Targeting aberrant dendritic integration to treat cognitive comorbidities of epilepsy

Memory deficits are a debilitating symptom of epilepsy, but little is known about mechanisms underlying cognitive deficits. Here, we describe a Na+ channel-dependent mechanism underlying altered hippocampal dendritic integration, degraded place coding, and deficits in spatial memory. Two-photon glutamate uncaging experiments revealed that the mechanisms constraining the generation of Na+ spikes in hippocampal 1st order pyramidal cell dendrites are profoundly degraded in experimental epilepsy. This phenomenon was reversed by selectively blocking Nav1.3 sodium channels. In-vivo two-photon imaging revealed that hippocampal spatial representations were less precise in epileptic mice. Blocking Nav1.3 channels significantly improved the precision of spatial coding, and reversed hippocampal memory deficits. Thus, a dendritic channelopathy may underlie cognitive deficits in epilepsy and targeting it pharmacologically may constitute a new avenue to enhance cognition. One Sentence Summary Impaired input computations via aberrant dendritic spikes in chronic epilepsy degrade neuronal place codes and spatial memory

• Publication year

  2020

• Venue

  bioRxiv

• Publication date

  2020-11-23

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1101/2020.11.23.393694PMID 36448426PMCID 10232249
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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