A central role for acetylcholine in entorhinal cortex function and dysfunction with age in humans and mice

2025/01/30 by Mala Ananth, John Gardus, Chuan Huang +7 · 1 voice
Neuroscience · #Memory and Neural Mechanisms #Sleep and Wakefulness Research #Neuroscience and Neuropharmacology Research

paper · doi:10.1016/j.celrep.2025.115249

openalex publication_date 2025/01/30 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/23

Abstract

Structural and functional changes in the entorhinal cortex (EC) are among the earliest signs of cognitive aging. Here, we ask whether a compromised cholinergic system influences early EC impairments and plays a primary role in EC cognition. We evaluated the relationship between loss of integrity of cholinergic inputs to the EC and cognitive deficits in otherwise healthy humans and mice. Using in vivo imaging (PET/MRI) in older humans and high-resolution imaging in wild-type mice and mice with genetic susceptibility to Alzheimer's disease pathology, we establish that loss of cholinergic input to the EC is, in fact, an early feature in cognitive aging. Through mechanistic studies in mice, we find a central role for EC-projecting cholinergic neurons in the expression of EC-related behaviors. Our data demonstrate that alterations to the cholinergic EC are an early, conserved feature of cognitive aging across species and may serve as an early predictor of cognitive status.

Citations

• Cholinergic innervation of cortex by the basal forebrain: Cytochemistry and cortical connections of the septal area, diagonal band nuclei, nucleus basalis (Substantia innominata), and hypothalamus in the rhesus monkey
• Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry
• The Montreal Cognitive Assessment, MoCA: A Brief Screening Tool For Mild Cognitive Impairment
• Entorhinal cortex dysfunction in Alzheimer's disease

Discussions

• A central role for acetylcholine in entorhinal cortex function and dysfunction with age in humans and mice: doi.org/10.1016/j.ce... PET/MRI in humans and IHC in an Alzheimer's mouse model showed a lo [bsky, 2 points, 0 comments]

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