Chemogenetic Interrogation of a Brain-wide Fear Memory Network in Mice.
Identifieur interne : 000112 ( Main/Exploration ); précédent : 000111; suivant : 000113Chemogenetic Interrogation of a Brain-wide Fear Memory Network in Mice.
Auteurs : Gisella Vetere [Canada] ; Justin W. Kenney [Canada] ; Lina M. Tran [Canada] ; Frances Xia [Canada] ; Patrick E. Steadman [Canada] ; John Parkinson [Canada] ; Sheena A. Josselyn [Canada] ; Paul W. Frankland [Canada]Source :
- Neuron [ 1097-4199 ] ; 2017.
Abstract
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.
DOI: 10.1016/j.neuron.2017.03.037
PubMed: 28426969
Affiliations:
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Steadman</name><affiliation wicri:level="4"><nlm:affiliation>Program in Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Program in Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Parkinson, John" sort="Parkinson, John" uniqKey="Parkinson J" first="John" last="Parkinson">John Parkinson</name><affiliation wicri:level="4"><nlm:affiliation>Program in Molecular Structure and Function, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Departments of Biochemistry, Computer Science, and Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Program in Molecular Structure and Function, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Departments of Biochemistry, Computer Science, and Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Josselyn, Sheena A" sort="Josselyn, Sheena A" uniqKey="Josselyn S" first="Sheena A" last="Josselyn">Sheena A. Josselyn</name><affiliation wicri:level="4"><nlm:affiliation>Program in Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada; Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Psychology, University of Toronto, Toronto, ON M5S 3GM, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Program in Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada; Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Psychology, University of Toronto, Toronto, ON M5S 3GM</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Frankland, Paul W" sort="Frankland, Paul W" uniqKey="Frankland P" first="Paul W" last="Frankland">Paul W. Frankland</name><affiliation wicri:level="4"><nlm:affiliation>Program in Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada; Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Psychology, University of Toronto, Toronto, ON M5S 3GM, Canada. Electronic address: paul.frankland@sickkids.ca.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Program in Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada; Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Psychology, University of Toronto, Toronto, ON M5S 3GM</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author></analytic><series><title level="j">Neuron</title><idno type="eISSN">1097-4199</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><affiliations><list><country><li>Canada</li></country><region><li>Ontario</li></region><settlement><li>Toronto</li></settlement><orgName><li>Université de Toronto</li></orgName></list><tree><country name="Canada"><noRegion><name sortKey="Vetere, Gisella" sort="Vetere, Gisella" uniqKey="Vetere G" first="Gisella" last="Vetere">Gisella Vetere</name></noRegion><name sortKey="Frankland, Paul W" sort="Frankland, Paul W" uniqKey="Frankland P" first="Paul W" last="Frankland">Paul W. Frankland</name><name sortKey="Josselyn, Sheena A" sort="Josselyn, Sheena A" uniqKey="Josselyn S" first="Sheena A" last="Josselyn">Sheena A. Josselyn</name><name sortKey="Kenney, Justin W" sort="Kenney, Justin W" uniqKey="Kenney J" first="Justin W" last="Kenney">Justin W. Kenney</name><name sortKey="Parkinson, John" sort="Parkinson, John" uniqKey="Parkinson J" first="John" last="Parkinson">John Parkinson</name><name sortKey="Steadman, Patrick E" sort="Steadman, Patrick E" uniqKey="Steadman P" first="Patrick E" last="Steadman">Patrick E. Steadman</name><name sortKey="Tran, Lina M" sort="Tran, Lina M" uniqKey="Tran L" first="Lina M" last="Tran">Lina M. Tran</name><name sortKey="Xia, Frances" sort="Xia, Frances" uniqKey="Xia F" first="Frances" last="Xia">Frances Xia</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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