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Cited by 197Memory and Neural MechanismsGut microbiota and healthNeuroscience and Neuropharmacology Research

The microbiome regulates amygdala-dependent fear recall

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Hoban, A E, Stilling, R M, Moloney, G, Shanahan, F, Dinan, T G, Clarke, G, Cryan, J F·2018·Molecular Psychiatry
DOI 10.1038/mp.2017.100PMC PMC5984090
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Abstract

The amygdala is a key brain region that is critically involved in the processing and expression of anxiety and fear-related signals. In parallel, a growing number of preclinical and human studies have implicated the microbiome-gut-brain in regulating anxiety and stress-related responses. However, the role of the microbiome in fear-related behaviours is unclear. To this end we investigated the importance of the host microbiome on amygdala-dependent behavioural readouts using the cued fear conditioning paradigm. We also assessed changes in neuronal transcription and post-transcriptional regulation in the amygdala of naive and stimulated germ-free (GF) mice, using a genome-wide transcriptome profiling approach. Our results reveal that GF mice display reduced freezing during the cued memory retention test. Moreover, we demonstrate that under baseline conditions, GF mice display altered transcriptional profile with a marked increase in immediate-early genes (for example, Fos, Egr2, Fosb, Arc) as well as genes implicated in neural activity, synaptic transmission and nervous system development. We also found a predicted interaction between mRNA and specific microRNAs that are differentially regulated in GF mice. Interestingly, colonized GF mice (ex-GF) were behaviourally comparable to conventionally raised (CON) mice. Together, our data demonstrates a unique transcriptional response in GF animals, likely because of already elevated levels of immediate-early gene expression and the potentially underlying neuronal hyperactivity that in turn primes the amygdala for a different transcriptional response. Thus, we demonstrate for what is to our knowledge the first time that the presence of the host microbiome is crucial for the appropriate behavioural response during amygdala-dependent memory retention.

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  • These behavioral changes are accompanied by altered amygdala gene expression, specifically elevated baseline amygdala activity and reduced responsiveness to fear stimuli in GF animals.

    “These behavioral changes were accompanied by altered amygdala gene expression, specifically indicating elevated baseline amygdala activity and reduced responsiveness to the fear stimuli in the GF animals.”

    From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Hoban et al., 2018

  • Six hours after fear conditioning, GF animals exhibit low levels of conditioned fear responding relative to conventionally-colonized animals, but this deficit is rescued in ex-GF mice re-colonized at weaning.

    “Six hours later, GF animals exhibited low levels of conditioned fear responding relative to conventionally-colonized animals, but this deficit was rescued in the ex-GF mice that were re-colonized at weaning.”

    From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Hoban et al., 2018

  • In GF mice, short-term fear recall is impaired in the absence of the microbiota.

    “With GF mice, short-term fear recall was shown to be impaired in the absence of the microbiota (Hoban et al., 2018).”

    From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Hoban et al., 2018

  • Germ-free animals show a marked increase in immediate-early gene (Fos, Egr2, Fosb, Arc) expression in the amygdala.

    “combined with a marked increase in immediate-early gene (Fos, Egr2, Fosb, Arc) expression in the amygdala (Hoban et al., 2018)”

    From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Hoban et al., 2018

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Cited by

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Authors
Hoban, A. E., Stilling, R. M., Moloney, G., Shanahan, F., Dinan, T. G., Clarke, G., & Cryan, J. F.
Affiliations
University College Cork (IE)
Corresponding author
  • Clarke, G
  • Cryan, J F
ORCID
Venue
Molecular Psychiatry
Publisher
Springer Science and Business Media LLC
Published
2017-05-16
Volume
23
Issue
5
Pages
1134-1144
ISSN
  • 1359-4184 (ISSN-L)
  • 1476-5578
DOI
10.1038/mp.2017.100
PMC
PMC5984090
OpenAlex
W2614977323
Cited by
197
References
13
Citations by year
2026: 13 · 2025: 16 · 2024: 20 · 2023: 14 · 2022: 17 · 2021: 31 · 2020: 36 · 2019: 22 · 2018: 23 · 2017: 5
FWCI
13.49
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Psychiatry (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Arrow@dit (Dublin Institute of Technology) (submittedVersion, cc-by-nc-nd)
Funders
  • Brain and Behavior Research Foundation (20771)
  • National Alliance for Research on Schizophrenia and Depression (20771)
  • Enterprise Ireland
  • Science Foundation Ireland (20771, 12/RC/2273, 12/RC/)
  • Irish Research Council
  • APC Microbiome Institute
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
gut microbiota, microbiome-gut-brain axis, amygdala, fear memory, cued fear conditioning, germ-free mice, immediate early genes, gene expression profiling, microRNA, synaptic transmission, neuronal hyperactivity, anxiety
MeSH terms
Gastrointestinal Microbiome, Amygdala, Animals, Anxiety, Brain, Cues, Fear, Gene Expression Regulation, Male, Memory, Mice, Inbred C57BL, Neurons, Mental Recall, RNA, Messenger, Sequence Analysis, RNA, Mice, Transcriptome, Gene Ontology

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