Moderate Changes in CO(2) Modulate the Firing of Neurons in the VTA and Substantia Nigra

The 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 (PCO(2)). 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 CO(2). We provide several lines of evidence that this CO(2)-sensitive conductance results from connexin 26 (Cx26) hemichannel expression. Since the levels of PCO(2) in the blood will vary depending on physiological activity and pathology, this suggests that changes in PCO(2) could potentially modulate motor activity, reward behavior, and wakefulness.