Locus coeruleus activation during environmental novelty gates cocaine-induced long-term hyperactivity of dopamine neurons

• Published in: iScience 2022-04, Vol.25 (4), p.104154, Article 104154
• Main Authors: Fois, Giulia R., Bosque-Cordero, Karl Y., Vazquez-Torres, Rafael, Miliano, Cristina, Nogues, Xavier, Jimenez-Rivera, Carlos A., Caille, Stéphanie, Georges, François
• Format: Article
• Language: English
• Subjects: Behavioral neuroscience; Biological sciences; Cognitive science; Life Sciences; Neuroscience
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2022.104154

A key feature of the brain is the ability to handle novelty. Anything that is new will stimulate curiosity and trigger exploration. Novelty preference has been proposed to predict increased sensitivity to cocaine. Different brain circuits are activated by novelty, but three specific brain regions are critical for exploring a novel environment: the noradrenergic neurons originating from the locus coeruleus (LC), the dopaminergic neurons from the ventral tegmental area (VTA), and the hippocampus. However, how exploring a novel environment can interfere with the reward system and control cocaine impact on VTA dopamine neuron plasticity is unclear. Here, we first investigated the effects of exposure to a novel environment on the tonic electrophysiological properties of VTA dopamine neurons. Then, we explored how exposure to a novel environment controls cocaine-evoked plasticity in dopamine neurons. Our findings indicate that LC controls VTA dopamine neurons under physiological conditions but also after cocaine. [Display omitted] •Exposure to a novel environment increases the tonic activity of dopamine neurons•Non-spatial contextual novelty had no excitatory effect on dopamine neurons•Locus coeruleus (LC) controls the impact of novelty on dopamine neurons•Novelty gates cocaine’s effect on dopamine neurons through LC activation Biological sciences; Neuroscience; Behavioral neuroscience