Table 1.

Limbic brainstem nuclei key characteristics.

Nuclei	Cell Type	Key points
Nucleus tractus solitarius (NTS) Owen et al. (2008), Weinstein et al. (2015), and George et al. (2019)	Multiple	The Nucleus Solitarius is the major afferent nuclei for vagal visceral sensory fibers and the subsequent relay of that information to other brainstem centers (notably the LC and DRN) and eventually higher cortical centers. It is directly involved in the vagal nerve stimulation pathway.
Locus coeruleus (LC) Levy et al. (1987), Sillery et al. (2005), and Adell, 2015; Sims-Williams et al. (2017)	Norepinephrine	The Locus Coeruleus-Norepinephrine (LC-NE) system plays a key role in arousal, attention, and stress responses. The LC is the sole source of NE to cortical circuits. The LC-NE system is greatly impacted in neurodegenerative diseases such as Parkinson's Disease, which is theorized to result from abnormal signaling leading to cognitive and motor manifestations of the disease. It also received direct input from the NTS and has been shown to be essential for the efficacy of VNS in epilepsy.
Dorsal raphe nucleus (DRN) Arias-Carrión and Pöppel (2007) and Settell et al. (2017)	Serotonin	Major source of serotonin that project to the forebrain. Receives projections from the LC and, some argue, from the NTS as well. Lesions in rats abolish the efficacy of VNS for epilepsy.
Periaqueductal Grey (PAG) Fischl et al. (2002); Angeles Fernández-Gil et al. (2010), and Venkatraman et al. (2017)	Multiple	The PAG is a key structure in pain modulation, sympathetic responses, and the learning of defensive and aversive behaviors. As a result, the PAG is important in everyday interactions with the environment and human responses to adversive stimuli. The PAG is thought to contribute to defensive behaviors, panic attacks, anxiety, depression, and migraines.
Ventral tegmental area (VTA) Angeles Fernández-Gil et al. (2010), Ogisu et al. (2013), and Venkatraman et al. (2017)	Dopamine	Processing of reward and aversive experiences, major source of dopamine for mesocortical-limbic pathway.