Central mechanisms regulating coordinated cardiovascular and respiratory function during stress and arousal

Abstract

Actual or potentially threatening stimuli in the external environment (i.e., psychological stressors) trigger highly coordinated defensive behavioral responses that are accompanied by appropriate autonomic and respiratory changes. As discussed in this review, several brain regions and pathways have major roles in subserving the cardiovascular and respiratory responses to threatening stimuli, which may vary from relatively mild acute arousing stimuli to more prolonged life-threatening stimuli. One key region is the dorsomedial hypothalamus, which receives inputs from the cortex, amygdala, and other forebrain regions and which is critical for generating autonomic, respiratory, and neuroendocrine responses to psychological stressors. Recent studies suggest that the dorsomedial hypothalamus also receives an input from the dorsolateral column in the midbrain periaqueductal gray, which is another key region involved in the integration of stress-evoked cardiorespiratory responses. In addition, it has recently been shown that neurons in the midbrain colliculi can generate highly synchronized autonomic, respiratory, and somatomotor responses to visual, auditory, and somatosensory inputs. These collicular neurons may be part of a subcortical defense system that also includes the basal ganglia and which is well adapted to responding to threats that require an immediate stereotyped response that does not involve the cortex. The basal ganglia/colliculi system is phylogenetically ancient. In contrast, the defense system that includes the dorsomedial hypothalamus and cortex evolved at a later time, and appears to be better adapted to generating appropriate responses to more sustained threatening stimuli that involve cognitive appraisal. defensive behavior; sympathetic activity; respiratory activity; hypothalamus; midbrain; sympathetic premotor nuclei AN ANIMAL'S SURVIVAL is dependent on being able to respond appropriately to stressors, which can be categorized into two different groups: interoceptive (also-called physical) stressors and exteroceptive (also-called psychological) stressors (44,133). Physical stressors are those that directly threaten homeostasis, such as hypoxia, hemorrhage, or infection, whereas psychological stressors can be defined as actual or perceived threats in the external environment. Psychological stressors can be further subdivided into conditioned stressors (i.e., ones that are normally innocuous but which are perceived as threatening because of previous experiences) or unconditioned stressors (i.e., ones that are intrinsically threatening, such as the sight, sound, or odor of a predator). Physical and psychological stressors activate different populations of neurons in the brain (44,63,102). Similarly, there is evidence that the autonomic responses to conditioned and unconditioned psychological stressors are also mediated by different pathways in the brain (62). In this review, which is based on my 2013 Carl Ludwig Distinguished Lecture to the American Physiological Society, I consider the brain mec...

Cardiovascular and autonomic reactivity to psychological stress: Neurophysiological substrates and links to cardiovascular disease

“…Moreover, they demonstrated that vmPFC and ACC associations with HR reactivity were mediated (statistically accounted for) by concurrent changes in the PAG and thalamus, thus potentially defining a forebrain-to-subcortical pathway for stressor-evoked cardiovascular (HR) reactivity. These findings agree with neuroanatomical tracing work in primates and other nonhuman animal models demonstrating projections from the medial prefrontal cortex to the PAG and hypothalamus (Bandler et al, 2000; Dampney, 2015), as well as primate anatomical work on the coritical control of the adrenal medulla (Dum et al, 2016). As noted above, this particular line of work was also extended recently to define a multivariate pattern of neural activity encompassing the vmPFC and other networked limbic regions that reliably predicted individual differences in stressor-evoked HR and sympathetic nervous system reactivity (skin conductance) using multivariate methods (Eisenbarth, Chang, & Wager, 2016).…”

“…The brain has long been implicated in the control of cardiovascular function, particularly in linking stressful experiences to cardiovascular changes associated with clinical events and disease pathophysiology (for reviews see Dampney, 2015; Lane et al., 2009a; 2009b; Palma & Benarroch, 2014; Taggart et al, 2016; Esler, 2017). For example, Cannon originally proposed that intense emotions, such as fright, were generated in the brain and triggered peripheral physiological responses that could end one’s life in “voodoo death” (Cannon, 1928; 1942).…”

Arcuate neuropeptide Y inhibits sympathetic nerve activity via multiple neuropathways

“…Previous studies have documented that the DMH is an important node in sympathoexcitatory responses, in particular following psychological stress (for reviews, see refs. 48,52,53). A key component of this stress-induced descending pathway includes the RVLM (33,54,55).…”

Limbic modulation of the autonomic nervous system

“…However, the physiological interactions between higher cognitive brain structures to the PAG have not been demonstrated. Although, there are no monosynaptic connections between the hippocampus and PAG, forebrain structures have the capacity to engage the brainstem through a variety of relay nuclei (Dampney, 2015). Thus, it was hypothesised that the hippocampus-amygdala axis may be a circuit through which motor and autonomic changes could occur.…”

“…Based on the ability to modulate cardiorespiratory activities, the amygdala is part of the proposed central autonomic network (Dampney et al, 2002;Dampney, 2015). This argument is supported by projections from the CeA to the dorsomedial hypothalamus (Ono et al, 1985), sympathetic preganglionic neurones in the nucleus ambiguus and rostral ventrolateral medulla (Jongen- Relo and Amaral, 1998;Oka et al, 2008), and parasympathetic neurones in the dorsal motor nucleus of the vagus (Takeuchi et al, 1983).…”