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Midbrain dopamine neurons, which can be regulated by neuropeptides and hormones, play a fundamental role in controlling cognitive processes, reward mechanisms, and motor functions. The hormonal actions of insulin-like growth factor 1 (IGF-1) produced by the liver have been well described, but the role of neuronally derived IGF-1 remains largely unexplored. We discovered that dopamine neurons secrete IGF-1 from the cell bodies following depolarization, and that IGF-1 controls release of dopamine in the ventral midbrain. In addition, conditional deletion of dopamine neuron-derived IGF-1 in adult mice leads to decrease of dopamine content in the striatum and deficits in dopamine neuron firing and causes reduced spontaneous locomotion and impairments in explorative and learning behaviors. These data identify that dopamine neuron-derived IGF-1 acts as a regulator of dopamine neurons and regulates dopamine-mediated behaviors.

Original publication

DOI

10.1073/pnas.1806820116

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

26/02/2019

Volume

116

Pages

3817 - 3826

Keywords

IGF-1, behavior, dopamine, firing, somatodendritic, Animals, Cognition, Corpus Striatum, Dopaminergic Neurons, Exploratory Behavior, Hormones, Insulin-Like Growth Factor I, Learning, Locomotion, Mesencephalon, Mice, Neuropeptides