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Deletion of dopamine D2 receptors from parvalbumin interneurons in mouse causes schizophrenia-like phenotypes.


ABSTRACT: Excessive dopamine neurotransmission underlies psychotic episodes as observed in patients with some types of bipolar disorder and schizophrenia. The dopaminergic hypothesis was postulated after the finding that antipsychotics were effective to halt increased dopamine tone. However, there is little evidence for dysfunction within the dopaminergic system itself. Alternatively, it has been proposed that excessive afferent activity onto ventral tegmental area dopaminergic neurons, particularly from the ventral hippocampus, increase dopamine neurotransmission, leading to psychosis. Here, we show that selective dopamine D2 receptor deletion from parvalbumin interneurons in mouse causes an impaired inhibitory activity in the ventral hippocampus and a dysregulated dopaminergic system. Conditional mutant animals show adult onset of schizophrenia-like behaviors and molecular, cellular, and physiological endophenotypes as previously described from postmortem brain studies of patients with schizophrenia. Our findings show that dopamine D2 receptor expression on parvalbumin interneurons is required to modulate and limit pyramidal neuron activity, which may prevent the dysregulation of the dopaminergic system.

SUBMITTER: Tomasella E 

PROVIDER: S-EPMC5879696 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Deletion of dopamine D<sub>2</sub> receptors from parvalbumin interneurons in mouse causes schizophrenia-like phenotypes.

Tomasella Eugenia E   Bechelli Lucila L   Ogando Mora Belén MB   Mininni Camilo C   Di Guilmi Mariano N MN   De Fino Fernanda F   Zanutto Silvano S   Elgoyhen Ana Belén AB   Marin-Burgin Antonia A   Gelman Diego M DM  

Proceedings of the National Academy of Sciences of the United States of America 20180312 13


Excessive dopamine neurotransmission underlies psychotic episodes as observed in patients with some types of bipolar disorder and schizophrenia. The dopaminergic hypothesis was postulated after the finding that antipsychotics were effective to halt increased dopamine tone. However, there is little evidence for dysfunction within the dopaminergic system itself. Alternatively, it has been proposed that excessive afferent activity onto ventral tegmental area dopaminergic neurons, particularly from  ...[more]

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