摘要:SummaryThe substantia nigra (SN) and ventral tegmental area (VTA) are vital for the control of movement, goal-directed behavior, and encoding reward. Here we show that the firing of specific neuronal subtypes in these nuclei can be modulated by physiological changes in the partial pressure of carbon dioxide (PCO2). The resting conductance of substantia nigra dopaminergic neurons in young animals (postnatal days 7–10) and GABAergic neurons in the VTA is modulated by changes in the level of CO2. We provide several lines of evidence that this CO2-sensitive conductance results from connexin 26 (Cx26) hemichannel expression. Since the levels of PCO2in the blood will vary depending on physiological activity and pathology, this suggests that changes in PCO2could potentially modulate motor activity, reward behavior, and wakefulness.Graphical AbstractDisplay OmittedHighlights•The substantia nigra (SN) and VTA are key to movement and goal-directed behavior•Activity in specific SN and VTA neurons is modulated by physiological changes in CO2•The neuronal CO2sensitivity results from connexin 26 (Cx26) hemichannel expression•Minute-to-minute changes in CO2could modify motor activity and reward behaviorMolecular Neuroscience; Cellular Neuroscience