F. T., Liao, Z., Li, W., Grosmark, A., Soltesz, I., Losonczy, A.
Format: Article
Language:English
Subjects:
14/63
14/69
631/378/1595/1554
631/378/1689/178
631/378/368/2431
Adult
Animals
Circuits
Convulsions & seizures
Dentate gyrus
Discharge
Disease Models, Animal
Electroencephalography
Epilepsy
Epilepsy, Temporal Lobe - physiopathology
Female
Firing pattern
Functional morphology
Granular materials
Granule cells
Hippocampus
Hippocampus - chemistry
Hippocampus - cytology
Hippocampus - physiopathology
Humanities and Social Sciences
Humans
Male
Mice
Mice, Inbred C57BL
multidisciplinary
Neurons - chemistry
Neurons - physiology
Science
Science (multidisciplinary)
Seizures
Synchronization
Temporal lobe
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Description
Summary:Temporal lobe epilepsy (TLE) is characterized by recurrent seizures driven by synchronous neuronal activity. The reorganization of the dentate gyrus (DG) in TLE may create pathological conduction pathways for synchronous discharges in the temporal lobe, though critical microcircuit-level detail is missing from this pathophysiological intuition. In particular, the relative contribution of adult-born (abGC) and mature (mGC) granule cells to epileptiform network events remains unknown. We assess dynamics of abGCs and mGCs during interictal epileptiform discharges (IEDs) in mice with TLE as well as sharp-wave ripples (SPW-Rs) in healthy mice, and find that abGCs and mGCs are desynchronized and differentially recruited by IEDs compared to SPW-Rs. We introduce a neural topic model to explain these observations, and find that epileptic DG networks organize into disjoint, cell-type specific pathological ensembles in which abGCs play an outsized role. Our results characterize identified GC subpopulation dynamics in TLE, and reveal a specific contribution of abGCs to IEDs. The dentate gyrus is involved in synchronous discharges and seizures, but its microcircuit functional organization in TLE is unclear. Here, the authors show that interictal discharges recruit specific granule cell ensembles dominated by adult-born immature neurons.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-020-19969-2