Abstract
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.
Highlights
Temporal lobe epilepsy (TLE) is characterized by recurrent seizures driven by synchronous neuronal activity
Mice were stereotactically injected in the dorsal dentate gyrus (DG) with a recombinant adeno-associated virus to express GCaMP6f in all granule cells (GCs)
The inverse relationship we find between seizure AUC and adult-born GC (abGC)-mGC synchrony is consistent with our finding that the two populations are significantly desynchronized in interictal epileptiform discharges (IEDs) in TLE compared to in sharp-wave ripples (SPW-Rs) in the nonepileptic animal (Fig. S4G)
Summary
Temporal lobe epilepsy (TLE) is characterized by recurrent seizures driven by synchronous neuronal activity. 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. Temporal lobe epilepsy (TLE) is a common neurological disorder characterized by recurrent focal seizures originating in the mesial temporal lobe, most commonly the hippocampus (HPC).
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