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Excess dopamine D2R activation accounts for PV+ basket cell and learning alterations in mouse model of schizophrenia

Pereira, Fernando Carvalho Rodrigues. Excess dopamine D2R activation accounts for PV+ basket cell and learning alterations in mouse model of schizophrenia. 2016, Doctoral Thesis, University of Basel, Faculty of Science.

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Official URL: http://edoc.unibas.ch/diss/DissB_12156

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Abstract

Schizophrenia is consistently associated with alterations in parvalbumin-positive basket cell functions, and with reduced gamma power of network activity, but causal relationships between PV dysfunctions and clinical manifestations of schizophrenia have remained unclear. Here I investigated LgDel+/- mice, a genetic model closely reproducing chromosomal deletions in 22q11 patients. I found that early-born PV interneurons are specifically affected in the LgDel+/- mice, suggesting a specific deficit in synaptic excitation of PV neurons. The PV alterations were associated with specific deficits in long-term memory consolidation and in top-down executive control. Delivery of the D2-receptor antagonist haloperidol to mutant mice rescued PV network alterations and long-term memory. My findings are consistent with the notion that PV network deregulation has an important role in cognitive deficits of schizophrenia model mice.
Advisors:Caroni, Pico and Roska, Botond
Faculties and Departments:09 Associated Institutions > Friedrich Miescher Institut FMI > Neurobiology > Plasticity of neuronal connections (Caroni)
UniBasel Contributors:Roska, Botond
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:12156
Thesis status:Complete
Number of Pages:1 Online-Ressource (101 Blätter)
Language:English
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Last Modified:22 Jan 2018 15:52
Deposited On:21 Jun 2017 14:14

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