Paradoxical sleep has been named because it is a state paradoxically close to wakefulness (W) at the cortical level. In this context, our research group has shown using cFos mapping that only a few limbic cortical structures contain activated neurons during PS in contrast with W during which most of the cortical structures are activated. In the present study, we directly determine whether the same or different neurons are activated during W and PS using a new genetic approach. We mapped the neurons activated during W and PS in the transgenic TRAP2-red mouse model. Four male mice implanted with EEG/EMG were kept awake during 4h and received IP injection of 4-hydroxytamoxifen after the first 2h of W. One week later, they were submitted to a 48h automatic PS deprivation, followed by 2h of PS rebound before sacrifice. Sections were stained using immunofluorescence of cFos, MCH and Orx and scanned to map the distribution of tdtomato, cFos, MCH, Orx and double- and triple-labelled neurons. In the hypothalamus, MCH neurons were activated only during PS rebound and not during W (*, p>0.05). In addition, some structures were activated specifically during W like the paraventricular hypothalamic nucleus (PVN) and supraoptic nucleus (SON). In the cortex, most neurons activated during PS were not activated during W. In summary, our results clearly show that the most of the neurons activated during PS and W are different showing for the first time that the two states are very different in contrast to what was thought before.