Dysregulation of the Synaptic Cytoskeleton in the PFC Drives Neural Circuit Pathology, Leading to Social Dysfunction
Summary: Psychiatric disorders are highly heritable pathologies of altered neural circuit functioning. How genetic mutations lead to specific neural circuit abnormalities underlying behavioral disruptions, however, remains unclear. Using circuit-selective transgenic tools and a mouse model of malada...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-07-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124720309463 |
| _version_ | 1828392409005817856 |
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| author | Il Hwan Kim Namsoo Kim Sunwhi Kim Koji Toda Christina M. Catavero Jamie L. Courtland Henry H. Yin Scott H. Soderling |
| author_facet | Il Hwan Kim Namsoo Kim Sunwhi Kim Koji Toda Christina M. Catavero Jamie L. Courtland Henry H. Yin Scott H. Soderling |
| author_sort | Il Hwan Kim |
| collection | DOAJ |
| description | Summary: Psychiatric disorders are highly heritable pathologies of altered neural circuit functioning. How genetic mutations lead to specific neural circuit abnormalities underlying behavioral disruptions, however, remains unclear. Using circuit-selective transgenic tools and a mouse model of maladaptive social behavior (ArpC3 mutant), we identify a neural circuit mechanism driving dysfunctional social behavior. We demonstrate that circuit-selective knockout (ctKO) of the ArpC3 gene within prefrontal cortical neurons that project to the basolateral amygdala elevates the excitability of the circuit neurons, leading to disruption of socially evoked neural activity and resulting in abnormal social behavior. Optogenetic activation of this circuit in wild-type mice recapitulates the social dysfunction observed in ArpC3 mutant mice. Finally, the maladaptive sociability of ctKO mice is rescued by optogenetically silencing neurons within this circuit. These results highlight a mechanism of how a gene-to-neural circuit interaction drives altered social behavior, a common phenotype of several psychiatric disorders. |
| first_indexed | 2024-12-10T07:20:19Z |
| format | Article |
| id | doaj.art-80fdaa82f368441283f372160b6264f9 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-10T07:20:19Z |
| publishDate | 2020-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-80fdaa82f368441283f372160b6264f92022-12-22T01:57:50ZengElsevierCell Reports2211-12472020-07-01324107965Dysregulation of the Synaptic Cytoskeleton in the PFC Drives Neural Circuit Pathology, Leading to Social DysfunctionIl Hwan Kim0Namsoo Kim1Sunwhi Kim2Koji Toda3Christina M. Catavero4Jamie L. Courtland5Henry H. Yin6Scott H. Soderling7Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN, USA; Department of Psychiatry and Behavioral Sciences, Duke University Medical School, Durham, NC, USADepartment of Psychology and Neuroscience, Duke University, Durham, NC, USADepartment of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN, USADepartment of Psychology and Neuroscience, Duke University, Durham, NC, USADepartment of Cell Biology, Duke University Medical School, Durham, NC, USADepartment of Cell Biology, Duke University Medical School, Durham, NC, USA; Department of Neurobiology, Duke University Medical School, Durham, NC, USADepartment of Psychology and Neuroscience, Duke University, Durham, NC, USA; Department of Neurobiology, Duke University Medical School, Durham, NC, USADepartment of Cell Biology, Duke University Medical School, Durham, NC, USA; Department of Neurobiology, Duke University Medical School, Durham, NC, USA; Corresponding authorSummary: Psychiatric disorders are highly heritable pathologies of altered neural circuit functioning. How genetic mutations lead to specific neural circuit abnormalities underlying behavioral disruptions, however, remains unclear. Using circuit-selective transgenic tools and a mouse model of maladaptive social behavior (ArpC3 mutant), we identify a neural circuit mechanism driving dysfunctional social behavior. We demonstrate that circuit-selective knockout (ctKO) of the ArpC3 gene within prefrontal cortical neurons that project to the basolateral amygdala elevates the excitability of the circuit neurons, leading to disruption of socially evoked neural activity and resulting in abnormal social behavior. Optogenetic activation of this circuit in wild-type mice recapitulates the social dysfunction observed in ArpC3 mutant mice. Finally, the maladaptive sociability of ctKO mice is rescued by optogenetically silencing neurons within this circuit. These results highlight a mechanism of how a gene-to-neural circuit interaction drives altered social behavior, a common phenotype of several psychiatric disorders.http://www.sciencedirect.com/science/article/pii/S2211124720309463social behaviorprefrontal cortexbasolateral amygdalaneural circuitcircuit pathologyschizophrenia |
| spellingShingle | Il Hwan Kim Namsoo Kim Sunwhi Kim Koji Toda Christina M. Catavero Jamie L. Courtland Henry H. Yin Scott H. Soderling Dysregulation of the Synaptic Cytoskeleton in the PFC Drives Neural Circuit Pathology, Leading to Social Dysfunction Cell Reports social behavior prefrontal cortex basolateral amygdala neural circuit circuit pathology schizophrenia |
| title | Dysregulation of the Synaptic Cytoskeleton in the PFC Drives Neural Circuit Pathology, Leading to Social Dysfunction |
| title_full | Dysregulation of the Synaptic Cytoskeleton in the PFC Drives Neural Circuit Pathology, Leading to Social Dysfunction |
| title_fullStr | Dysregulation of the Synaptic Cytoskeleton in the PFC Drives Neural Circuit Pathology, Leading to Social Dysfunction |
| title_full_unstemmed | Dysregulation of the Synaptic Cytoskeleton in the PFC Drives Neural Circuit Pathology, Leading to Social Dysfunction |
| title_short | Dysregulation of the Synaptic Cytoskeleton in the PFC Drives Neural Circuit Pathology, Leading to Social Dysfunction |
| title_sort | dysregulation of the synaptic cytoskeleton in the pfc drives neural circuit pathology leading to social dysfunction |
| topic | social behavior prefrontal cortex basolateral amygdala neural circuit circuit pathology schizophrenia |
| url | http://www.sciencedirect.com/science/article/pii/S2211124720309463 |
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