The suprachiasmatic nucleus (SCN) temporally organizes behavior in part by sustaining arousal during the wake period of the sleep/wake cycle to consolidate adaptive waking behavior. In this study, we demonstrate direct projections from the SCN, in both the rat and the human brains, to perikarya and proximal dendrites of two groups of posterior hypothalamic neurons with axonal projections that suggest they are important in the regulation of arousal, one producing hypocretins (HCT) and the other melanin-concentrating hormone (MCH). In addition, we demonstrate that both HCT and MCH-producing neurons are immunoreactive for glutamate (GLU). These observations support the hypothesis that direct projections from the SCN to the posterior hypothalamus mediate the arousal function of the circadian timing system.

Lesions in the septal region of the forebrain oftein produce a state of hyperirrilability in rats characterized chiefly by an exaggerated startle response lo tactile stimuli applied to the animal's back and intense and aggressive resistance to handling (Brad}' & Nauta, 1953). These behavioral manifestations (septal syndrome) tend to abate over a period of weeks (Brady & Nauta, 1955). The specific ncuroanatomic structures which must be destroyed to produce the septal syndrome have not been clearly specified (Harrison & Lyon). Nor do we understand the behavioral mechanisms which are altered by the lesions. Brady and Nauta (1953) reported that the lesions weakened a conditioned emotional response but had no effect on the acquisition of the CER. Results obtained by Tracy and Harrison suggest that septal lesions abolish lever pressing to escape an avcrsive noise stimulus but do not interfere with acquisition or retention of lever pressing for food reward with the same noise used as a discrimination stimulus (Tracy & Harrison, 1956). On the other hand, King (1958) found that rats with septal lesions learn conditioned avoidance responses in a double-grill box with even greater facility than normal controls. Subsequent lesions in the amygdala abolish the septal syndrome. Hunt (1957) has reported that rats with the septal syndrome are much more sensitive to the behavioral effects of meprobamate, alcohol, and mephenesin than are normal rats or rats with lesions in other parts of the brain.

In an investigation of rhinencephalic function, cats were taught a conditioned avoidance response (CAR) to an auditory CS in a double-grill shuttle box. Following separate, bilateral ablation of either cingulate cortex or septal region, or combined ablation of both septal region and hippocampal formation, retention of the CAR was impaired. Cortical control lesions did not affect CAR retention. As measured by ability to relearn the CAR, greatest impairment occurred with septal and combined septal-hippocampal lesions. Although some "septal" cats showed an irritability syndrome not unlike that seen in septal rats, this emotional disturbance was not correlated with the effect of septal ablation on the CAR.

Indolamine metabolism in the rat pineal is regulated by central influences mediated through the superior cervical sympathetics. The pineal stalk and medial habenular nucleus also have serotonin-containing cells and an innervation from the superior cervical ganglion (SCG). The present study was carried out to determine if the habenula and pineal stalk are similar to the pineal in certain aspects of indolamine metabolism. No diurnal rhythm in habenular serotonin content was observed, but ganglionectomy or decentralization of SCG results in a significant increase in habenular serotonin content. Unlike the pineal, the habenula and pineal stalk exhibit no rhythm in N-acetyltransferase (N-AT) activity; the activity of the enzyme in those tissues is comparable to low values of the diurnal rhythm in the pineal. N-AT activity in the pineal stalk and habenula is unaffected by sympathectomy. Similarly, there is little, if any, hydroxyindole-O-methyltransferase (HIOMT) activity in the pineal stalk and habenula; unlike the pineal, it is unaffected by continuous environmental lighting conditions or sympathectomy. These observations indicate that neither the pineal stalk nor the habenula represents a ‘deep’ pineal in the rat but that habenular indolamine metabolism is regulated by its peripheral sympathetic innervation.

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