Missing Puzzle Pieces in Dementia Research: HCN Channels and Theta Oscillations

Aging Dis. 2024 Feb 1;15(1):22-42. doi: 10.14336/AD.2023.0607.

Abstract

Increasing evidence indicates a role of hyperpolarization activated cation (HCN) channels in controlling the resting membrane potential, pacemaker activity, memory formation, sleep, and arousal. Their disfunction may be associated with the development of epilepsy and age-related memory decline. Neuronal hyperexcitability involved in epileptogenesis and EEG desynchronization occur in the course of dementia in human Alzheimer's Disease (AD) and animal models, nevertheless the underlying ionic and cellular mechanisms of these effects are not well understood. Some suggest that theta rhythms involved in memory formation could be used as a marker of memory disturbances in the course of neurogenerative diseases, including AD. This review focusses on the interplay between hyperpolarization HCN channels, theta oscillations, memory formation and their role(s) in dementias, including AD. While individually, each of these factors have been linked to each other with strong supportive evidence, we hope here to expand this linkage to a more inclusive picture. Thus, HCN channels could provide a molecular target for developing new therapeutic agents for preventing and/or treating dementia.

Publication types

  • Review

MeSH terms

  • Animals
  • Dementia*
  • Epilepsy*
  • Humans
  • Membrane Potentials / physiology
  • Nervous System Physiological Phenomena*

Grants and funding

We thank Dr Marcin Siwiec from Maj Institute of Pharmacology Polish Academy of Sciences in Krakow for insightful comments. The publication of this article was made possible by National Science Centre, Poland Grant No. 2017/26/D/NZ4/00159. Views expressed herein are those of the authors. The funding sources played no role in the preparation of this manuscript.