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Cognitive aging is associated with redistribution of synaptic weights in the hippocampus.

ABSTRACT: Behaviors that rely on the hippocampus are particularly susceptible to chronological aging, with many aged animals (including humans) maintaining cognition at a young adult-like level, but many others the same age showing marked impairments. It is unclear whether the ability to maintain cognition over time is attributable to brain maintenance, sufficient cognitive reserve, compensatory changes in network function, or some combination thereof. While network dysfunction within the hippocampal circuit of aged, learning-impaired animals is well-documented, its neurobiological substrates remain elusive. Here we show that the synaptic architecture of hippocampal regions CA1 and CA3 is maintained in a young adult-like state in aged rats that performed comparably to their young adult counterparts in both trace eyeblink conditioning and Morris water maze learning. In contrast, among learning-impaired, but equally aged rats, we found that a redistribution of synaptic weights amplifies the influence of autoassociational connections among CA3 pyramidal neurons, yet reduces the synaptic input onto these same neurons from the dentate gyrus. Notably, synapses within hippocampal region CA1 showed no group differences regardless of cognitive ability. Taking the data together, we find the imbalanced synaptic weights within hippocampal CA3 provide a substrate that can explain the abnormal firing characteristics of both CA3 and CA1 pyramidal neurons in aged, learning-impaired rats. Furthermore, our work provides some clarity with regard to how some animals cognitively age successfully, while others' lifespans outlast their "mindspans."

SUBMITTER: Buss EW

PROVIDER: S-EPMC7923642 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Cognitive aging is associated with redistribution of synaptic weights in the hippocampus.

Buss Eric W EW Corbett Nicola J NJ Roberts Joshua G JG Ybarra Natividad N Musial Timothy F TF Simkin Dina D Molina-Campos Elizabeth E Oh Kwang-Jin KJ Nielsen Lauren L LL Ayala Gelique D GD Mullen Sheila A SA Farooqi Anise K AK D'Souza Gary X GX Hill Corinne L CL Bean Linda A LA Rogalsky Annalise E AE Russo Matthew L ML Curlik Dani M DM Antion Marci D MD Weiss Craig C Chetkovich Dane M DM Oh M Matthew MM Disterhoft John F JF Nicholson Daniel A DA

Proceedings of the National Academy of Sciences of the United States of America 20210201 8

Behaviors that rely on the hippocampus are particularly susceptible to chronological aging, with many aged animals (including humans) maintaining cognition at a young adult-like level, but many others the same age showing marked impairments. It is unclear whether the ability to maintain cognition over time is attributable to brain maintenance, sufficient cognitive reserve, compensatory changes in network function, or some combination thereof. While network dysfunction within the hippocampal circ ...[more]

PMID: 33593893

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Dataset Information

Cognitive aging is associated with redistribution of synaptic weights in the hippocampus.

Publications

Cognitive aging is associated with redistribution of synaptic weights in the hippocampus.

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