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Fear extinction is impaired in aged rats

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Abstract

Normal aging is accompanied by broad loss of cognitive function in humans and rodents, including declines in cognitive flexibility. In extinction, a conditional stimulus (CS) that was previously paired with a footshock is presented alone. This procedure reliably reduces conditional freezing behavior in young adult rats. Here, we aimed to investigate how normal aging affects extinction learning. Using young (3 months) and aged (20 months) male and female Long Evans rats, we compared extinction (using 20 CS-alone presentations) to a no extinction control (equal exposure to the conditioning chamber without CS presentations) following delay fear conditioning. We found that young animals in the extinction group showed a decrease in freezing following extinction; aged animals did not. We next examined changes in neural activity using expression of the immediate early gene zif268. In young animals, extinction corresponded with decreased expression of zif268 in the basolateral amygdala and anterior retrosplenial cortex; this was not observed in aged animals. Further, aged animals showed increased zif268 expression in each region examined, suggesting that dysfunction in neural activity precedes cognitive deficits. These results demonstrate that aging impacts both extinction learning and neural activity.

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Acknowledgements

We thank the animal care staff in the Purdue University Department of Psychological Sciences for providing care for the rats used in this study and Dr. Nicole Ferrara for input on conceptualization of the experiment.

Funding

This work was supported by the Research Corporation for Science Advancement (Award No. 29107) to S.T.

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Authors and Affiliations

  1. Department of Psychological Sciences, Purdue University, West Lafayette, IN, 47907, USA

    Payton K. Robinson, Erisa Met Hoxha, Destine Williams, Kimberly P. Kinzig & Sydney Trask

  2. Institute for Integrative Neuroscience, Purdue University, West Lafayette, IN, 47907, USA

    Kimberly P. Kinzig & Sydney Trask

  3. Center On Aging and the Life Course, Purdue University, West Lafayette, IN, 47907, USA

    Sydney Trask

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  1. Payton K. Robinson
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  2. Erisa Met Hoxha
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  3. Destine Williams
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  5. Sydney Trask
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Contributions

P.K.R., E.M., and S.T. designed the experiments. P.K.R., E.M., D.W., and S.T. performed the data collection. P.K.R., E.M., K.P.K., and S.T. wrote the manuscript.

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Correspondence to Sydney Trask.

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Robinson, P.K., Met Hoxha, E., Williams, D. et al. Fear extinction is impaired in aged rats. GeroScience 46, 2815–2825 (2024). https://doi.org/10.1007/s11357-024-01084-5

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