Orexinergic systems responsible for the mechanisms of involved in the initiation and selection of emotional motor behaviors.

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Orexinergic neurons in the perifornical lateral hypothalamus project to structures of the midbrain, including the substantia nigra and the mesopontine tegmentum. The areas contain the mesencephalic locomotor region (MLR), and the pedunculopontine and laterodorsal tegmental nuclei (PPN/LDT) which regulate atonia during rapid eye movement (REM) sleep. Deficiencies of the orexinergic system result in narcolepsy, suggesting that these projections are concerned with switching between locomotor movements and muscular atonia. The present study characterizes the role of these orexinergic projections to the midbrain. In decerebrate cats, injecting orexin-A (60μM to 1.0mM, 0.20 to 0.25μ1) into the MLR reduced the intensity of the electrical stimulation required to induce locomotion on a treadmill (4 cats) or even elicit locomotor movements without electrical stimulation. On the other hand, when orexin was injected into either the PPN or the substantia nigra pars reticulata (SNr), an increased stimulus intensity at the PPN was required to induce muscle atonia. The effects of orexin on the PPN and the SNr were reversed by subsequently injecting bicuculline (5mM, 0.20 to 0.25μl), a GABA_A receptor antagonist, into the PPN. These findings indicate that excitatory orexinergic drive could maintain a higher level of locomotor activity by increasing the excitability of neurons in the MLR, while enhancing GABAergic effects on presumably cholinergic PPN neurons, to suppress muscle atonia.We conclude that orexinergic projections from the hypothalamus to the midbrain play an important role in regulating motor behavior and controlling postural muscle tone and locomotor movements when awake and during sleep. Furthermore, as the excitability is attenuated in the absence of orexin, signals to the midbrain may induce locomotor behavior when the orexinergic system functions normally but elicit atonia or narcolepsy when the orexinergic function is disturbed.