Wakefulness is a state that an animal can consciously sense internal drives and external stimuli and actively respond to environment. Fundamental endeavors such as finding food and avoiding predators require conscious and wakeful behaviors in order to improve chance of survival. Elementary CNS arousal drives shift between states of sleep and wakefulness, to orient an animal towards important stimuli and to maintain wakefulness in the absence of important external stimuli. Specific motives and incentives explain why an animal does one thing rather than another. Arousal is modulated by circadian, homeostatic, executive/cognitive, emotional, and environmental factors, which can be simply summarized as internal drives and environmental pressures. Both conceptually and experimentally, we know that an animal's level of arousal can be variable across minutes, days, seasons, and years. These variations are associated with behavioral characteristics such as mood, feelings, temperament, and overall cognition. While arousal's role in promoting sleep or wakefulness is one of its most obvious, and well-studied, effects on behavior, the more subtle shifts between quiet waking, alertness and attention are equally important, with potential clinical manifestations.

Medullary gigantocellular reticular nucleus (mGi) neurons have been ascribed a variety of behaviors, many of which may fall under the concepts of either arousal or motivation. Despite this, many details of the connectivity of mGi neurons, particularly in reference to those neurons with ascending axons, remain unknown. To provide a neuroanatomical and molecular characterization of these cells, with reference to arousal and level-setting systems, large medullary reticular neurons were characterized with retrograde dye techniques and with real-time reverse transcriptase PCR (RT-PCR) analyses of single-neuron mRNA expression in the mouse. We have shown that receptors consistent with participation in generalized arousal are expressed by single mGi neurons and that receptors from different families of arousal-related neurotransmitters are rarely coexpressed. Through retrograde labeling, we have shown that neurons with ascending axons and neurons with descending axons tend to form like-with-like clusters, a finding that is consistent across age and gender. In comparing the two groups of retrogradely labeled neurons in neonatal animals, those neurons with axons that ascend to the midbrain show markers for GABAergic or coincident GABAergic and glutamatergic function; in contrast, approximately 60% of the neurons with axons that descend to the spinal cord are glutamatergic. We discuss the mGi's relationship to the voluntary and emotional motor systems and speculate that neurons in the mGi may represent a mammalian analogue to Mauthner cells, with a separation of function for neurons with ascending and descending axons.

Whole-cell patch clamp recordings of the electrical activity of large medullary reticular formation neurons, in nucleus gigantocellularis, were performed under control conditions and under conditions of hypoxia or anoxia. Neurons were discovered whose activity was remarkably resilient during and after the reduction or loss of oxygen. Such cells may relate to the ability of the newborn brain to survive hypoxia/anoxia, and also may demonstrate the preservation of neurons involved in generalized CNS arousal, as would be appropriate for activating behavioral responses to the reduction or loss of oxygen.