Reversing Aging: Decline in Complex Olfactory Learning Can be Rectified by Restoring Intrinsic Plasticity of Hippocampal CA1 Pyramidal Neurons

Richa Awasthi, Qi Yuan, Edi Barkai

Research output: Contribution to journalArticlepeer-review

Abstract

The acquisition of complex rules requires modifications in intrinsic plasticity of excitatory neurons within relevant brain areas. Olfactory discrimination (OD) rule learning occludes slow calcium-dependent potassium current (sIAHP) in piriform cortex (PC) pyramidal neurons, which increases their intrinsic neuronal excitability. Similar learning-induced sIAHP changes are demonstrated in hippocampal CA1. The shutdown of sIAHP is mediated by the metabotropic activation of the kainate subtype glutamatergic receptor, GluK2. Here, the duration of training required for OD rule learning increased significantly as the mice matured and aged is first shown, which appears earlier in 5xFAD mice. At the cellular biophysical level, aging is accompanied by reduction in the post-burst AHP in these neurons, while neuronal excitability remains stable. This is in contrast to aging CA1 neurons that exhibit enhanced post-burst AHPs in previous reports. Kainate reduces post-burst AHP in adults, but not in aged PC neurons, whereas it reduces post-burst AHPs in hippocampal CA1 pyramidal neurons of both young and aged mice. Overexpression of GluK2 in CA1 neurons restores OD learning capabilities in aged wild-type and 5xFAD mice, to a level comparable to young adults. Activation of GluK2 receptors in selectively vulnerable neurons can prevent aging-related cognitive decline is suggested.

Original languageEnglish
JournalAdvanced Biology
Early online date25 Dec 2023
DOIs
StateE-pub ahead of print - 25 Dec 2023

Bibliographical note

Publisher Copyright:
© 2023 The Authors. Advanced Biology published by Wiley-VCH GmbH.

Keywords

  • GluK2
  • afterhyperpolarization
  • aging
  • hippocampus
  • mouse
  • piriform cortex

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • Biomedical Engineering
  • Biomaterials

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