The role of glutamatergic synaptic transmission onto midbrain dopamine neurons in reward-related behaviors

Monday, September 22, 2014 — Poster Session I
12:00 p.m. – 2:00 p.m.	FAES Academic Center	NINDS	NEURO-10

* FARE Award Winner

Authors

• MA Hutchison
• MR Lee
• W Lu

Abstract

Dopamine (DA) release is critically involved in motivated and reward-related behavior. DA neurons show a variety of firing patterns which are regulated by the activation of glutamate receptors. A better understanding of these glutamate-DA interactions will help to identify the biological mechanisms underlying reward-related behaviors. For this, we developed a quadruple conditional knockout mouse line in which genes encoding three AMPAR and one NMDAR subunit are all conditional alleles, and crossed a DAT-Cre knock-in mouse line to generate GRIA1-3fl/flGRIN1fl/fl/DAT-Cre mice. Immunohistochemistry and electrophysiology were used to confirm the loss of the receptor subunits. In a battery of behavioral tests, we found that neither gross movement nor motor coordination were altered in the mutant mice. In addition, no differences were seen in a sucrose preference test or with food-based learning tests. Therefore, we have shown that DA activation via glutamate receptors is not crucial for the response to natural reinforcers. Further studies are ongoing to determine the role of glutamate receptors in the response to cocaine and other behaviors related to dopamine signaling. Together, the results of these studies will clarify the biological underpinnings of reward-related behaviors such as drug addiction, and will hopefully provide targets for therapeutic interventions.

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