“The activation of these [LC] neurons in Hypercapnia, generally associated with increased apprehension in man, is consistent with the notion that the LC may serve as an alarm system in the brain.” Brain Res. 1981 Oct 19;222(2):373-81. doi: 10.1016/0006-8993(81)91040-4. Hypercapnia and hypoxia: chemoreceptor-mediated control of locus coeruleus neurons and splanchnic, sympathetic nerves M Elam, T Yao, P Thorén, T H Svensson
Threats or stressors activate brainstem nuclei , particularly the Locus Coeruleus [LC]. The LC has widespread [NE] projections throughout the central nervous system thought to primarily function to globally modulate behaviour and arousal states…….LC nuclei innervate the spinal cord, the brain stem, cerebellum, hypothalamus, the thalamic relay nuclei, the amygdala, the basal telencephalon, and the cortex. The norepinephrine[NE] from the LC has an excitatory effect on most of the brain, mediating arousal and priming the brain’s neurons to be activated by stimuli.
Threats or stressors activate brainstem nuclei, particularly the locus coeruleus (LC). The LC has widespread norepinephrine (NE) projections throughout the central nervous system (CNS) thought to primarily function to globally modulate behavior and arousal states. NE has myriad central functions including regulation of CNS cells and circuits (O’Donnell et al., 2012). The LC is the major producer of NE in the CNS and LC activation produces NE release throughout the cortex, acting as a single global regulator (O’Donnell et al., 2012). Tonic, continuous activity of the LC is low during sleep, intermediate during active wake and high in states of distress or anxiety (Atzori et al., 2016). Acute threats also engage the sympathetic nervous system for the behavioral ‘fight or flight’ response (hypothalamus–pituitary–adrenal (HPA) axis), which elevates circulating glucocorticoids for a coordinated physiological and behavioral response (Charmandari et al., 2005) (Figure 1). A ‘normal’ or adaptive response to threat can present as freezing or motor arrest, often used as a primary proxy of fear in rodents or somatomotor agitation or exertion. Both responses are coupled with increased vigilance and arousal, critical for the alerting, orienting and fear learning functions required in a dangerous or uncertain environment (Cardinal et al., 2002; Sara and Bouret, 2012)…………..The LC is critically placed to modulate both ascending visceral feedback and descending cortical cognitive processing to mediate both psychological and physiological operations (Berntson et al., 2003). While threat or perceived stress broadly increases sympathetic tone and HPA axis activation (Carrasco and Van de Kar, 2003; Makino et al., 2002), it also recruits LC activity and NE release throughout the CNS. Direction of attention and memory formation, particularly for threat-related stimuli and events, are both under tight regulation by the LC. Indeed the LC responds rapidly to a range of threatening stimuli, including even the mere anticipation of threat (Baas et al., 2006; Clewett et al., 2018), subliminal fear (Liddell et al., 2005) or perceived stress (van Marle et al., 2010) and the broader LC-NE system governs an ‘alarm system’ response to stress (Lanius et al., 2017) across species.
So, it seems that both HYPERCAPNIA and perceived threats will engage the same systems of the brain and body. This makes it hard to tease them apart.