Different subsets of newborn granule cells: a possible role in epileptogenesis?

Abstract

Several factors, including epileptic seizures, can strongly stimulate ongoing neurogenesis in the adult hippocampus. Although adult-born granule cells generated after seizure activity have different physiological properties from their normal counterparts, they integrate into the existing, mature network of the adult hippocampal dentate gyrus. However, the exact role of the neurogenic response during epilepsy and its possible involvement in epileptogenesis have remained elusive. Here, we discuss recent studies shedding new light on the interplay between epilepsy and neurogenesis, and try to explain discrepancies in this literature by proposing seizure severity-dependent induction of two subsets of newborn cells with different properties. We hypothesise that a low seizure intensity would stimulate neurogenesis to a 'physiological plasticity' level and have few pathological consequences. In contrast, a high initial seizure intensity may induce a specific subset of altered and/or ectopically located new granule cells with different electrophysiological properties that could initiate hyperexcitatory recurrent networks that could, in turn, contribute to chronic epilepsy. This hypothesis may clarify previously contradictory data in the literature, and could thereby aid in our understanding of the role of neurogenesis in epileptogenesis, and open up promising avenues for therapeutic intervention.

Neural Circuits Underlying Visually Evoked Escapes in Larval Zebrafish

“…While studies of escape behaviors have often focused on impulse-like mechanosensory stimulation such as a touch or brief auditory buzz, where stimulus control and behavioral execution is straightforward and where the underlying sensory detection and processing pathways are relatively compact. The visual system, however, is arguably better suited for detecting threatening stimuli, as visual cues can be detected long before the mechanical signatures of an approaching predator reach somatosensory and auditory systems (Billington et al, 2011; Fotowat et al, 2011; Khakhalin et al, 2014; Oliva et al, 2007; Preuss et al, 2006; Yilmaz and Meister, 2013). At the same time, the sensory computations required for the visual detection of threats are potentially more complex, as these must involve the rapid analysis of high-dimensional spatiotemporal sensory streams.…”

Role of fractalkine–CX3CR1 pathway in seizure-induced microglial activation, neurodegeneration, and neuroblast production in the adult rat brain

“…The function of new neurons in a seizure-environment may, however, be different from physiological conditions, though previous observations from new seizure-induced neurons remaining within the granule cell layer (GCL) of the dentate gyrus have suggested that they may counteract hyperexcitability (Jakubs et al, 2006;Jackson et al, 2012). Conversely, following more severe seizures, some new neurons migrate aberrantly into the dentate hilus and there they may instead propagate excitability (Parent et al, 1997;Scharfman et al, 2000;Parent and Lowenstein, 2002;Bielefeld et al, 2014). The role of inflammation for these aberrant neurons remains unclear.…”

Reduced abnormal integration of adult-generated granule cells does not attenuate spontaneous recurrent seizures in mice

“…Once status epilepticus began (defined by continuous tonic clonic convulsive seizures), mice were housed at room temperature and returned to an incubator after seizure activity stopped. Because low seizure intensity would stimulate neurogenesis to a 'physiological plasticity' level and have few pathological consequences (for review, see Bielefeld et al, 2014), which may affect the results of the current experiment, diazepam was not used to stop seizure activities after several hours of the SE. The latency (between pilocarpine injection and the occurrence of status epilepticus), maintenance time (from beginning to the end of status epilepticus) and the number of stage 5 seizures (rearing and falling with forelimb clonus) were recorded (Racine, 1972).…”

“…However, given the fact that reactive gliosis in epilepsy partially facilitate epileptogenesis (Gibbons et al, 2013;Vezzani et al, 2015), unchanged SRSs in this study hence cannot be attributed to possible decrease of reactive gliosis. Moreover, we cannot assume that all newborn granule cells with abnormal integrations are culprits (for review, see Bielefeld et al, 2014). According to the findings of Murphy et al (2011), when some of newborn granule cells exhibited reductions in dendritic spine number suggesting reduced excitatory input to these cells, the others have large numbers of spines and long basal dendrites, indicating robustly integrations into the pathological circuitry of the epileptic brain.…”