The periaqueductal gray as a critical site to mediate reward seeking during predatory hunting

► Rostrolateral Periaqueductal Gray (rlPAG) lesions suppress insect hunting. ► The rlPAG projects to the orexinergic cell group in the lateral hypothalamus. ► The rlPAG influences the activation of the lateral orexinergic cell group. ► The rlPAG exerts a critical influence on reward seeking. Previous studies using morphine-treated dams reported a role for the rostral lateral periaqueductal gray (rlPAG) in the behavioral switching between nursing and insect hunting, likely to depend on an enhanced seeking response to the presence of an appetitive rewarding cue (i.e., the roach). To elucidate the neural mechanisms mediating such responses, in the present study, we first observed how the rlPAG influences predatory hunting in male rats. Our behavioral observations indicated that bilateral rlPAG NMDA lesions dramatically interfere with prey hunting, leaving the animal without chasing or attacking the prey, but do not seem to affect the general levels of arousal, locomotor activity and regular feeding. Next, using Phaseolus vulgaris-leucoagglutinin (PHA-L), we have reviewed the rlPAG connection pattern, and pointed out a particularly dense projection to the hypothalamic orexinergic cell group. Double labeled PHA-L and orexin sections showed an extensive overlap between PHA-L labeled fibers and orexin cells, revealing that both the medial/perifornical and lateral hypothalamic orexinergic cell groups receive a substantial innervation from the rlPAG. We have further observed that both the medial/perifornical and lateral hypothalamic orexinergic cell groups up-regulate Fos expression during prey hunting, and that rlPAG lesions blunted this Fos increase only in the lateral hypothalamic, but not in the medial/perifornical, orexinergic group, a finding supposedly associated with the lack of motivational drive to actively pursue the prey. Overall, the present results suggest that the rlPAG should exert a critical influence on reward seeking by activating the lateral hypothalamic orexinergic cell group.