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LC-NE system

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LC-NE = locus coeruleus neroepiniphrine

The locus coeruleus is responsible for mediating many of the sympathetic effects during stress. The locus coeruleus is activated by stress, and will respond by increasing norepinephrine secretion, which in turn will alter cognitive function (through the prefrontal cortex), increase motivation (through nucleus accumbens), activate the hypothalamic-pituitary-adrenal axis, and increase the sympathetic discharge/inhibit parasympathetic tone (through the brainstem). Specific to the activation of the hypothalamo-pituitary adrenal axis, norepinephrine will stimulate the secretion of corticotropin-releasing factor] from the hypothalamus, which induces adrenocorticotropic hormone release from the anterior pituitary and subsequent cortisol synthesis in the adrenal glands. Norepinephrine released from locus coeruleus will feedback to inhibit its production, and corticotropin-releasing hormone will feedback to inhibit its production, while positively feeding to the locus coeruleus to increase norepinephrine production.[1]

The LC's role in cognitive function in relation to stress is complex and multi-modal. Norepinephrine released from the LC can act on α2 receptors to increase working memory, or an excess of NE may decrease working memory by binding to the lower-affinity α1 receptors.[2] . LC-NE and ACC may modulate aroused attention in a novel environment and new social environment, and stay aroused by feedback from the ACC. It is also seems that the ACC is a key compnent in passing the massage of arousal from the LC-NE system[3].

LC-ACC regulation.jpg

Existing evidence suggests that the locus coeruleus–norepinephrine (LC-NE) system serves to modulate neural gain throughout the brain[4][5][6][7][8][9]


LC and the corrolation with wakefulness

There is a strong corrolation between CL firing and wakefulness levels. LC neural activity is highest during wakefulness, progressively lower during non-rapid eye movement (REM) sleep, and nearly absent during REM sleep[10]. A more causal finidngs were astablished when inhibiton and stimulation of LC by drugs were mediated to the LC, and that changed the levels of wakefulness[11][12]. but both the drugs and current may spread beyond the LC to other structures in the dorsolateral pons that may also play important roles in arousal and wake–sleep control, such as the parabrachial nucleus and the preceruleus region[13]. Chemical or genetic lesions limited to the LC produce only small effects on the amount or timing of wakefulness. The role of the LC in arousal remains unclear. (source)

LC and Novel Environmental Stimuli

LC neurons do respond vigorously to novel environmental stimuli[14]. A more causal link was found when fharmacological inhibition of LC transmission impaired exploratory behavior[15].

LC innervation provides the cerebral cortex including the ACC with noradrenaline during times of elevated arousal and focused attention[16].

It seems that LC-NE relese Norepinephrine to ACC, which then elvate wakeness. The ACC send signals to the LC, to maintain wakeness while new stimules are precived[17]

References

  1. ↑ Benarroch EE. The locus ceruleus norepinephrine system: functional organization and potential clinical significance. Neurology. 2009 Nov 17;73(20):1699-704.
  2. ↑ Ramos BP, Arnsten AF. Adrenergic pharmacology and cognition: focus on the prefrontal cortex. Pharmacol Ther 2007; 113: 523-536.
  3. ↑ Heinrich S Gompf, Christine Mathai, Patrick M Fuller, David A Wood, Nigel P Pedersen, Clifford B Saper, and Jun Lu, 2011, Locus coeruleus (LC) and anterior cingulate cortex sustain wakefulness in a novel environment, Neurosci. Oct 27, 2010; 30(43): 14543–14551.
  4. ↑ Aston-Jones, G. & Cohen, J.D. An integrative theory of locus coeruleus–norepinephrine function: adaptive gain and optimal performance. Annu. Rev. Neurosci. 28, 403–450 (2005).
  5. ↑ Gilzenrat, M.S., Nieuwenhuis, S., Jepma, M. & Cohen, J.D. Pupil diameter tracks changes in control state predicted by the adaptive gain theory of locus coeruleus function. Cogn. Affect. Behav. Neurosci. 10, 252–269 (2010).
  6. ↑ Jepma, M. & Nieuwenhuis, S. Pupil diameter predicts changes in the exploration-exploitation trade-off: evidence for the adaptive gain theory. J. Cogn. Neurosci. 23, 1587–1596 (2011).
  7. ↑ Waterhouse, B.D., Moises, H.C. & Woodward, D.J. Noradrenergic modulation of somatosensory cortical neuronal responses to lontophoretically applied putative neurotransmitters. Exp. Neurol. 69, 30–49 (1980).
  8. ↑ Waterhouse, B.D., Moises, H.C., Yeh, H.H., Geller, H.M. & Woodward, D.J. Comparison of norepinephrine- and benzodiazepine-induced augmentation of Purkinje cell responses to gamma-aminobutyric acid (GABA). J. Pharmacol. Exp. Ther. 228, 257–267 (1984).
  9. ↑ Waterhouse, B.D. & Woodward, D.J. Interaction of norepinephrine with cerebrocortical activity evoked by stimulation of somatosensory afferent pathways in the rat. Exp. Neurol. 67, 11–34 (1980).
  10. ↑ Aston-Jones G, Bloom FE (1981) Activity of norepinephrine-containing locus coeruleus neurons in behaving rats anticipates fluctuations in the sleep-waking cycle. J Neurosci 1:876–886.
  11. ↑ Berridge CW, Foote SL (1991) Effects of locus coeruleus activation on electroencephalographic activity in neocortex and hippocampus. J Neurosci 11:3135–3145.
  12. ↑ Berridge CW, Waterhouse BD (2003) The locus coeruleus-noradrenergic system: modulation of behavioral state and state-dependent cognitive processes. Brain Res Brain Res Rev 42:33–84.
  13. ↑ Lu J, Jhou TC, Saper CB (2006) Identification of wake-active dopaminergic neurons in the ventral periaqueductal gray matter. J Neurosci 26:193–202.
  14. ↑ Vankov A, Hervé-Minvielle A, Sara SJ (1995) Response to novelty and its rapid habituation in locus coeruleus neurons of the freely exploring rat. Eur J Neurosci 7:1180–1187.
  15. ↑ Sara SJ, Dyon-Laurent C, Hervé A (1995) Novelty seeking behavior in the rat is dependent upon the integrity of the noradrenergic system. Brain Res Cogn Brain Res 2:181–187
  16. ↑ Aston-Jones G, Cohen JD (2005) An integrative theory of locus coeruleus-norepinephrine function: adaptive gain and optimal performance. Annu Rev Neurosci 28:403–450.
  17. ↑ Heinrich S. Gompf, Christine Mathai, Patrick M. Fuller, David A. Wood, Nigel P. Pedersen, Clifford B. Saper, and Jun Lu (2010) Locus Ceruleus and Anterior Cingulate Cortex Sustain Wakefulness in a Novel Environment, The Journal of Neuroscience, 27 October 2010, 30(43): 14543-14551
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