Chemogenetic Interrogation of a Brain-wide Fear Memory Network in Mice
Open accessAbstract
Behavior depends on coordinated activity across multiple brain regions. Within such networks, highly connected hub regions are assumed to disproportionately influence behavioral output, although this hypothesis has not been systematically evaluated. Previously, by mapping brain-wide expression of the activity-regulated gene c-fos, we identified a network of brain regions co-activated by fear memory. To test the hypothesis that hub regions are more important for network function, here, we simulated node deletion in silico in this behaviorally defined functional network. Removal of high degree nodes produced the greatest network disruption (e.g., reduction in global efficiency). To test these predictions in vivo, we examined the impact of post-training chemogenetic silencing of different network nodes on fear memory consolidation. In a series of independent experiments encompassing 25% of network nodes (i.e., 21/84 brain regions), we found that node degree accurately predicted observed deficits in memory consolidation, with silencing of highly connected hubs producing the largest impairments.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Sample sizes were initially determined based on prior work using social interaction and intrinsic physiology, and no formal statistical methods were used to pre-determine sample sizes.
“Sample sizes were initially determined based on prior work using social interaction54,65 and intrinsic physiology62, no formal statistical methods were used to pre-determine sample sizes.”
From Insular cortex mediates approach and avoidance responses to social affective stimuli (2018) · cites this paper as [65]
Cites
Cytoscape: A software Environment for integrated models of biomolecular interaction networks
Shannon, P., Markiel, A., Ozier, O., Baliga, N. S., Wang, J. T., Ramage, D., Amin, N., Schwikowski, B., & Ideker, T. (2003) · Genome Research · doi:10.1101/gr.1239303 · Cited by 51,888 · see citing works
Error and attack tolerance of complex networks
Albert, R., Jeong, H., & Barabási, A.-L. (2000) · Nature · doi:10.1038/35019019 · Cited by 7,534 · see citing works
The structure of the nervous system of the nematode <i>Caenorhabditis elegans</i>
White, J. G., Southgate, E., Thomson, J. N., & Brenner, S. (1986) · Philosophical Transactions of the Royal Society of London. B, Biological Sciences · doi:10.1098/rstb.1986.0056 · Cited by 5,589 · cited 2× · see citing works
“…used to describe large-scale structural (i.e., anatomical) and functional (i.e., coactivation) connections in the brain (Bargmann and Marder, 2013; Bullmore and Sporns, 2012; Chiang et al., 2011; Jarrell et al., 2012; Markov et al., 2014; Oh et al., 2014; Varshney et al., 2011; White et al., 1986).”
BackgroundSystemic risk in banking ecosystems
Haldane, A. G., & May, R. M. (2011) · Nature · doi:10.1038/nature09659 · Cited by 1,480 · see citing works
Sporns, O., & Betzel, R. F. (2016) · Annual Review of Psychology · doi:10.1146/annurev-psych-122414-033634 · Cited by 1,334 · see citing works
Network attributes for segregation and integration in the human brain
Sporns, O. (2013) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2012.11.015 · Cited by 1,067 · see citing works
Mapping of Brain Activity by Automated Volume Analysis of Immediate Early Genes
Renier, N., Adams, E. L., Kirst, C., Wu, Z., Azevedo, R., Kohl, J., Autry, A. E., Kadiri, L., Umadevi Venkataraju, K., Zhou, Y., et al. (2016) · Cell · doi:10.1016/j.cell.2016.05.007 · Cited by 918 · see citing works
Beck, C., & Fibiger, H. (1995) · The Journal of Neuroscience · doi:10.1523/jneurosci.15-01-00709.1995 · Cited by 547 · see citing works
Molecular interrogation of hypothalamic organization reveals distinct dopamine neuronal subtypes
Romanov, R. A., Zeisel, A., Bakker, J., Girach, F., Hellysaz, A., Tomer, R., Alpár, A., Mulder, J., Clotman, F., Keimpema, E., et al. (2017) · Nature Neuroscience · doi:10.1038/nn.4462 · Cited by 502 · see citing works
Linking context with reward: a functional circuit from hippocampal CA3 to ventral tegmental area
Luo, A. H., Tahsili-Fahadan, P., Wise, R. A., Lupica, C. R., & Aston-Jones, G. (2011) · Science · doi:10.1126/science.1204622 · Cited by 425 · see citing works
Identification of a Functional Connectome for Long-Term Fear Memory in Mice
Wheeler, A. L., Teixeira, C. M., Wang, A. H., Xiong, X., Kovacevic, N., Lerch, J. P., McIntosh, A. R., Parkinson, J., & Frankland, P. W. (2013) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002853 · Cited by 315 · see citing works
Self-citationAge-related differences in the functional connectivity of the hippocampus during memory encoding
Grady, C. L., McIntosh, A. R., & Craik, F. I. M. (2003) · Hippocampus · doi:10.1002/hipo.10114 · Cited by 277 · see citing works
Grayson, D. S., Bliss-Moreau, E., Machado, C. J., Bennett, J., Shen, K., Grant, K. A., Fair, D. A., & Amaral, D. G. (2016) · Neuron · doi:10.1016/j.neuron.2016.06.005 · Cited by 172 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Memory engrams: Recalling the past and imagining the future
Josselyn, S. A., & Tonegawa, S. (2020) · Science · doi:10.1126/science.aaw4325 · Cited by 1,087 · see citing works
Self-citationDisruption of oligodendrogenesis impairs memory consolidation in adult mice
Steadman, P. E., Xia, F., Ahmed, M., Mocle, A. J., Penning, A. R. A., Geraghty, A. C., Steenland, H. W., Monje, M., Josselyn, S. A., & Frankland, P. W. (2020) · Neuron · doi:10.1016/j.neuron.2019.10.013 · Cited by 426 · see citing works
Self-citationThe hippocampus and related neocortical structures in memory transformation
Sekeres, M. J., Winocur, G., & Moscovitch, M. (2018) · Neuroscience Letters · doi:10.1016/j.neulet.2018.05.006 · Cited by 370 · see citing works
Insular cortex mediates approach and avoidance responses to social affective stimuli
Rogers-Carter, M. M., Varela, J. A., Gribbons, K. B., Pierce, A. F., McGoey, M. T., Ritchey, M., & Christianson, J. P. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0071-y · Cited by 277 · see citing works
The neurobiological foundation of memory retrieval
Frankland, P. W., Josselyn, S. A., & Köhler, S. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0493-1 · Cited by 228 · see citing works
Self-citationRatigan, H. C., Krishnan, S., Smith, S., & Sheffield, M. E. J. (2023) · Nature Communications · doi:10.1038/s41467-023-42429-6 · Cited by 60 · see citing works
- Authors
- Vetere, G., Kenney, J. W., Tran, L. M., Xia, F., Steadman, P. E., Parkinson, J., Josselyn, S. A., & Frankland, P. W.
- Affiliations
- Hospital for Sick Children (CA)
- University of Toronto (CA)
- Corresponding author
- Frankland, Paul W.
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2017-04
- Volume
- 94
- Issue
- 2
- Pages
- 363-374.e4
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2605615531
- Cited by
- 293
- References
- 13
- Citations by year
- 2026: 19 · 2025: 40 · 2024: 35 · 2023: 43 · 2022: 27 · 2021: 34 · 2020: 39 · 2019: 22 · 2018: 31 · 2017: 3
- FWCI
- 14.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, public-domain)
- Funders
- Canadian Institutes of Health Research (CIHR) (FDN143227, MOP74650)
- Natural Sciences and Engineering Research Council (NSERC) (RGPIN-2014-06664)
- Human Frontiers Science Program (LT000759/2014)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory Processes and Influences
- Keywords
- fear memory, memory consolidation, hub regions, node degree, network efficiency, chemogenetic silencing, Fos expression, network disruption, node removal
- MeSH terms
- Animals, Brain, Brain Mapping, Conditioning, Psychological, Fear, Image Processing, Computer-Assisted, Male, Memory, Nerve Net, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
