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bioRxiv · 10.1101/2024.07.19.604332

Long-lived adult-born hippocampal neurons promote successful cognitive aging

Blin, N.·Charrier, V.·Farrugia, F.·Cartier, E.·Pacary, E.·Koehl, M.·Lois, C.·Lie, D. C.·Masachs, N.·Abrous, N.
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Abstract

Aging is commonly associated with a decline in memory abilities, yet some individuals remain resilient with preserved memory abilities. Memory processing is critically dependent on adult neurogenesis, a unique form of plasticity in the hippocampus. However, it remains unknown if cognitive aging influences the integration and role of adult-born hippocampal neurons (ABNs) generated early in adult life. Here, we investigated the role of long-lived ABNs in rats characterized as either resilient or vulnerable to cognitive aging using a peudo-longitudinal approach. Our findings reveal that long-lived ABNs support successful cognitive aging by preserving their synaptic inputs onto the proximal segments of their dendrites, and that these proximal synaptic sites also demonstrate a maintenance of their mitochondrial homeostasis. Furthermore, by-passing the reduced inputs of ABNs in vulnerable rats through direct optogenetic stimulation successfully improved their memory abilities. Overall, our data indicate that the maintenance of long-lived ABNs integration within the neuronal network is essential for successful cognitive aging, highlighting their potential as a therapeutic target for restoring cognitive functions in old age. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=141 SRC="FIGDIR/small/604332v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@524afforg.highwire.dtl.DTLVardef@b9b2b1org.highwire.dtl.DTLVardef@182a19corg.highwire.dtl.DTLVardef@1402b64_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Blin, N., Charrier, V., Farrugia, F., Cartier, E., Pacary, E., Koehl, M., Lois, C., Lie, D. C., Masachs, N., Abrous, N.. 2024-07-23. Long-lived adult-born hippocampal neurons promote successful cognitive aging. https://doi.org/10.1101/2024.07.19.604332

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