Adult-born neurons maintain hippocampal cholinergic inputs and support working memory during aging

Area of Science:

• Neuroscience
• Cognitive Science
• Aging Research

Background:

• Adult neurogenesis, the birth of new neurons in the adult brain, is crucial for hippocampal function.
• Reduced neurogenesis is linked to aging, stress, and cognitive disorders, but its precise role in brain function is unclear.
• A systems-level understanding of how new neurons impact overall brain function, particularly memory, is lacking.

Approach:

• Investigated the role of adult neurogenesis in maintaining hippocampal connections over a lifetime.
• Examined the effects of long-term neurogenesis suppression on acetylcholine signaling and working memory.
• Analyzed compensatory reorganization within the cholinergic system in response to neurogenesis deficits.

Key Points:

• Long-term suppression of adult neurogenesis mimics aging and stress, leading to faster decline in hippocampal acetylcholine signaling.
• Working memory deficits emerged progressively with neurogenesis suppression, accompanied by compensatory changes in cholinergic pathways.
• Despite initial dysfunction, compensatory cholinergic innervation could be recruited to improve memory, even in aged animals.

Conclusions:

• Adult neurogenesis is vital for sustaining the septohippocampal cholinergic circuit throughout life, thereby supporting memory function.
• This study offers a systems-level explanation for progressive memory deterioration in aging and pathological conditions.
• Demonstrates the brain's plasticity and the malleability of the connectome by experience, highlighting neurogenesis as a key factor.