Abstract
Fear conditioning alters sleep, with the most consistent effect being significant reductions in rapid eye movement sleep (REM). DBA/2 (D2) mice show behavioral signs of anxiety, respond greater to shock training, and potentially behave differently in cued and contextual fear, raising the question of how fear conditioning would affect their sleep. D2 mice were implanted to record sleep via telemetry. After baseline sleep recording, groups of D2 mice were trained in cued (15 tone–shock pairings) and contextual (15 non-cued shocks) fear on 4 consecutive days. Cue and context control mice were given identical training but were never presented with shock. Sleep was recorded after shock training and after presentation of cue or context alone. Shock training produced selective suppression of REM. On the day after shock training was completed, light period sleep was significantly altered in mice in the cued fear group, but not in the contextual fear group. Subsequent presentation of fearful cues and re-exposure to the fearful contexts also produced significant reductions in REM. The effects of fear conditioning on sleep in D2 mice and other mouse strains and the differential effects of cued and contextual fear on sleep are discussed.
Zusammenfassung
Konditionierung von Angst verändert den Schlaf. Dabei ist der am deutlichsten konsistente Effekt eine signifikante Reduktion des REM(„rapid eye movement“)-Schlafs. DBA/2(D2)-Mäuse zeigen Auswirkungen Anspannung, stärkere Reaktionen auf Schocktraining und potenziell verändertes Verhalten nach Konditionierung von auslöser- und kontextbedingter Angst. Daraus ergibt sich die Frage, wie die Konditionierung von Angst den Schlaf beeinflusst. D2-Mäusen wurden Elektroden für die telemetrische Polysomnographie implantiert. Nach einer Basisableitung wurden Gruppen von D2-Mäusen an 4 konsekutiven Tagen auslöser- (15 Schock-Ton-Reize) und kontextbedingten (15 Schockreize ohne Ton) Angst induzierenden Situationen ausgesetzt. Die Mäuse in den Kontrollgruppen wurden genauso behandelt, sie erhielten nur keine Schockreize. In den danach abgeleiteten Polysomnographien zeigte sich nach Schockexposition eine selektive REM-Unterdrückung. Am Tag nach Beendigung des Schocktrainings war die Leichtschlafphase bei den Mäusen mit auslöserbedingter Angst signifikant verändert, bei den Mäusen mit kontextbedingter Angst dagegen nicht. Eine spätere erneute Präsentation der angstbesetzten Auslöser und eine Reexposition mit dem angstbesetztem Kontext führten ebenfalls zu einer deutlichen Abnahme der REM-Phasen. Diskutiert werden die Auswirkungen der Konditionierung von Angst auf den Schlaf von Mäusen (D2 und andere Stämme) sowie die differenziellen Effekte von auslöser- und kontextbedingter Angst auf den Schlaf.
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References
Adell A, Trullas R, Gelpi E (1988) Time course of changes in serotonin and noradrenaline in rat brain after predictable or unpredictable shock. Brain Res 459:54–59
Adrien J, Dugovic C, Martin P (1991) Sleep-wakefulness patterns in the helpless rat. Physiol Behav 49:257–262
Belzung C, Griebel G (2001) Measuring normal and pathological anxiety-like behaviour in mice: a review. Behav Brain Res 125:141–149
Cabib S, Puglisi-Allegra S, Ventura R (2002) The contribution of comparative studies in inbred strains of mice to the understanding of the hyperactive phenotype. Behav Brain Res 130:103–109
Charney D, Deutch A (1996) A functional neuroanatomy of anxiety and fear: implications for the pathophysiology and treatment of anxiety disorders. Critical Rev Neurobiol 10:419–446
Crawley JN (1999) Behavioral phenotyping of transgenic and knockout mice: experimental design and evaluation of general health, sensory functions, motor abilities, and specific behavioral tests. Brain Res 835:18–26
Crawley JN, Davis LG (1982) Baseline exploratory activity predicts anxiolytic responsiveness to diazepam in five mouse strains. Brain Res Bull 8:609–612
Davis M (1990) Animal models of anxiety based on classical conditioning: the conditioned emotional response (CER) and the fear-potentiated startle effect. Pharmaco Therapeut 47:147–165
Davis M (1992) The role of the amygdala in fear and anxiety. Ann Rev Neurosci 15:353–375
Davis M, Whalen PJ (2001) The amygdala: vigilance and emotion. Mol Psychiatry 6:13–34
Desmedt A, Garcia R, Jaffard R (1998) Differential modulation of changes in hippocampal-septal synaptic excitability by the amygdala as a function of either elemental or contextual fear conditioning in mice. J Neurosci 18:480–487
Falls W, Carlson S, Turner J et al (1997) Fear-potentiated startle in two strains of inbred mice. Behav Neurosci 111 855–861
Franken P, Malafosse A, Tafti M (1999) Genetic determinants of sleep regulation in inbred mice. Sleep 22:155–169
Franken P, Malafosse A, Tafti M (1998) Genetic variation in EEG activity during sleep in inbred mice. Am J Physiol 275:R1127–1137
Gorman JM, Kent JM, Sullivan GM et al (2000) Neuroanatomical hypothesis of panic disorder, revised. Am J Psychiatry 157:493–505
Grillon C, Southwick SM, Charney DS (1996) The psychobiological basis of posttraumatic stress disorder. Mol Psychiatry 1:278–297
Holmes A, Wrenn CC, Harris AP et al (2002) Behavioral profiles of inbred strains on novel olfactory, spatial and emotional tests for reference memory in mice. Genes Brain Behav 1:55–69
Jha SK, Brennan FX, Pawlyk AC et al (2005) REM sleep: a sensitive index of fear conditioning in rats. Eur J Neurosci 21:1077–1080
Lavie P (2001) Sleep disturbances in the wake of traumatic events. N Engl J Med 345:1825–1832
Ledoux J (2003) The emotional brain, fear, and the amygdala. Cell Mol Neurobiol 23:727–738
Ledoux JE (2000) Emotion circuits in the brain. Annu Rev Neurosci 23:155–184
Liu X, Wellman LL, Yang L et al (2011) Antagonizing corticotropin-releasing factor in the central nucleus of the amygdala attenuates fear-induced reductions in sleep but not freezing. Sleep 34:1539–1549
Liu X, Yang L, Wellman LL et al (2009) GABAergic antagonism of the central nucleus of the amygdala attenuates reductions in rapid eye movement sleep after inescapable footshock stress. Sleep 32:888–896
Machida M, Yang L, Wellman LL et al (2012) Effects of stressor predictability on escape learning and sleep in mice. Sleep (In Press)
Mccaughran JA Jr, Bell J 3rd, Hitzemann RJ (2000) Fear-potentiated startle response in mice: genetic analysis of the C57BL/6J and DBA/2J intercross. Pharmacol Biochem Behav 65:301–312
Mellman TA, Bustamante V, Fins AI et al (2002) REM sleep and the early development of posttraumatic stress disorder. Am J Psychiatry 159:1696–1701
Mellman TA, Pigeon WR, Nowell PD et al (2007) Relationships between REM sleep findings and PTSD symptoms during the early aftermath of trauma. J Trauma Stress 20:893–901
Neylan TC, Otte C, Yehuda R et al (2006) Neuroendocrine regulation of sleep disturbances in PTSD. Ann N Y Acad Sci 1071:203–215
Nguyen PV, Abel T, Kandel ER et al (2000) Strain-dependent differences in LTP and hippocampus-dependent memory in inbred mice. Learn Mem 7:170–179
Nie T, Abel T (2001) Fear conditioning in inbred mouse strains: an analysis of the time course of memory. Behav Neurosci 115:951–956
Pawlyk AC, Jha SK, Brennan FX et al (2005) A rodent model of sleep disturbances in posttraumatic stress disorder: the role of context after fear conditioning. Biol Psychiatry 57:268–277
Paylor R, Baskall L, Wehner J (1993) Behavioral dissociations between C57BL/6 and DBA/2 mice on learning and memory tasks: a hippocampal-dysfunction hypothesis. Psychobiology 21:11–26
Paylor R, Tracy R, Wehner J et al (1994) DBA/2 and C57BL/6 mice differ in contextual fear but not auditory fear conditioning Behav Neurosci 108:810–817
Phillips RG, Ledoux JE (1992) Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning. Behav Neurosci 106:274–285
Ross RJ, Ball WA, Dinges DF et al (1994) Rapid eye movement sleep disturbance in posttraumatic stress disorder. Biol Psychiatry 35:195–202
Ryabinin AE, Wang YM, Finn DA (1999) Different levels of Fos immunoreactivity after repeated handling and injection stress in two inbred strains of mice. Pharmacol Biochem Behav 63:143–151
Sanford L, Yang L, Tang X (2003) Influence of contextual fear on sleep architecture in mice: a strain comparison. Sleep 26:527–540
Sanford LD, Fang J, Tang X (2003) Sleep after differing amounts of conditioned fear training in BALB/cJ mice. Behavioural Brain Research 147:193–202
Sanford LD, Silvestri AJ, Ross RJ et al (2001) Influence of fear conditioning on elicited ponto-geniculo-occipital waves and rapid eye movement sleep. Arch Ital Biol 139:169–183
Sanford LD, Tang X, Ross RJ et al (2003) Influence of shock training and explicit fear-conditioned cues on sleep architecture in mice: strain comparison. Behav Genet 33:43–58
Sanford LD, Yang L, Wellman LL et al (2010) Differential effects of controllable and uncontrollable footshock stress on sleep in mice. Sleep 33:621–630
Shalev AY (2000) Biological responses to disasters. Psychiatric Quarterly 71:277–288
Shalev AY, Ragel-Fuchs Y, Pitman RK (1992) Conditioned fear and psychological trauma. Biol Psychiatry 31:863–865
Stiedl O, Radulovic J, Lohmann R et al (1999) Strain and substrain differences in context- and tone-dependent fear conditioning of inbred mice. Behav Brain Res 104:1–12
Tang X, Orchard SM, Sanford LD (2002) Home cage activity and behavioral performance in inbred and hybrid mice. Behav Brain Res 136:555–569
Tang X, Sanford LD (2002) Telemetric recording of sleep and home cage activity in mice. Sleep 25:691–699
Wehner JM, Radcliffe RA, Rosmann ST et al (1997) Quantitative trait locus analysis of contextual fear conditioning in mice. Nat Genet 17:331–334
Wellman LL, Ambrozewicz MA, Yang L et al (2013) Basolateral amygdala and the regulation of fear conditioned changes in sleep: role of corticotropin releasing factor. Sleep 36:471–480
Yang L, Tang X, Wellman LL et al (2009) Corticotropin releasing factor (CRF) modulates fear-induced alterations in sleep in mice. Brain Res 1276:112–122
Yang L, Wellman LL, Ambrozewicz MA et al (2011) Effects of stressor predictability and controllability on sleep, temperature, and fear behavior in mice. Sleep 34:759–771
Acknowledgements
This work was supported by NIH research grants MH64827 and MH61716. We would like to thank Stuart M. Orchard for his technical assistance on this study.
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The corresponding author states that there are no conflicts of interest.
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Yang, L., Tang, X. & Sanford, L. Effects of cued and contextual fear on sleep in DBA/2J mice. Somnologie 17, 80–89 (2013). https://doi.org/10.1007/s11818-013-0610-4
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DOI: https://doi.org/10.1007/s11818-013-0610-4