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Nella

PhD Doctor of Philosophy candidate

Subjects
Other, Neuroscience, Biology
Expertise
Neuroscience, Cellular Biology and Viruses
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Project ideas

Interneuron-localized Dopamine D1 receptors as a novel therapeutic target for Major Depression

Major depressive disorder (MDD) is a common mental health disorder estimated to affect more than 264 million people worldwide. Currently, one of the limitations of available treatments affect one third of people with major depression who develop treatment-resistance. Previous studies found important roles for the neurotransmitter dopamine in regulating moods. Additional studies found that some interneurons receive synaptic input from dopaminergic axons, and express DA D1 and D2 receptors whereas other cortical interneurons rarely express DA signaling components. Importantly, the lineage of these fast-spiking cortical interneurons, derived from the medial ganglionic eminence (MGE) in the developing forebrain, is controlled in part by the transcription factor Nkx2.1. This information opens up a new gate for possible mechanism by which an antidepressant effect can be achieved. Using the Cre-loxP system, we selectively deleted Drd1 from medial ganglionic eminence-derived GABAergic neurons (using Nkx2.1-Cre; GABA-Drd1-cKO) in mice. We noticed strong antidepressant-like effects from loss of these D1 receptors as well as a reduction of stress hormone, corticosteroid, at baseline. We will further assess cellular adaptations and peripheral stress responses recruited due to the loss of Drd1 in our model system (MGE-Drd1-cKO mice) which may render them resistant to stress. Ideally, pursuing a deeper physiological and neural understanding of the neuroadaptations that accompany Drd1 loss from GABAergic interneurons derived from the embryonic MGE, will allow us to develop potentially innovative strategies to use in the development of new and unique therapeutics for the treatment of MDD.

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