Dopamine neuron-derived IGF-1 controls dopamine neuron firing, skill learning, and exploration

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 116; no. 9; pp. 3817 - 3826
• Main Authors: Pristerà, Alessandro, Blomeley, Craig, Lopes, Emanuel, Threlfell, Sarah, Merlini, Elisa, Burdakov, Denis, Cragg, Stephanie, Guillemot, François, Ang, Siew-Lan
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 26.02.2019
• Series: PNAS Plus
• Subjects: Animals; Biological Sciences; Clonal deletion; Cognition - physiology; Cognitive ability; Corpus Striatum - metabolism; Corpus Striatum - physiology; Depolarization; Dopamine; Dopaminergic Neurons - metabolism; Dopaminergic Neurons - pathology; Dopaminergic Neurons - physiology; Exploration; Exploratory Behavior - physiology; Growth factors; Hormones; Hormones - metabolism; Insulin; Insulin-like growth factor I; Insulin-Like Growth Factor I - biosynthesis; Insulin-Like Growth Factor I - genetics; Insulin-like growth factors; Learning - physiology; Learning behavior; Liver; Locomotion; Locomotion - genetics; Locomotion - physiology; Mesencephalon; Mesencephalon - metabolism; Mesencephalon - physiology; Mice; Neostriatum; Neurons; Neuropeptides; Neuropeptides - genetics; PNAS Plus; Reinforcement; firing; IGF-1; behavior; somatodendritic; dopamine
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.1806820116

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.