Neurogenesis Dynamics in Temporal Lobe Epilepsy

Temporal lobe epilepsy (TLE) is characterised by recurrent seizures originating in hippocampal circuits, notably the dentate gyrus. A hallmark of TLE is altered adult hippocampal neurogenesis, in which new granule cells born in the subgranular zone display atypical migration, dendritic architecture and synaptic integration. These aberrant neurons can form recurrent excitatory loops—through mechanisms such as mossy fibre sprouting and ectopic cell placement—thereby exacerbating network hyperexcitability. Timing of cell birth relative to the epileptogenic insult is critical: granule cells generated during a defined post-insult window often mature abnormally and promote seizures, whereas earlier-born cohorts may integrate more normally. Concurrently, excessive neuronal activity depletes neural stem cell pools and impairs long-term cognitive functions such as pattern separation. Modulating neurogenic dynamics has emerged as a promising strategy to reduce seizure burden and preserve memory, underscoring the translational potential of targeting adult neurogenesis in TLE.

Research from Nature Portfolio

Foundational work demonstrated that selective ablation of adult hippocampal neurogenesis before an epileptogenic insult yields durable suppression of spontaneous recurrent seizures and reverses associated memory deficits, firmly establishing a causal role for adult-born granule cells in epileptogenesis. Subsequent studies have defined a critical post-insult window in which aberrant newborn granule cells exhibit abnormal dendritic branching and ectopic migration; silencing these cells during that period restores proper network connectivity, diminishes recurrent CA3 back-projections and reduces seizure susceptibility. More recent investigations using neuronal ensemble analysis have shown that, during interictal epileptiform discharges, adult-born and mature granule cells segregate into distinct pathological ensembles, with newborn neurons disproportionately driving aberrant network activity. These insights elucidate how disrupted integration of adult-born granule cells rewires hippocampal microcircuits to fuel epilepsy and pinpoint cell-type-specific targets for intervention.

Neurogenesis Dynamics in Temporal Lobe Epilepsy publication trend

The graph below shows the total number of articles in neurogenesis dynamics in temporal lobe epilepsy across all publications each year (not limited to Nature Index journals).

Technical terms

Adult-born granule cells (abGCs): Neurons generated postnatally in the hippocampal dentate gyrus that integrate into existing circuits.

Aberrant neurogenesis: Disordered generation, migration or synaptic incorporation of new neurons leading to atypical circuitry.

Interictal epileptiform discharges (IEDs): Brief, abnormal electrical events in hippocampal networks occurring between seizures.

Mossy fibre sprouting: Growth of dentate granule cell axons into the inner molecular layer, forming recurrent excitatory loops.

Pattern separation: Process by which the dentate gyrus distinguishes similar inputs to support memory encoding.

References

1. Adult-born neurons in critical period maintain hippocampal seizures via local aberrant excitatory circuits. Signal Transduction and Targeted Therapy (2023).
2. Single-cell, single-nucleus and xenium-based spatial transcriptomics analyses reveal inflammatory activation and altered cell interactions in the hippocampus in mice with temporal lobe epilepsy. Biomarker Research (2024).
3. Increasing adult-born neurons protects mice from epilepsy. eLife (2024).
4. Seizure-induced LIN28A disrupts pattern separation via aberrant hippocampal neurogenesis. JCI Insight (2024).
5. Neuronal Hyperactivity Accelerates Depletion of Neural Stem Cells and Impairs Hippocampal Neurogenesis. Cell Stem Cell (2015).
6. Aberrant hippocampal neurogenesis contributes to epilepsy and associated cognitive decline. Nature Communications (2015).
7. A critical period of neuronal activity results in aberrant neurogenesis rewiring hippocampal circuitry in a mouse model of epilepsy. Nature Communications (2021).
8. Hippocampal adult-born granule cells drive network activity in a mouse model of chronic temporal lobe epilepsy. Nature Communications (2020).