Hippocampal adult-born granule cells drive network activity in a mouse model of chronic temporal lobe epilepsy.
Fraser T SparksZ LiaoW LiA GrosmarkIvan SolteszAttila LosonczyPublished in: Nature communications (2020)
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.
Keyphrases
- temporal lobe epilepsy
- induced apoptosis
- mouse model
- cell cycle arrest
- high fat diet induced
- oxidative stress
- gestational age
- signaling pathway
- endoplasmic reticulum stress
- type diabetes
- cell death
- high resolution
- metabolic syndrome
- pi k akt
- brain injury
- dna methylation
- subarachnoid hemorrhage
- wild type
- solid phase extraction