Age-related differences in affective behaviors in mice: possible role of prefrontal cortical-hippocampal functional connectivity and metabolomic profiles

IntroductionThe differential expression of emotional reactivity from early to late adulthood may involve maturation of prefrontal cortical responses to negative valence stimuli. In mice, age-related changes in affective behaviors have been reported, but the functional neural circuitry warrants furth...

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Main Authors: Marcelo Febo, Rohit Mahar, Nicholas A. Rodriguez, Joy Buraima, Marjory Pompilus, Aeja M. Pinto, Matteo M. Grudny, Adriaan W. Bruijnzeel, Matthew E. Merritt
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-03-01
Series:Frontiers in Aging Neuroscience
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Online Access:https://www.frontiersin.org/articles/10.3389/fnagi.2024.1356086/full
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author Marcelo Febo
Rohit Mahar
Nicholas A. Rodriguez
Joy Buraima
Marjory Pompilus
Aeja M. Pinto
Matteo M. Grudny
Adriaan W. Bruijnzeel
Matthew E. Merritt
author_facet Marcelo Febo
Rohit Mahar
Nicholas A. Rodriguez
Joy Buraima
Marjory Pompilus
Aeja M. Pinto
Matteo M. Grudny
Adriaan W. Bruijnzeel
Matthew E. Merritt
author_sort Marcelo Febo
collection DOAJ
description IntroductionThe differential expression of emotional reactivity from early to late adulthood may involve maturation of prefrontal cortical responses to negative valence stimuli. In mice, age-related changes in affective behaviors have been reported, but the functional neural circuitry warrants further investigation.MethodsWe assessed age variations in affective behaviors and functional connectivity in male and female C57BL6/J mice. Mice aged 10, 30 and 60 weeks (wo) were tested over 8 weeks for open field activity, sucrose preference, social interactions, fear conditioning, and functional neuroimaging. Prefrontal cortical and hippocampal tissues were excised for metabolomics.ResultsOur results indicate that young and old mice differ significantly in affective behavioral, functional connectome and prefrontal cortical-hippocampal metabolome. Young mice show a greater responsivity to novel environmental and social stimuli compared to older mice. Conversely, late middle-aged mice (60wo group) display variable patterns of fear conditioning and during re-testing in a modified context. Functional connectivity between a temporal cortical/auditory cortex network and subregions of the anterior cingulate cortex and ventral hippocampus, and a greater network modularity and assortative mixing of nodes was stronger in young versus older adult mice. Metabolome analyses identified differences in several essential amino acids between 10wo mice and the other age groups.DiscussionThe results support differential expression of ‘emotionality’ across distinct stages of the mouse lifespan involving greater prefrontal-hippocampal connectivity and neurochemistry.
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spelling doaj.art-4f0f9079ac464cad8527bfce8c8840ff2024-03-08T04:32:26ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652024-03-011610.3389/fnagi.2024.13560861356086Age-related differences in affective behaviors in mice: possible role of prefrontal cortical-hippocampal functional connectivity and metabolomic profilesMarcelo Febo0Rohit Mahar1Nicholas A. Rodriguez2Joy Buraima3Marjory Pompilus4Aeja M. Pinto5Matteo M. Grudny6Adriaan W. Bruijnzeel7Matthew E. Merritt8Department of Psychiatry, McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL, United StatesDepartment of Chemistry, Hemvati Nandan Bahuguna Garhwal University (A Central University), Srinagar Garhwal, Uttarakhand, IndiaDepartment of Psychiatry, McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL, United StatesDepartment of Psychiatry, McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL, United StatesDepartment of Psychiatry, McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL, United StatesDepartment of Psychiatry, McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL, United StatesDepartment of Psychiatry, McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL, United StatesDepartment of Psychiatry, McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL, United StatesDepartment of Biochemistry and Molecular Biology, University of Florida College of Medicine, Gainesville, FL, United StatesIntroductionThe differential expression of emotional reactivity from early to late adulthood may involve maturation of prefrontal cortical responses to negative valence stimuli. In mice, age-related changes in affective behaviors have been reported, but the functional neural circuitry warrants further investigation.MethodsWe assessed age variations in affective behaviors and functional connectivity in male and female C57BL6/J mice. Mice aged 10, 30 and 60 weeks (wo) were tested over 8 weeks for open field activity, sucrose preference, social interactions, fear conditioning, and functional neuroimaging. Prefrontal cortical and hippocampal tissues were excised for metabolomics.ResultsOur results indicate that young and old mice differ significantly in affective behavioral, functional connectome and prefrontal cortical-hippocampal metabolome. Young mice show a greater responsivity to novel environmental and social stimuli compared to older mice. Conversely, late middle-aged mice (60wo group) display variable patterns of fear conditioning and during re-testing in a modified context. Functional connectivity between a temporal cortical/auditory cortex network and subregions of the anterior cingulate cortex and ventral hippocampus, and a greater network modularity and assortative mixing of nodes was stronger in young versus older adult mice. Metabolome analyses identified differences in several essential amino acids between 10wo mice and the other age groups.DiscussionThe results support differential expression of ‘emotionality’ across distinct stages of the mouse lifespan involving greater prefrontal-hippocampal connectivity and neurochemistry.https://www.frontiersin.org/articles/10.3389/fnagi.2024.1356086/fullagingbrain maturationfMRIfear conditioninglocomotor activityfunctional connectivity
spellingShingle Marcelo Febo
Rohit Mahar
Nicholas A. Rodriguez
Joy Buraima
Marjory Pompilus
Aeja M. Pinto
Matteo M. Grudny
Adriaan W. Bruijnzeel
Matthew E. Merritt
Age-related differences in affective behaviors in mice: possible role of prefrontal cortical-hippocampal functional connectivity and metabolomic profiles
Frontiers in Aging Neuroscience
aging
brain maturation
fMRI
fear conditioning
locomotor activity
functional connectivity
title Age-related differences in affective behaviors in mice: possible role of prefrontal cortical-hippocampal functional connectivity and metabolomic profiles
title_full Age-related differences in affective behaviors in mice: possible role of prefrontal cortical-hippocampal functional connectivity and metabolomic profiles
title_fullStr Age-related differences in affective behaviors in mice: possible role of prefrontal cortical-hippocampal functional connectivity and metabolomic profiles
title_full_unstemmed Age-related differences in affective behaviors in mice: possible role of prefrontal cortical-hippocampal functional connectivity and metabolomic profiles
title_short Age-related differences in affective behaviors in mice: possible role of prefrontal cortical-hippocampal functional connectivity and metabolomic profiles
title_sort age related differences in affective behaviors in mice possible role of prefrontal cortical hippocampal functional connectivity and metabolomic profiles
topic aging
brain maturation
fMRI
fear conditioning
locomotor activity
functional connectivity
url https://www.frontiersin.org/articles/10.3389/fnagi.2024.1356086/full
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