Dopamine neuron-derived IGF-1 controls dopamine neuron firing, skill learning, and exploration Alessandro Pristerà Craig Blomeley Emanuel Lopes Sarah Threlfell Elisa Merlini Denis Burdakov Stephanie Cragg François Guillemot Siew-Lan Ang 10779/crick.11409375.v1 https://crick.figshare.com/articles/journal_contribution/Dopamine_neuron-derived_IGF-1_controls_dopamine_neuron_firing_skill_learning_and_exploration/11409375 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. 2019-12-19 18:08:48 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 Guillemot FC001089 Burdakov FC001055