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Post‐training, intrahippocampal HDAC inhibition differentially impacts neural circuits underlying spatial memory in adult and aged mice

Post‐training, intrahippocampal HDAC inhibition differentially impacts neural circuits underlying... ABSTRACT Converging evidence indicates that pharmacologically elevating histone acetylation using post‐training, systemic or intrahippocampal, administration of histone deacetylase inhibitor (HDACi) can enhance memory consolidation processes in young rodents but it is not yet clear, whether such treatment is sufficient to prevent memory impairments associated with aging. To address this question, we used a 1‐day massed spatial learning task in the water maze to investigate the effects of immediate post‐training injection of the HDACi trichostatin A (TSA) into the dorsal hippocampus on long‐term memory consolidation in 3–4 and 18–20 month‐old mice. We show that TSA improved the 24 h‐memory retention for the hidden platform location in young‐adults, but failed to rescue memory impairments in older mice. The results further indicate that Young‐TSA mice sacrificed 1 h after training had a robust increase in histone H4 acetylation in the dorsal hippocampal CA1 region (dCA1) and the dorsomedial part of the striatum (DMS), a structure important for spatial information processing. Importantly, TSA infusion in aged mice completely rescued altered H4 acetylation in the dCA1 but failed to alleviate age‐associated decreased H4 acetylation in the DMS. Moreover, intrahippocampal TSA infusion produced concomitant decreases (in adults) or increases (in older mice) of acetylated histone levels in the ventral hippocampus (vCA1 and vCA3) and the lateral amygdala, two structures critically involved in stress and emotional responses. These data suggest that the failure of post‐training, intrahippocampal TSA injection to reverse age‐associated memory impairments may be related to an inability to recruit appropriate circuit‐specific epigenetic patterns during early consolidation processes. © 2014 Wiley Periodicals, Inc. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Hippocampus Wiley

Post‐training, intrahippocampal HDAC inhibition differentially impacts neural circuits underlying spatial memory in adult and aged mice

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References (50)

Publisher
Wiley
Copyright
© 2015 Wiley Periodicals, Inc.
ISSN
1050-9631
eISSN
1098-1063
DOI
10.1002/hipo.22406
pmid
25530477
Publisher site
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Abstract

ABSTRACT Converging evidence indicates that pharmacologically elevating histone acetylation using post‐training, systemic or intrahippocampal, administration of histone deacetylase inhibitor (HDACi) can enhance memory consolidation processes in young rodents but it is not yet clear, whether such treatment is sufficient to prevent memory impairments associated with aging. To address this question, we used a 1‐day massed spatial learning task in the water maze to investigate the effects of immediate post‐training injection of the HDACi trichostatin A (TSA) into the dorsal hippocampus on long‐term memory consolidation in 3–4 and 18–20 month‐old mice. We show that TSA improved the 24 h‐memory retention for the hidden platform location in young‐adults, but failed to rescue memory impairments in older mice. The results further indicate that Young‐TSA mice sacrificed 1 h after training had a robust increase in histone H4 acetylation in the dorsal hippocampal CA1 region (dCA1) and the dorsomedial part of the striatum (DMS), a structure important for spatial information processing. Importantly, TSA infusion in aged mice completely rescued altered H4 acetylation in the dCA1 but failed to alleviate age‐associated decreased H4 acetylation in the DMS. Moreover, intrahippocampal TSA infusion produced concomitant decreases (in adults) or increases (in older mice) of acetylated histone levels in the ventral hippocampus (vCA1 and vCA3) and the lateral amygdala, two structures critically involved in stress and emotional responses. These data suggest that the failure of post‐training, intrahippocampal TSA injection to reverse age‐associated memory impairments may be related to an inability to recruit appropriate circuit‐specific epigenetic patterns during early consolidation processes. © 2014 Wiley Periodicals, Inc.

Journal

Hippocampus – Wiley

Published: Jul 1, 2015

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