Deletion of dopamine D2 receptors from parvalbumin interneurons in mouse causes schizophrenialike phenotypes

MARÍA LUCILA BECHELLI; MARIANO DI GUILMI; BELÉN ELGOYHEN; MORA OGANDO; FERNANDA DE FINO; ANTONIA MARIN-BURGIN; MARÍA EUGENIA TOMASELLA; CAMILO JUAN MININNI; SILVANO ZANUTTO; DIEGO M. GELMAN

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

NATL ACAD SCIENCES

Lugar: Washington DC, USA; Año: 2018

0027-8424

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 beenproposed 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 ofschizophrenia-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.