Figure 3: The Central Autonomic Network (CAN).

The CAN involves all levels of the central neuraxis. At the cortical level the CAN includes the medial prefrontal cortex (PFC), anterior cingulate (CING), and insula (INS). Limbic system sites include the amygdala (AMY) and hippocampus (Hippo). Hypothalamic regions include the paraventricular nucleus (PVN) and the hypothalamic area controlling emotional responses (HACER). Midbrain components include the peri-aquaductal gray (PAG) and ventral tegmental area (VTA). Pontine components are the locus ceruleus (LC), parabrachial nucleus (PBN), and A5 noradrenergic cell groups. Among several medullary nuclei in the CAN there are the raphe serotonergic cell groups (Raphe), C1 noradrenergic neurons and respiration-related neurons (respiratory pattern generator (RPG), pre-Bötzinger (Pre-Bötz) complex, retrotrapezoid nucleus (RTN) in the rostral ventrolateral medulla (RVLM), A1 noradrenergic neurons in the caudal ventrolateral medulla (CVLM), the nucleus ambiguus (NA) the dorsal motor nucleus of the vagus nerve (DMNX), and the nucleus of the solitary tract (NTS), which is the main site of initial synapse formation in the baroreceptor and chemoreceptor reflexes. Other regions associated with the CAN include the circumventricular regions with an imperfect blood-brain barrier (e.g., the area postrema (AP) in the dorsal medulla). Five components of the autonomic nervous system are the enteric nervous system (ENS), which involves multiple neurotransmitter (Mult.), the parasympathetic nervous system (PNS) and sympathetic cholinergic system (SCS), which use acetylcholine (ACh) as the neurotransmitter, the sympathetic noradrenergic system (SNS), with norepinephrine (NE) the neurotransmitter, and the sympathetic adrenergic system (SAS), with epinephrine (EPI) the hormone. Neuronal clusters in regions of the CAN interact complexly, often in a bi-directional manner.