Selective deletion of Dopamine D2 Receptor in fast spiking interneurons: Implication in psychiatric disorders

TOMASELLA, M.E.; OGANDO M.; ZANUTTO, S.; MININI C.; ELGOYHEN, B.; GELMAN, D.M; BECHELLI, M.L.; DI GUILMI, M.; MARIN-BURGIN, A.

Buenos Aires

Congreso; Sociedad Argentina de Neurociencias-FALAN 2016; 2016

SAN-FALAN

The dopaminesystem has been implicated in different brain functions including affect,cognition and memory. It´s dysfunction has been implicated in psychiatricdiseases like bipolar disorder, depression and schizophrenia. GABAergic interneuronsare responsible of maintaining adequate excitatory-inhibitory balance. Amongthe population of interneurons, Parvalbumin (PV) positive fast spikinginterneurons seems to play a central role in the control of this balance. Interestingly,PV interneuron dysfunction was also related to psychiatric disorders, by anoverdrive of the dopaminergic system. Animal models of psychiatric diseasespoints to a hyper-responsive dopamine system as a result of ventral hippocampaldisinhibition. To test the relevanceof dopaminergic tone over PV interneurons, we selectively deleted dopamine D2 receptor in thispopulation. Our results showed a hyperactive hippocampus. As a consequence, weobserved hyperactive dopaminergic system. Neuronal network dysfunctions wereaccompanied by reduced expression mRNA levels of relevant related genes. Behavioral analyses resulted in a pronounced increasein locomotor activity, altered anxiety, cognitive dysfunction and lack of motivation. In summary, our results showedneuronal circuit perturbations with functional consequences in behavior,suggesting that dopamine D2 receptor in PV interneurons exerts an essentialrole during brain development to accomplish adequately balanced neuronalensembles.