Title : Deficits in behavioral and neuronal pattern separation in temporal lobe epilepsy
In temporal lobe epilepsy, the ability of the dentate gyrus to limit excitatory cortical input to the hippocampus breaks down, leading to seizures. The dentate gyrus is also thought to help discriminate between similar memories by performing pattern separation, but whether epilepsy leads to a breakdown in this neural computation, and thus to mnemonic discrimination impairments, remains unknown. Here we show that temporal lobe epilepsy is characterized by behavioral deficits in mnemonic discrimination tasks, in both humans (females and males) and mice (C57Bl6 males, systemic low dose kainate model). Using a recently developed assay in brain slices of the same epileptic mice, we reveal a decreased ability of the dentate gyrus to perform certain forms of pattern separation. This is because of a subset of granule cells with abnormal bursting that can develop independently of early EEG abnormalities. Overall, our results linking physiology, computation, and cognition in the same mice advance our understanding of episodic memory mechanisms and their dysfunction in epilepsy.
Audience Take Away
- Most temporal lobe epilepsy-related dentate gyrus pathologies have been investigated on a computational model, this paper provides experimental evidence that temporal lobe epilepsy is characterized by impairments in mnemonic discrimination and neuronal pattern separation deficits
- We found a deficit that is not as large as many previously studied models, therefore introducing a possibility of plasticity’s role in functional regain. This can help during treatment plans for patients recovering from temporal lobe epilepsy and subsequent dentate gyrus related memory consolidation problems
- This is research that needs expanding upon as this is a primary study establishing the mnemonic and spatial related memory problems that arise secondary to temporal lobe epilepsy. Expansion particularly in different testing models, treatment options and early diagnostic tools
- In this paper it is found that there is a subset of granule cells with pattern separation deficits which can develop without EEG hallmarks of epilepsy. Therefor this is an early mechanism of impairment in electrogenesis. This information is valuable in the future of research
- Additionally, we have improved and expanded upon existing pattern separation protocols on the mouse model