IMR Press / JIN / Volume 21 / Issue 6 / DOI: 10.31083/j.jin2106163
Open Access Editorial
The Amygdala as a Mediator of Sleep and Emotion in Normal and Disordered States
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1 Sleep Research Lab, Center for Integrative Neuroscience and Inflammatory Disease, Pathology and Anatomy, Eastern Virginia Medical School, Norfolk, VA 23501, USA
*Correspondence: sanforld@evms.edu (Larry D. Sanford)
Academic Editor: Changjong Moon
J. Integr. Neurosci. 2022, 21(6), 163; https://doi.org/10.31083/j.jin2106163
Submitted: 21 July 2022 | Revised: 26 July 2022 | Accepted: 28 July 2022 | Published: 27 September 2022
(This article belongs to the Special Issue The Role of Amygdala in Regulating Sleep and Emotion)
Copyright: © 2022 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Sleep consists of two basic states, non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep, also known as slow wave sleep and paradoxical sleep, respectively. Good quality sleep may promote higher positive and lower negative affect [1]. Stressful and unpleasant emotional states can disturb sleep [2]. Further, sleep disturbances can reduce the ability to cope with stressful and emotional challenges appropriately, which may contribute to the development of transient emotional disturbances and persistent psychiatric disorders [3]. Traumatic life events virtually always produce at least temporary sleep disturbances that may include insomnia or subjective sleep problems [4], and the persistence of these disturbances may indicate the future development of emotional and cognitive disorders [5, 6, 7]. The bidirectional influences of emotion and sleep, and their relevance for both normal and disordered states, demonstrate the need to understand the nature and neural regulation of the relationship between emotion and sleep. Sleep disturbances are common in neuropsychiatric disorders. Although disturbances in both NREM and REM sleep occur, REM sleep, in particular, is thought to play an important role in the adaptive processing of emotionally significant memories in both humans [8, 9] and animals [10, 11]. Indeed, several authors have made suggestions consistent with this hypothesis, e.g., REM sleep weakens unwanted memory traces in the cortex [12], it aids in the processing of memory for trauma [13, 14], and may play a role in consolidating memories for aversive events and in “decoupling” them from their emotional charge [8, 9]. However, the relationship between emotion and REM sleep is complex. This is evidenced by the fact that alterations in REM sleep can become fear-conditioned and subject to extinction in much the same way that freezing and other behavioral and physiological responses can become fear-conditioned and extinguished [15, 16, 17]. Virtually all animal experimental behavioral assessments evoke emotional responses, and studies have repeatedly demonstrated that stressful experiences while awake can significantly influence subsequent sleep. REM sleep appears to be particularly susceptible to the effects of stress. Increases in REM sleep and changes in other sleep parameters have been reported for a great number of stressors, including avoidable footshock, restraint, water maze, exposure to novel objects, open field, ether exposure, cage change, and social stress (reviewed in [18]). Stressors such as inescapable footshock [19] can produce decreases in REM sleep that may relate to an animal’s inability to control or limit its exposure to stress [11]. Alterations in REM-sleep parameters may also be observed: REM sleep EEG theta (REM-θ, 5–8 Hz) amplitude may be reduced after social defeat [20] and alterations in theta amplitude have been linked to fear conditioning and extinction [21]. Thus, different emotional situations have the potential to produce different alterations in subsequent sleep amounts and archtitecture. The amygdala has a long-recognized role in emotion [22, 23, 24]. It is directly responsible for associating emotional significance with received information, as well as storing, coding, and recalling emotional memories. In addition, it interacts with the the prefrontal cortex, which is involved in working memory, motivation, planning, and in the diminishing of fear reactions. Additionally, the central nucleus of the amygdala plays a role in the modulation of autonomic phenomena including heart rate, blood pressure, and respiratory-activity patterning [25, 26, 27], particularly as related to stress [26]. The amygdala is an important mediator of the effects of emotion, fearful memories, and stress on arousal and sleep and also appears to function in the regulation of physiological sleep. The first suggestion that the amygdala might be involved in the actual regulation of sleep occurred in the early 1960s [28]. In the years since, studies by sleep researchers have reported on the role of the amygdala in regulating the EEG [29], ponto-geniculo-occipital (PGO) waves [29], REM sleep [30], and several studies have examined the influence of the amygdala on autonomic variables during wakefulness and sleep (e.g., [25, 31, 32]). Studies in narcoleptic dogs have also implicated the amygdala in cataplexy, which can be triggered by emotional stimuli [33, 34], and a finding of increased blood flow in the amygdala during REM sleep in humans [35] was interpreted as a possible link between emotionality controlled by the limbic system and dream content. Several studies have demonstrated effects of amygdala manipulations on spontaneous [36, 37, 38] and stress- and fear-induced [39, 40, 41] alterations in sleep. Recent work has shown that the amygdala also regulates REM sleep-specific acitivity that appears important for emotional learning. For example, REM-dependent physiological events, including θ coherence [42], REM-θ amplitude [21, 43], and phasic pontine-waves (P-waves, pontine component of PGO waves) [44] may be more accurate predictors of successful consolidation of fear memory than is the amount of REM sleep. Both REM-θ [43, 45] and P-waves [37, 46, 47] are regulated by the amygdala, which, along with the medial prefrontal cortex and hippocampus, exhibits coordinated θ activity associated with contextual fear conditioning [48]. Brief optic activation of the basolateral amygdala during REM sleep immediately reduced REM-θ without affecting overall amount of, and propensity for, sleep, whereas optic inhibition increased REM-θ [43, 45]. The reduction in REM-θ amplitude was associated with subsequent attenuated freezing and altered fear-conditioned REM-sleep responses [43]. Stimulation during NREM sleep did not affect any output measures, suggesting that the effects were REM-sleep specific. In summary, various lines of evidence have demonstrated that sleep and emotional disturbances, and their interactions, play roles in the development of a range of neuropsychiatric disorders as well as being continuing and distressing symptoms. The amygdala has been identified as a critical mediator of emotion and sleep, with significance for both normal function and psychopathology. It is also a clear target for understanding the neural mechanisms that link sleep and emotion. Delineating its role should provide significant insight into the regulation of sleep and emotion in both normal and disordered states.

Author Contributions

Not applicable.

Ethics Approval and Consent to Participate

Not applicable.

Acknowledgment

Not applicable.

Funding

This research received no external funding.

Conflict of Interest

The authors declare no conflict of interest. LS and LW are serving as the Guest editors of this journal. We declare that LS and LW had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to CM.

References
[1]
Sin NL, Almeida DM, Crain TL, Kossek EE, Berkman LF, Buxton OM. Bidirectional, Temporal Associations of Sleep with Positive Events, Affect, and Stressors in Daily Life Across a Week. Annals of Behavioral Medicine. 2017; 51: 402–415.
[2]
Harvey AG, Stinson K, Whitaker KL, Moskovitz D, Virk H. The Subjective Meaning of Sleep Quality: a Comparison of Individuals with and without Insomnia. Sleep. 2008; 31: 383–393.
[3]
Bryant RA, Creamer M, O’Donnell M, Silove D, McFarlane AC. Sleep Disturbance Immediately Prior to Trauma Predicts Subsequent Psychiatric Disorder. Sleep. 2010; 33: 69–74.
[4]
Lavie P. Sleep Disturbances in the Wake of Traumatic Events. New England Journal of Medicine. 2001; 345: 1825–1832.
[5]
Chang PP, Ford DE, Mead LA, Cooper-Patrick L, Klag MJ. Insomnia in Young Men and Subsequent Depression: the Johns Hopkins Precursors Study. American Journal of Epidemiology. 1997; 146: 105–114.
[6]
Koren D, Arnon I, Lavie P, Klein E. Sleep Complaints as Early Predictors of Posttraumatic Stress Disorder: a 1-Year Prospective Study of Injured Survivors of Motor Vehicle Accidents. American Journal of Psychiatry. 2002; 159: 855–857.
[7]
Neckelmann D, Mykletun A, Dahl AA. Chronic Insomnia as a Risk Factor for Developing Anxiety and Depression. Sleep. 2007; 30: 873–880.
[8]
Walker MP. The Role of Sleep in Cognition and Emotion. Annals of the New York Academy of Sciences. 2009; 1156: 168–197.
[9]
Walker MP, van der Helm E. Overnight therapy? The role of sleep in emotional brain processing. Psychological Bulletin. 2009; 135: 731–748.
[10]
Suchecki D, Tiba PA, Machado RB. REM Sleep Rebound as an Adaptive Response to Stressful Situations. Frontiers in Neurology. 2012; 3: 41.
[11]
Sanford LD, Yang L, Wellman LL, Liu X, Tang X. Differential Effects of Controllable and Uncontrollable Footshock Stress on Sleep in Mice. Sleep. 2010; 33: 621–630.
[12]
Crick F, Mitchison G. The function of dream sleep. Nature. 1983; 304: 111–114.
[13]
Mellman TA, Bustamante V, Fins AI, Pigeon WR, Nolan B. REM Sleep and the Early Development of Posttraumatic Stress Disorder. American Journal of Psychiatry. 2002; 159: 1696–1701.
[14]
Mellman TA, Pigeon WR, Nowell PD, Nolan B. Relationships between REM sleep findings and PTSD symptoms during the early aftermath of trauma. Journal of Traumatic Stress. 2007; 20: 893–901.
[15]
Sanford LD, Tang X, Ross RJ, Morrison AR. Influence of shock training and explicit fear-conditioned cues on sleep architecture in mice: strain comparison. Behavior Genetics. 2003; 33: 43–58.
[16]
Sanford LD, Yang L, Tang X. Influence of Contextual Fear on Sleep in Mice: a Strain Comparison. Sleep. 2003; 26: 527–540.
[17]
Wellman LL, Yang L, Tang X, Sanford LD. Contextual fear extinction eliminates sleep disturbances found following fear conditioning in rats. Sleep. 2008; 31: 1035–1042.
[18]
Pawlyk AC, Morrison AR, Ross RJ, Brennan FX. Stress-induced changes in sleep in rodents: Models and mechanisms. Neuroscience & Biobehavioral Reviews. 2008; 32: 99–117.
[19]
Adrien J, Dugovic C, Martin P. Sleep-wakefulness patterns in the helpless rat. Physiology & Behavior. 1991; 49: 257–262.
[20]
Matsuda Y, Ozawa N, Shinozaki T, Aoki K, Nihonmatsu-Kikuchi N, Shinba T, et al. Chronic antidepressant treatment rescues abnormally reduced REM sleep theta power in socially defeated rats. Scientific Reports. 2021; 11: 16713.
[21]
Boyce R, Glasgow SD, Williams S, Adamantidis A. Causal evidence for the role of REM sleep theta rhythm in contextual memory consolidation. Science. 2016; 352: 812–816.
[22]
Davis M. Animal models of anxiety based on classical conditioning: the conditioned emotional response (CER) and the fear-potentiated startle effect. Pharmacology & Therapeutics. 1990; 47: 147–165.
[23]
Davis M. The role of the amygdala in conditioned fear. In J. Aggleton (ed.) The Amygdala: Neurobiological Aspects of Emotion, Memory, and Mental Dysfunction (pp. 255–305). Wiley-Liss, Inc: New York. 1992.
[24]
LeDoux JE. Emotion Circuits in the Brain. Annual Review of Neuroscience. 2000; 23: 155–184.
[25]
Frysinger R, Zhang J, Harper R. Cardiovascular and respiratory relationships with neuronal discharge in the central nucleus of the amygdala during sleep-waking states. Sleep. 1988; 11: 317–332.
[26]
Roozendaal B, Koolhaas JM, Bohus B. Attenuated cardiovascular, neuroendocrine, and behavioral responses after a single footshock in central amygdaloid lesioned male rats. Physiology & Behavior. 1991; 50: 771–775.
[27]
Roozendaal B, Koolhaas JM, Bohus B. Central amygdala lesions affect behavioral and autonomic balance during stress in rats. Physiology & Behavior. 1991; 50: 777–781.
[28]
Adey WR, Kado RT, Rhodes JM. Sleep: Cortical and Subcortical Recordings in the Chimpanzee. Science. 1963; 141: 932–933.
[29]
Calvo JM, Badillo S, Morales-Ramirez M, Palacios-Salas P. The role of the temporal lobe amygdala in ponto-geniculo-occipital activity and sleep organization in cats. Brain Research. 1987; 403: 22–30.
[30]
Smith CT, Miskiman DE. Increases in paradoxical sleep as a result of amygdaloid stimulation. Physiology & Behavior. 1975; 15: 17–19.
[31]
Harper RM, Frysinger RC, Trelease RB, Marks JD. State-dependent alteration of respiratory cycle timing by stimulation of the central nucleus of the amygdala. Brain Research. 1984; 306: 1–8.
[32]
Zhang J, Harper RM, Frysinger RC. Respiratory modulation of neuronal discharge in the central nucleus of the amygdala during sleep and waking states. Experimental Neurology. 1986; 91: 193–207.
[33]
Mignot E, Guilleminault C, Bowersox S, Frusthofer B, Nishino S, Maddaluno J, et al. Central alpha 1 adrenoceptor subtypes in narcolepsy-cataplexy: a disorder of REM sleep. Brain Research. 1989; 490: 186–191.
[34]
Mignot E, Guilleminault C, Bowersox S, Rappaport A, Dement WC. Effect of alpha 1-adrenoceptors blockade with prazosin in canine narcolepsy. Brain Research. 1988; 444: 184–188.
[35]
Maquet P, Péters J, Aerts J, Delfiore G, Degueldre C, Luxen A, et al. Functional neuroanatomy of human rapid-eye-movement sleep and dreaming. Nature. 1996; 383: 163–166.
[36]
Sanford LD, Parris B, Tang X. GABAergic regulation of the central nucleus of the amygdala: implications for sleep control. Brain Research. 2002; 956: 276–284.
[37]
Sanford LD, Tejani-Butt SM, Ross RJ, Morrison AR. Amygdaloid control of alerting and behavioral arousal in rats: involvement of serotonergic mechanisms. Archives Italiennes de Biologie. 1995; 134: 81–99.
[38]
Sanford LD, Yang L, Liu X, Tang X. Effects of tetrodotoxin (TTX) inactivation of the central nucleus of the amygdala (CNA) on dark period sleep and activity. Brain Research. 2006; 1084: 80–88.
[39]
Wellman LL, Fitzpatrick ME, Hallum OY, Sutton AM, Williams BL, Sanford LD. Individual Differences in Animal Stress Models: Considering Resilience, Vulnerability, and the Amygdala in Mediating the Effects of Stress and Conditioned Fear on Sleep. Sleep. 2016; 39: 1293–1303.
[40]
Wellman LL, Fitzpatrick ME, Hallum OY, Sutton AM, Williams BL, Sanford LD. The basolateral amygdala can mediate the effects of fear memory on sleep independently of fear behavior and the peripheral stress response. Neurobiology of Learning and Memory. 2017; 137: 27–35.
[41]
Wellman LL, Fitzpatrick ME, Sutton AM, Williams BL, Machida M, Sanford LD. Antagonism of corticotropin releasing factor in the basolateral amygdala of resilient and vulnerable rats: Effects on fear-conditioned sleep, temperature and freezing. Hormones and Behavior. 2018; 100: 20–28.
[42]
Popa D, Duvarci S, Popescu AT, Léna C, Paré D. Coherent amygdalocortical theta promotes fear memory consolidation during paradoxical sleep. Proceedings of the National Academy of Sciences. 2010; 107: 6516–6519.
[43]
Machida M, Sweeten BLW, Adkins AM, Wellman LL, Sanford LD. The Basolateral Amygdala Mediates the Role of Rapid Eye Movement Sleep in Integrating Fear Memory Responses. Life. 2021; 12: 17.
[44]
Datta S, O’Malley MW. Fear Extinction Memory Consolidation Requires Potentiation of Pontine-Wave Activity during REM Sleep. Journal of Neuroscience. 2013; 33: 4561–4569.
[45]
Machida M, Sweeten BLW, Adkins AM, Wellman LL, Sanford LD. Basolateral Amygdala Regulates EEG Theta-activity during Rapid Eye Movement Sleep. Neuroscience. 2021; 468: 176–185.
[46]
Deboer T, Ross RJ, Morrison AR, Sanford LD. Electrical Stimulation of the Amygdala Increases the Amplitude of Elicited Ponto-geniculo-occipital Waves. Physiology & Behavior. 1999; 66: 119–124.
[47]
Deboer T, Sanford LD, Ross RJ, Morrison AR. Effects of electrical stimulation in the amygdala on ponto-geniculo-occipital waves in rats. Brain Research. 1998; 793: 305–310.
[48]
Seidenbecher T, Laxmi TR, Stork O, Pape H. Amygdalar and Hippocampal Theta Rhythm Synchronization during Fear Memory Retrieval. Science. 2003; 301: 846–850.
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