Schizophrenia-Related Microdeletion Impairs Emotional Memory through MicroRNA-Dependent Disruption of Thalamic Inputs to the Amygdala
Individuals with 22q11.2 deletion syndrome (22q11DS) are at high risk of developing psychiatric diseases such as schizophrenia. Individuals with 22q11DS and schizophrenia are impaired in emotional memory, anticipating, recalling, and assigning a correct context to emotions. The neuronal circuits res...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-05-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124717306083 |
| _version_ | 1828232167302365184 |
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| author | Tae-Yeon Eom Ildar T. Bayazitov Kara Anderson Jing Yu Stanislav S. Zakharenko |
| author_facet | Tae-Yeon Eom Ildar T. Bayazitov Kara Anderson Jing Yu Stanislav S. Zakharenko |
| author_sort | Tae-Yeon Eom |
| collection | DOAJ |
| description | Individuals with 22q11.2 deletion syndrome (22q11DS) are at high risk of developing psychiatric diseases such as schizophrenia. Individuals with 22q11DS and schizophrenia are impaired in emotional memory, anticipating, recalling, and assigning a correct context to emotions. The neuronal circuits responsible for these emotional memory deficits are unknown. Here, we show that 22q11DS mouse models have disrupted synaptic transmission at thalamic inputs to the lateral amygdala (thalamo-LA projections). This synaptic deficit is caused by haploinsufficiency of the 22q11DS gene Dgcr8, which is involved in microRNA processing, and is mediated by the increased dopamine receptor Drd2 levels in the thalamus and by reduced probability of glutamate release from thalamic inputs. This deficit in thalamo-LA synaptic transmission is sufficient to cause fear memory deficits. Our results suggest that dysregulation of the Dgcr8–Drd2 mechanism at thalamic inputs to the amygdala underlies emotional memory deficits in 22q11DS. |
| first_indexed | 2024-04-12T19:16:55Z |
| format | Article |
| id | doaj.art-4936ffd7d63544c7b21a866e3fbeb0ad |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-12T19:16:55Z |
| publishDate | 2017-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-4936ffd7d63544c7b21a866e3fbeb0ad2022-12-22T03:19:42ZengElsevierCell Reports2211-12472017-05-011981532154410.1016/j.celrep.2017.05.002Schizophrenia-Related Microdeletion Impairs Emotional Memory through MicroRNA-Dependent Disruption of Thalamic Inputs to the AmygdalaTae-Yeon Eom0Ildar T. Bayazitov1Kara Anderson2Jing Yu3Stanislav S. Zakharenko4Department of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USADepartment of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USADepartment of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USADepartment of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USADepartment of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USAIndividuals with 22q11.2 deletion syndrome (22q11DS) are at high risk of developing psychiatric diseases such as schizophrenia. Individuals with 22q11DS and schizophrenia are impaired in emotional memory, anticipating, recalling, and assigning a correct context to emotions. The neuronal circuits responsible for these emotional memory deficits are unknown. Here, we show that 22q11DS mouse models have disrupted synaptic transmission at thalamic inputs to the lateral amygdala (thalamo-LA projections). This synaptic deficit is caused by haploinsufficiency of the 22q11DS gene Dgcr8, which is involved in microRNA processing, and is mediated by the increased dopamine receptor Drd2 levels in the thalamus and by reduced probability of glutamate release from thalamic inputs. This deficit in thalamo-LA synaptic transmission is sufficient to cause fear memory deficits. Our results suggest that dysregulation of the Dgcr8–Drd2 mechanism at thalamic inputs to the amygdala underlies emotional memory deficits in 22q11DS.http://www.sciencedirect.com/science/article/pii/S221112471730608322q11.2 deletionschizophreniathalamusfear conditioningactive avoidancedopamine receptorsmicroRNA processingDgcr8, emotional memory |
| spellingShingle | Tae-Yeon Eom Ildar T. Bayazitov Kara Anderson Jing Yu Stanislav S. Zakharenko Schizophrenia-Related Microdeletion Impairs Emotional Memory through MicroRNA-Dependent Disruption of Thalamic Inputs to the Amygdala Cell Reports 22q11.2 deletion schizophrenia thalamus fear conditioning active avoidance dopamine receptors microRNA processing Dgcr8, emotional memory |
| title | Schizophrenia-Related Microdeletion Impairs Emotional Memory through MicroRNA-Dependent Disruption of Thalamic Inputs to the Amygdala |
| title_full | Schizophrenia-Related Microdeletion Impairs Emotional Memory through MicroRNA-Dependent Disruption of Thalamic Inputs to the Amygdala |
| title_fullStr | Schizophrenia-Related Microdeletion Impairs Emotional Memory through MicroRNA-Dependent Disruption of Thalamic Inputs to the Amygdala |
| title_full_unstemmed | Schizophrenia-Related Microdeletion Impairs Emotional Memory through MicroRNA-Dependent Disruption of Thalamic Inputs to the Amygdala |
| title_short | Schizophrenia-Related Microdeletion Impairs Emotional Memory through MicroRNA-Dependent Disruption of Thalamic Inputs to the Amygdala |
| title_sort | schizophrenia related microdeletion impairs emotional memory through microrna dependent disruption of thalamic inputs to the amygdala |
| topic | 22q11.2 deletion schizophrenia thalamus fear conditioning active avoidance dopamine receptors microRNA processing Dgcr8, emotional memory |
| url | http://www.sciencedirect.com/science/article/pii/S2211124717306083 |
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