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

Area of Science:

• Neuroscience
• Aging Research
• Cognitive Science

Background:

• Structural and functional changes in the entorhinal cortex (EC) are early indicators of cognitive aging.
• The role of the cholinergic system in early EC impairments and cognition is not fully understood.

Purpose of the Study:

• To investigate the relationship between cholinergic input integrity and cognitive deficits in aging humans and mice.
• To determine if compromised cholinergic systems are a primary driver of early entorhinal cortex impairments.

Main Methods:

• Utilized in vivo imaging techniques including Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) in older humans.
• Employed high-resolution imaging in wild-type mice and mice genetically susceptible to Alzheimer's disease pathology.
• Conducted mechanistic studies in mice to assess the role of EC-projecting cholinergic neurons in behavior.

Main Results:

• Loss of cholinergic input to the entorhinal cortex (EC) is an early feature of cognitive aging, observed in both humans and mice.
• Mechanistic studies in mice revealed a central role for EC-projecting cholinergic neurons in EC-related behaviors.
• Alterations in the cholinergic EC are conserved across species and appear early in the aging process.

Conclusions:

• Compromised cholinergic input to the entorhinal cortex (EC) is an early and conserved feature of cognitive aging.
• Loss of cholinergic integrity in the EC may serve as an early predictor of cognitive status.
• Targeting the cholinergic system in the EC could be a potential strategy for mitigating age-related cognitive decline.