Cognitive representations of intracranial self-stimulation of midbrain dopamine neurons depend on stimulation frequency

• Published in: Nature neuroscience 2024-07, Vol.27 (7), p.1253-1259
• Main Authors: Millard, Samuel J., Hoang, Ivy B., Sherwood, Savannah, Taira, Masakazu, Reyes, Vanessa, Greer, Zara, O’Connor, Shayna L., Wassum, Kate M., James, Morgan H., Barker, David J., Sharpe, Melissa J.
• Format: Article
• Language: English
• Subjects: 13; 14; 14/1; 14/19; 38; 42; 59; 631/378/1662; 631/378/1788; 631/378/3920; 82; 9/10; 96; Action Potentials - physiology; Animal Genetics and Genomics; Animals; Behavioral Sciences; Biological Techniques; Biomedical and Life Sciences; Biomedicine; Brief Communication; Cognition - physiology; Dopamine; Dopamine - metabolism; Dopaminergic Neurons - physiology; Electric Stimulation - methods; Food; Frequency dependence; Intracranial self-stimulation; Macaca mulatta; Male; Mesencephalon; Mesencephalon - physiology; Neurobiology; Neurons; Neurosciences; Reinforcement; Representations; Reward; Schedules; Self Stimulation - physiology; Self-stimulation; Sensory neurons; Stimulation; Ventral Tegmental Area - physiology; Ventral tegmentum
• ISSN: 1097-6256; 1546-1726; 1546-1726
• DOI: 10.1038/s41593-024-01643-1

Dopamine neurons in the ventral tegmental area support intracranial self-stimulation (ICSS), yet the cognitive representations underlying this phenomenon remain unclear. Here, 20-Hz stimulation of dopamine neurons, which approximates a physiologically relevant prediction error, was not sufficient to support ICSS beyond a continuously reinforced schedule and did not endow cues with a general or specific value. However, 50-Hz stimulation of dopamine neurons was sufficient to drive robust ICSS and was represented as a specific reward to motivate behavior. The frequency dependence of this effect is due to the rate (not the number) of action potentials produced by dopamine neurons, which differently modulates dopamine release downstream. Physiologically relevant stimulation of dopamine neurons does not function as a reward and does not endow cues with a reward representation. However, high-frequency stimulation is represented as a sensory-specific goal that motivates behavior.