Three aspects need to be highlighted: first, it is the overactivity of this pathway rather than the alteration of the density of its constituents that ensures the overactivation of A2AR. In other words, the increased contribution of A2AR to the increased corticostriatal LTP magnitude during presymptomatic PD is not due to an increased density of CD73 or of A2AR but rather to an increased activity of CD73 and of A2AR driven by an increased synaptic release of ATP, i.e., it is a change of software rather than of hardware. The gene discussed is ADORA2A; the disease is Parkinson disease.