Fig. 1.

(A) Simplified schematic representation of ascending arousal regulatory pathways. Norepinephrine-containing systems (NE, also known as noradrenergic) tend to emphasize projections to the more posterior cerebral cortex and to support sensory alertness. Dopaminergic systems (DA) tend to project more strongly to anterior, frontal cortex and to foster directed motor acts. Serotonergic (5HT) neurons project preferentially to limbic cortex and hypothalamus and are involved in emotional behaviors and autonomic controls. Cholinergic neurons (ACh) in the basal forebrain support arousal by their widespread projections across the cerebral cortex. Histamine-producing neurons (HA) likewise have extremely widespread projections that actually originate in the hypothalamus and are strongly associated with increased CNS arousal. (B) Simplified schematic representation of descending arousal regulatory pathways. Lateral hypothalamic area (LHA) hypocretin/orexin neurons project to monoamine-expressing cell groups in the lower brainstem and even the spinal cord. Neurons that express oxytocin (OT) and arginine vasopressin (AVP) in the parvocellular portion of the paraventricular hypothalamic nucleus (PVNp) control autonomic arousal through the lower brainstem and spinal cord and affect EEG arousal through projections to locus coeruleus. Hypothalamic neurons containing histamine (HA) in the tuberomammillary nucleus (TMN) have widespread projections and receive inputs from a biological clock, the suprachiasmatic nucleus (SCN). Preoptic area (POA) neurons have descending axons that affect sleep and autonomic physiology. Adapted from ref. 1.