Single-unit response of noradrenergic neurons in the locus coeruleus of freely moving cats. I. Acutely presented stressful and nonstressful stimuli
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The present experiment was designed to explore the stress-relatedness of activity in noradrenergic neurons of the locus coeruleus (LC) of behaving cats. A stressor was defined as a stimulus that elicited a significant sympathoadrenal activation as measured by plasma norepinephrine level and heart rate. According to this definition, exposure to 15 min of 100 dB white noise or 15 min of restraint was stressful in cats. In contrast, exposure to inaccessible rats for 15 min was behaviorally activating but nonstressful. The single-unit activity of noradrenergic neurons in the LC of behaving cats was examined under these conditions. The stressful stimuli elicited a significant increase in LC neuronal activity for the entire 15 min stressor duration, whereas the behaviorally activating but nonstressful stimulus elicited no significant change in the activity of these neurons. These results provide evidence that behavioral activation per se is not sufficient to evoke a tonic activation of these neurons. Rather, these data support the hypothesis that the LC is involved in the CNS response to stress and provide additional evidence that the activity of LC noradrenergic neurons increases in association with sympathoadrenal activation.
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Studies in animals show that early stressors lead to increased activity of the locus coeruleus with resultant increased release of nor-epinephrine in the brain.
“Studies in animals show that early stressors lead to increased activity of the locus coeruleus with resultant increased release of nor-epinephrine in the brain (Abercrombie and Jacobs 1987).”
From The enduring effects of abuse and related adverse experiences in childhood: A convergence of evidence from neurobiology and epidemiology (2006) · cites this paper as Abercrombie and Jacobs 1987
The Summary (p. 2843) reports increased locus coeruleus activity during acute stress in freely moving cats. The paper does not study early-life stressors or measure norepinephrine release in the brain; its introduction describes earlier evidence as indirect measures of central norepinephrine utilization. (LLM, conf=0.88)
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Cites
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ResultCatecholamine‐containing neurons of the nucleus locus coeruleus in the cat
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“These observations have led to the proposal that the LC is a central analog of peripheral sympathetic ganglia (Amaral and Sinnamon, 1977; Aghajanian and VanderMaelen, 1982; Elam et al., 1986; Reiner, 1986).”
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ResultSelf-citationACTIVITY OF NOREPINEPHRINE-CONTAINING LOCUS COERULEUS NEURONS IN THE UNANESTHETIZED SQUIRREL MONKEY
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“The role of the noradrenergic system in anxiety is well documented (Charney and Redmond, 1983; Abercrombie and Jacobs, 1987a,b; Nukina et al., 1987; Tejani-Butt et al., 1994; McEwen and Sapolsky, 1995; Quirarte et al., 1997; Arnsten, 1998), and the role of the a2-ARs in anxiety has been examined…”
BackgroundBrebner, K., Hayley, S., Zacharko, R., Merali, Z., & Anisman, H. (2000) · Neuropsychopharmacology · doi:10.1016/s0893-133x(99)00166-9 · Cited by 214 · see citing works
Release of neurotransmitters in the locus coeruleus.
Singewald, N., & Philippu, A. (1998) · Progress in neurobiology · doi:10.1016/s0301-0082(98)00039-2 · Cited by 213 · see citing works
Phasic locus coeruleus activity regulates cortical encoding of salience information
Vazey, E. M., Moorman, D. E., & Aston‐Jones, G. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1803716115 · Cited by 241 · see citing works
Locus coeruleus cell loss in the aging human brain: A non‐random process
Manaye, K., McIntire, D., Mann, D. M. A., & German, D. (1995) · The Journal of comparative neurology · doi:10.1002/cne.903580105 · Cited by 212 · see citing works
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Animal models of parkinsonism using selective neurotoxins: clinical and basic implications.
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Ross, J. A., & Bockstaele, E. J. V. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.601519 · Cited by 223 · see citing works
“LC activation during attention orientation by salient somatosensory stimuli triggers rapid phasic LC responses offset by ∼20ms (110), while novel visual stimuli elicit a phasic LC response occurs over a timescale of 50–100ms (118, 208, 209).”
BackgroundResponses of primate locus coeruleus neurons to simple and complex sensory stimuli
Grant, S. J., Aston‐Jones, G., & Redmond, D. E. (1988) · Brain Research Bulletin · doi:10.1016/0361-9230(88)90152-9 · Cited by 170 · see citing works
Abercrombie, E., & Jacobs, B. (1987) · Journal of Neuroscience · doi:10.1523/jneurosci.07-09-02844.1987 · Cited by 184 · see citing works
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Afferents to basal forebrain cholinergic projection neurons: an update.
Záborszky, L., Cullinan, W., & Braun, A. (1991) · Advances in Experimental Medicine and Biology · doi:10.1007/978-1-4757-0145-6_2 · Cited by 173 · see citing works
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Topographic architecture of stress-related pathways targeting the noradrenergic locus coeruleus
Bockstaele, E. J. V., Bajic, D., Proudfit, H. K., & Valentino, R. J. (2001) · Physiology & Behavior · doi:10.1016/s0031-9384(01)00448-6 · Cited by 175 · see citing works
Berridge, C. W., & Abercrombie, E. D. (1999) · Neuroscience · doi:10.1016/s0306-4522(99)00276-6 · Cited by 171 · see citing works
Self-citationInduction of c-fos mRNA in rat brain by conditioned and unconditioned stressors
Smith, M. A., Banerjee, S., Gold, P. W., & Glowa, J. R. (1992) · Brain Research · doi:10.1016/0006-8993(92)90240-a · Cited by 173 · see citing works
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Dual Effects of d-Amphetamine on Dopamine Neurons Mediated by Dopamine and Nondopamine Receptors
Shi, W.-X., Pun, C.-L., Zhang, X.-X., Jones, M. D., & Bunney, B. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-09-03504.2000 · Cited by 159 · see citing works
Sensitivity of Locus Ceruleus Neurons to Reward Value for Goal-Directed Actions
Bouret, S., & Richmond, B. J. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.4553-14.2015 · Cited by 163 · see citing works
“What process does LC activation subserve? Activation of LC neurons has long been associated with salient events and the associated orienting responses (Foote et al., 1980; Aston-Jones and Bloom, 1981; Abercrombie and Jacobs, 1987; Berridge and Waterhouse, 2003; Bouret and Richmond, 2009; Sara and Bouret, 2012).”
BackgroundBuffalari, D., & Grace, A. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.2007-07.2007 · Cited by 157 · see citing works
“LC neurons are activated by stressful stimuli (Rasmussen et al., 1986; Abercrombie and Jacobs, 1987; Grant et al., 1988; Aston-Jones et al., 1991), and presumably mediate the stress-induced increase in NE in the BLA.”
BackgroundCentral noradrenergic neurones and stress
Stanford, S. C. (1995) · Pharmacology & Therapeutics · doi:10.1016/0163-7258(95)02010-1 · Cited by 152 · see citing works
Radley, J. J., Williams, B., & Sawchenko, P. E. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.0552-08.2008 · Cited by 148 · see citing works
“Electrophysiologic activity and immediate-early gene responses of LC neurons are enhanced by exposure to a variety of acute emotional stressors, as is NE release in mPFC (Abercrombie and Jacobs, 1987; Ceccatelli et al., 1989; Cullinan et al., 1995; Palkovits et al., 1997; Passerin et al., 2000).”
BackgroundStamp, J. A., & Herbert, J. (1999) · Neuroscience · doi:10.1016/s0306-4522(99)00368-1 · Cited by 145 · see citing works
Neurobiological factors in personality and depression
Depue, R. (1995) · European Journal of Personality · doi:10.1002/per.2410090509 · Cited by 152 · see citing works
A function for REM sleep: regulation of noradrenergic receptor sensitivity.
Siegel, J. M., & Rogawski, M. A. (1988) · Brain Research · doi:10.1016/0165-0173(88)90007-0 · Cited by 151 · see citing works
Gasser, P., Lowry, C., & Orchinik, M. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.0570-06.2006 · Cited by 145 · see citing works
“Both of these groups of neurons are activated during stress (Abercrombie and Jacobs, 1987; Daugherty et al., 2001) and are proposed to contribute to the regulation of stress responses (Graeff et al.”
BackgroundNeuropeptide and small transmitter coexistence: Fundamental studies and relevance to mental illness
Hökfelt, T., Barde, S., Xu, Z.-Q. D., Kuteeva, E., Rüegg, J., Le Maitre, E., Risling, M., Kehr, J., Ihnatko, R., Theodorsson, E., et al. (2018) · Frontiers in Neural Circuits · doi:10.3389/fncir.2018.00106 · Cited by 139 · see citing works
“…the LC: stress increases NA turnover, as well as tyrosine hydroxylase activity and transcription in the LC (Korf et al., 1973; Zigmond et al., 1974; Abercrombie and Jacobs, 1987; Komori et al., 1990; Smith et al., 1991; Melia et al., 1992; Aston-Jones et al., 1996; Rusnak et al., 1998; Chang et…”
BackgroundLechner, S. M., Curtis, A. L., Brons, R., & Valentino, R. J. (1997) · Brain Research · doi:10.1016/s0006-8993(97)00116-9 · Cited by 137 · see citing works
Tornatzky, W., & Miczek, K. A. (1994) · Psychopharmacology · doi:10.1007/bf02245339 · Cited by 168 · see citing works
Mejias-Aponte, C., Drouin, C., & Aston-Jones, G. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.4632-08.2009 · Cited by 137 · see citing works
“Physiological stressors such as cardiovascular, osmotic and immune challenges, as well as psychological stressors including restraint and intermittent footshock, activate these adrenergic cells (Abercrombie and Jacobs, 1987; Morilak et al., 1987; Sawchenko et al., 2000).”
BackgroundAbercrombie, E. D., & Zigmond, M. J. (1989) · Journal of Neuroscience · doi:10.1523/jneurosci.09-11-04062.1989 · Cited by 125 · see citing works
Self-citationRincón‐Cortés, M., & Sullivan, R. M. (2014) · Frontiers in Endocrinology · doi:10.3389/fendo.2014.00033 · Cited by 138 · see citing works
Mamalaki, E., Kvetnan̆ský, R., Brady, L., Gold, P., & Herkenham, M. (1992) · Journal of neuroendocrinology · doi:10.1111/j.1365-2826.1992.tb00220.x · Cited by 131 · see citing works
From Malthus to motive: How the HPA axis engineers the phenotype, yoking needs to wants
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Adrenergic receptors mediate changes in c-fos mRNA levels in brain
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Role of the basolateral amygdala in memory consolidation
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“Abundant evidence indicates that the discharge rate of locus coeruleus neurons increases during stress (Abercrombie and Jacobs, 1987a,b).”
BackgroundAntagonism of endogenous CRH systems attenuates stress-induced freezing behavior in rats.
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Maternal and child posttraumatic stress disorder in cases of child maltreatment.
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Human amygdala reactivity is diminished by the β-noradrenergic antagonist propranolol
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“In the DR, neither TPH2 nor galanin mRNA transcript levels were significantly affected by the swim/ injection stress, consistent with the view that the LC NA system is more sensitive to acute stress than the DR (Abercrombie and Jacobs, 1987; Wilkinson and Jacobs, 1988).”
BackgroundVahabzadeh, A., & Fillenz, M. (1994) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.1994.tb00619.x · Cited by 117 · see citing works
Effect of tyrosine on cognitive function and blood pressure under stress.
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Involvement of melanocortin-4 receptor in anxiety and depression
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“Noradrenergic projections from the locus coeruleus (LC), which show an increased electrical activity during stress, provide a main innervation to the frontal cortex [1,31].”
BackgroundActivity of cat locus coeruleus noradrenergic neurons during the defense reaction.
Levine, E., Litto, W., & Jacobs, B. (1990) · Brain Research · doi:10.1016/0006-8993(90)90773-5 · Cited by 113 · see citing works
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“Because of technical limitations, fewer studies have recorded LC discharge during stress and most of these have examined the effect of physiological stressors on tonic (i.e., spontaneous), but not phasic LC activity (Abercrombie and Jacobs, 1987; Curtis et al., 1993; Morilak et al., 1987a, b).”
BackgroundNoradrenergic enhancement of amygdala responses to fear
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“Neurons in the LC are activated by stressful stimuli (Abercrombie and Jacobs, 1987) and mediate the stress-induced enhancement of NE neurotransmission in the BLA (Buffalari and Grace, 2007).”
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Rodr�guez, J. J., & Pickel, V. M. (1999) · Synapse · doi:10.1002/(sici)1098-2396(19990915)33:4 · Cited by 19 · see citing works
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Ni, Y., Gold, S., Iredale, P., Terwilliger, R. Z., Duman, R., & Nestler, E. J. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-10-03674.1999 · Cited by 105 · see citing works
“Acute or chronic stress increases the spontaneous firing rate of LC neurons (Abercrombie and Jacobs, 1987; Simson and Weiss, 1988; Pavcovich and Ramirez, 1991) and the expression of tyrosine hydroxylase, the rate-limiting enzyme for norepinephrine biosynthesis (Thoenen, 1970; Zigmond et al., 1974;…”
Background
- Authors
- Abercrombie, E., & Jacobs, B.
- Affiliations
- University of Pittsburgh (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1987-09-01
- Volume
- 7
- Issue
- 9
- Pages
- 2837-2843
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6569145
- OpenAlex
- W1924384005
- Cited by
- 377
- References
- 38
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 2 · 2022: 5 · 2021: 7 · 2020: 8 · 2019: 5 · 2018: 7 · 2017: 5 · 2016: 11 · 2015: 5 · 2014: 12 · 2013: 12 · 2012: 10
- FWCI
- 6.22
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Rutgers University Community Repository (Rutgers University) (submittedVersion)
- Funders
- National Institute of Mental Health (MH23433, MH09256)
- Air Force Office of Scientific Research
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
- Keywords
- locus coeruleus, noradrenergic neurons, stress response, single-unit activity, plasma norepinephrine, heart rate, restraint stress, white noise, behavioral activation, cats
- MeSH terms
- Animals, Behavior, Animal, Cats, Female, Heart Rate, Locus Coeruleus, Male, Neurons, Norepinephrine, Stress, Physiological
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