Abstract
Norepinephrine (NE) is a neuromodulator that in multiple ways regulates the activity of neuronal and non-neuronal cells. NE participates in the rapid modulation of cortical circuits and cellular energy metabolism, and on a slower time scale in neuroplasticity and inflammation. Of the multiple sources of NE in the brain, the locus coeruleus (LC) plays a major role in noradrenergic signaling. Processes from the LC primarily release NE over widespread brain regions via non-junctional varicosities. We here review the actions of NE in astrocytes, microglial cells, and neurons based on the idea that the overarching effect of signaling from the LC is to maximize brain power, which is accomplished via an orchestrated cellular response involving most, if not all cell types in CNS.
This is a preview of subscription content, log in to check access.
References
-
1.
Descarries L, Saucier G (1972) Disappearance of the locus coeruleus in the rat after intraventricular 6-hydroxdopamine. Brain Res 37:310–316
-
2.
Seguela P, Watkins KC, Geffard M, Descarries L (1990) Noradrenaline axon terminals in adult rat neocortex: an immunocytochemical analysis in serial thin sections. Neuroscience 35:249–264
-
3.
Agnati LF, Bjelke B, Fuxe K (1995) Volume versus wiring transmission in the brain: a new theoretical frame for neuropsychopharmacology. Med Res Rev 15:33–45
-
4.
Audet MA, Doucet G, Oleskevich S, Descarries L (1988) Quantified regional and laminar distribution of the noradrenaline innervation in the anterior half of the adult rat cerebral cortex. J Comp Neurol 274:307–318
-
5.
Levitt P, Moore RY (1978) Noradrenaline neuron innervation of the neocortex in the rat. Brain Res 139:219–231
-
6.
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
-
7.
Herve-Minvielle A, Sara SJ (1995) Rapid habituation of auditory responses of locus coeruleus cells in anaesthetized and awake rats. NeuroReport 6:1363–1368
-
8.
Hirata H, Aston-Jones G (1994) A novel long-latency response of locus coeruleus neurons to noxious stimuli: mediation by peripheral C-fibers. J Neurophysiol 71:1752–1761
-
9.
Vankov A, Herve-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
-
10.
Aoki C, Pickel VM (1992) Ultrastructural relations between beta-adrenergic receptors and catecholaminergic neurons. Brain Res Bull 29:257–263
-
11.
Cohen Z, Molinatti G, Hamel E (1997) Astroglial and vascular interactions of noradrenaline terminals in the rat cerebral cortex. J Cereb Blood Flow Metab 17:894–904
-
12.
Paspalas CD, Papadopoulos GC (1996) Ultrastructural relationships between noradrenergic nerve fibers and non-neuronal elements in the rat cerebral cortex. Glia 17:133–146
-
13.
Mori K, Ozaki E, Zhang B, Yang L, Yokoyama A, Takeda I, Maeda N, Sakanaka M, Tanaka J (2002) Effects of norepinephrine on rat cultured microglial cells that express alpha1, alpha2, beta1 and beta2 adrenergic receptors. Neuropharmacology 43:1026–1034
-
14.
Pocock JM, Kettenmann H (2007) Neurotransmitter receptors on microglia. Trends Neurosci 30:527–535
-
15.
Alexander GM, Grothusen JR, Gordon SW, Schwartzman RJ (1997) Intracerebral microdialysis study of glutamate reuptake in awake, behaving rats. Brain Res 766:1–10
-
16.
Hertz L, Lovatt D, Goldman SA, Nedergaard M (2010) Adrenoceptors in brain: cellular gene expression and effects on astrocytic metabolism and [Ca(2+)]i. Neurochem Int 57:411–420
-
17.
Anderson CM, Swanson RA (2000) Astrocyte glutamate transport: review of properties, regulation, and physiological functions. Glia 32:1–14
-
18.
Hertz L, Peng L, Dienel GA (2007) Energy metabolism in astrocytes: high rate of oxidative metabolism and spatiotemporal dependence on glycolysis/glycogenolysis. J Cereb Blood Flow Metab 27:219–249
-
19.
Shao Y, Sutin J (1992) Expression of adrenergic receptors in individual astrocytes and motor neurons isolated from the adult rat brain. Glia 6:108–117
-
20.
Thorlin T, Eriksson PS, Ronnback L, Hansson E (1998) Receptor-activated Ca2+ increases in vibrodissociated cortical astrocytes: a nonenzymatic method for acute isolation of astrocytes. J Neurosci Res 54:390–401
-
21.
Bekar LK, He W, Nedergaard M (2008) Locus coeruleus alpha-adrenergic-mediated activation of cortical astrocytes in vivo. Cereb Cortex 18:2789–2795
-
22.
Berridge MJ, Irvine RF (1984) Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature 312:315–321
-
23.
Yoshida Y, Imai S (1997) Structure and function of inositol 1,4,5-trisphosphate receptor. Jpn J Pharmacol 74:125–137
-
24.
Hertz L, Schousboe A, Boechler N, Mukerji S, Fedoroff S (1978) Kinetic characteristics of the glutamate uptake into normal astrocytes in cultures. Neurochem Res 3:1–14
-
25.
Aoki C, Venkatesan C, Kurose H (1998) Noradrenergic modulation of the prefrontal cortex as revealed by electron microscopic immunocytochemistry. Adv Pharmacol 42:777–780
-
26.
Catus SL, Gibbs ME, Sato M, Summers RJ, Hutchinson DS (2011) Role of beta-adrenoceptors in glucose uptake in astrocytes using beta-adrenoceptor knockout mice. Br J Pharmacol 162:1700–1715
-
27.
Glass MJ, Huang J, Aicher SA, Milner TA, Pickel VM (2001) Subcellular localization of alpha-2A-adrenergic receptors in the rat medial nucleus tractus solitarius: regional targeting and relationship with catecholamine neurons. J Comp Neurol 433:193–207
-
28.
Cahoy JD, Emery B, Kaushal A, Foo LC, Zamanian JL, Christopherson KS, Xing Y, Lubischer JL, Krieg PA, Krupenko SA, Thompson WJ, Barres BA (2008) A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function. J Neurosci 28:264–278
-
29.
Hansson E (1988) Astroglia from defined brain regions as studied with primary cultures. Prog Neurobiol 30:369–397
-
30.
Werry TD, Wilkinson GF, Willars GB (2003) Mechanisms of cross-talk between G-protein-coupled receptors resulting in enhanced release of intracellular Ca2+. Biochem J 374:281–296
-
31.
Shulman RG, Hyder F, Rothman DL (2001) Cerebral energetics and the glycogen shunt: neurochemical basis of functional imaging. Proc Nat Acad Sci USA 98:6417–6422
-
32.
Chen Y, Hertz L (1999) Noradrenaline effects on pyruvate decarboxylation: correlation with calcium signaling. J Neurosci Res 58:599–606
-
33.
Chen Y, Zhao Z, Code WE, Hertz L (2000) A correlation between dexmedetomidine-induced biphasic increases in free cytosolic calcium concentration and energy metabolism in astrocytes. Anesth Analg 91:353–357
-
34.
Quach TT, Duchemin AM, Rose C, Schwartz JC (1988) [3H]Glycogenolysis in brain slices mediated by beta-adrenoceptors: comparison of physiological response and [3H]dihydroalprenolol binding parameters. Neuropharmacology 27:629–635
-
35.
Denton RM, Randle PJ, Bridges BJ, Cooper RH, Kerbey AL, Pask HT, Severson DL, Stansbie D, Whitehouse S (1975) Regulation of mammalian pyruvate dehydrogenase. Mol Cell Biochem 9:27–53
-
36.
Pesce L, Comellas A, Sznajder JI (2003) Beta-adrenergic agonists regulate Na-K-ATPase via p70S6k. Am J Physiol Lung Cell Mol Physiol 285:L802–L807
-
37.
Hajek I, Subbarao KV, Hertz L (1996) Acute and chronic effects of potassium and noradrenaline on Na+, K+-ATPase activity in cultured mouse neurons and astrocytes. Neurochem Int 28:335–342
-
38.
Tremblay ME, Stevens B, Sierra A, Wake H, Bessis A, Nimmerjahn A (2011) The role of microglia in the healthy brain. J Neurosci 31:16064–16069
-
39.
Kettenmann H, Hanisch UK, Noda M, Verkhratsky A (2011) Physiology of microglia. Physiol Rev 91:461–553
-
40.
Heneka MT, Nadrigny F, Regen T, Martinez-Hernandez A, Dumitrescu-Ozimek L, Terwel D, Jardanhazi-Kurutz D, Walter J, Kirchhoff F, Hanisch UK, Kummer MP (2010) Locus ceruleus controls Alzheimer’s disease pathology by modulating microglial functions through norepinephrine. Proc Nat Acad Sci USA 107:6058–6063
-
41.
Frohman EM, Vayuvegula B, Gupta S, van den Noort S (1988) Norepinephrine inhibits gamma-interferon-induced major histocompatibility class II (Ia) antigen expression on cultured astrocytes via beta-2-adrenergic signal transduction mechanisms. Proc Nat Acad Sci USA 85:1292–1296
-
42.
Hetier E, Ayala J, Bousseau A, Prochiantz A (1991) Modulation of interleukin-1 and tumor necrosis factor expression by beta-adrenergic agonists in mouse ameboid microglial cells. Exp Brain Res 86:407–413
-
43.
Steininger TS, Stutz H, Kerschbaum HH (2011) Beta-adrenergic stimulation suppresses phagocytosis via Epac activation in murine microglial cells. Brain Res 1407:1–12
-
44.
Tanaka KF, Kashima H, Suzuki H, Ono K, Sawada M (2002) Existence of functional beta1- and beta2-adrenergic receptors on microglia. J Neurosci Res 70:232–237
-
45.
Davalos D, Grutzendler J, Yang G, Kim JV, Zuo Y, Jung S, Littman DR, Dustin ML, Gan WB (2005) ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci 8:752–758
-
46.
Nimmerjahn A, Kirchhoff F, Helmchen F (2005) Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308:1314–1318
-
47.
Stence N, Waite M, Dailey ME (2001) Dynamics of microglial activation: a confocal time-lapse analysis in hippocampal slices. Glia 33:256–266
-
48.
Kong Y, Ruan L, Qian L, Liu X, Le Y (2010) Norepinephrine promotes microglia to uptake and degrade amyloid beta peptide through upregulation of mouse formyl peptide receptor 2 and induction of insulin-degrading enzyme. J Neurosci 30:11848–11857
-
49.
Cammermeyer J (1965) Juxtavascular karyokinesis and microglia cell proliferation during retrograde reaction in the mouse facial nucleus. Ergeb Anat Entwicklungsgesch 38:1–22
-
50.
Graeber MB, Tetzlaff W, Streit WJ, Kreutzberg GW (1988) Microglial cells but not astrocytes undergo mitosis following rat facial nerve axotomy. Neurosci Lett 85:317–321
-
51.
Fujita H, Tanaka J, Maeda N, Sakanaka M (1998) Adrenergic agonists suppress the proliferation of microglia through beta 2-adrenergic receptor. Neurosci Lett 242:37–40
-
52.
Farber K, Kettenmann H (2006) Purinergic signaling and microglia. Pflugers Arch 452:615–621
-
53.
Marien MR, Colpaert FC, Rosenquist AC (2004) Noradrenergic mechanisms in neurodegenerative diseases: a theory. Brain Res Brain Res Rev 45:38–78
-
54.
Rock RB, Gekker G, Hu S, Sheng WS, Cheeran M, Lokensgard JR, Peterson PK (2004) Role of microglia in central nervous system infections. Clin Microbiol Rev 17:942–964, table of contents
-
55.
Aloisi F (1999) The role of microglia and astrocytes in CNS immune surveillance and immunopathology. Adv Exp Med Biol 468:123–133
-
56.
Banati RB, Gehrmann J, Schubert P, Kreutzberg GW (1993) Cytotoxicity of microglia. Glia 7:111–118
-
57.
Heneka MT, Galea E, Gavriluyk V, Dumitrescu-Ozimek L, Daeschner J, O’Banion MK, Weinberg G, Klockgether T, Feinstein DL (2002) Noradrenergic depletion potentiates beta-amyloid-induced cortical inflammation: implications for Alzheimer’s disease. J Neurosci 22:2434–2442
-
58.
Michelucci A, Heurtaux T, Grandbarbe L, Morga E, Heuschling P (2009) Characterization of the microglial phenotype under specific pro-inflammatory and anti-inflammatory conditions: effects of oligomeric and fibrillar amyloid-beta. J Neuroimmunol 210:3–12
-
59.
Willis SA, Nisen PD (1995) Inhibition of lipopolysaccharide-induced IL-1 beta transcription by cyclic adenosine monophosphate in human astrocytic cells. J Immunol 154:1399–1406
-
60.
Feinstein DL, Galea E, Reis DJ (1993) Norepinephrine suppresses inducible nitric oxide synthase activity in rat astroglial cultures. J Neurochem 60:1945–1948
-
61.
Feinstein DL, Heneka MT, Gavrilyuk V, Dello Russo C, Weinberg G, Galea E (2002) Noradrenergic regulation of inflammatory gene expression in brain. Neurochem Int 41:357–365
-
62.
Saura J (2007) Microglial cells in astroglial cultures: a cautionary note. J Neuroinflammation 4:26
-
63.
Feinstein DL (1998) Suppression of astroglial nitric oxide synthase expression by norepinephrine results from decreased NOS-2 promoter activity. J Neurochem 70:1484–1496
-
64.
Ballestas ME, Benveniste EN (1997) Elevation of cyclic AMP levels in astrocytes antagonizes cytokine-induced adhesion molecule expression. J Neurochem 69:1438–1448
-
65.
Etienne-Manneville S, Chaverot N, Strosberg AD, Couraud PO (1999) ICAM-1-coupled signaling pathways in astrocytes converge to cyclic AMP response element-binding protein phosphorylation and TNF-alpha secretion. J Immunol 163:668–674
-
66.
Benveniste EN, Huneycutt BS, Shrikant P, Ballestas ME (1995) Second messenger systems in the regulation of cytokines and adhesion molecules in the central nervous system. Brain Behav Immun 9:304–314
-
67.
Griffin WS, Sheng JG, Royston MC, Gentleman SM, McKenzie JE, Graham DI, Roberts GW, Mrak RE (1998) Glial-neuronal interactions in Alzheimer’s disease: the potential role of a ‘cytokine cycle’ in disease progression. Brain Pathol 8:65–72
-
68.
Campbell A (2004) Inflammation, neurodegenerative diseases, and environmental exposures. Ann N Y Acad Sci 1035:117–132
-
69.
Opp MR (2005) Cytokines and sleep. Sleep Med Rev 9:355–364
-
70.
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
-
71.
Zafra F, Lindholm D, Castren E, Hartikka J, Thoenen H (1992) Regulation of brain-derived neurotrophic factor and nerve growth factor mRNA in primary cultures of hippocampal neurons and astrocytes. J Neurosci 12:4793–4799
-
72.
Binder DK, Scharfman HE (2004) Brain-derived neurotrophic factor. Growth Factors 22:123–131
-
73.
Juric DM, Loncar D, Carman-Krzan M (2008) Noradrenergic stimulation of BDNF synthesis in astrocytes: mediation via alpha1- and beta1/beta2-adrenergic receptors. Neurochem Int 52:297–306
-
74.
Juric DM, Miklic S, Carman-Krzan M (2006) Monoaminergic neuronal activity up-regulates BDNF synthesis in cultured neonatal rat astrocytes. Brain Res 1108:54–62
-
75.
Coull JA, Beggs S, Boudreau D, Boivin D, Tsuda M, Inoue K, Gravel C, Salter MW, De Koninck Y (2005) BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature 438:1017–1021
-
76.
Turrigiano GG, Leslie KR, Desai NS, Rutherford LC, Nelson SB (1998) Activity-dependent scaling of quantal amplitude in neocortical neurons. Nature 391:892–896
-
77.
Davis GW, Bezprozvanny I (2001) Maintaining the stability of neural function: a homeostatic hypothesis. Annu Rev Physiol 63:847–869
-
78.
Turrigiano GG (2008) The self-tuning neuron: synaptic scaling of excitatory synapses. Cell 135:422–435
-
79.
Beattie EC, Stellwagen D, Morishita W, Bresnahan JC, Ha BK, Von Zastrow M, Beattie MS, Malenka RC (2002) Control of synaptic strength by glial TNFalpha. Science 295:2282–2285
-
80.
Stellwagen D, Beattie EC, Seo JY, Malenka RC (2005) Differential regulation of AMPA receptor and GABA receptor trafficking by tumor necrosis factor-alpha. J Neurosci 25:3219–3228
-
81.
Stellwagen D, Malenka RC (2006) Synaptic scaling mediated by glial TNF-alpha. Nature 440:1054–1059
-
82.
Rutherford LC, Nelson SB, Turrigiano GG (1998) BDNF has opposite effects on the quantal amplitude of pyramidal neuron and interneuron excitatory synapses. Neuron 21:521–530
-
83.
Leslie KR, Nelson SB, Turrigiano GG (2001) Postsynaptic depolarization scales quantal amplitude in cortical pyramidal neurons. J Neurosci 21:RC170
-
84.
Papay R, Gaivin R, Jha A, McCune DF, McGrath JC, Rodrigo MC, Simpson PC, Doze VA, Perez DM (2006) Localization of the mouse alpha1A-adrenergic receptor (AR) in the brain: alpha1AAR is expressed in neurons, GABAergic interneurons, and NG2 oligodendrocyte progenitors. J Comp Neurol 497:209–222
-
85.
Venkatesan C, Song XZ, Go CG, Kurose H, Aoki C (1996) Cellular and subcellular distribution of alpha 2A-adrenergic receptors in the visual cortex of neonatal and adult rats. J Comp Neurol 365:79–95
-
86.
McCormick DA (1992) Neurotransmitter actions in the thalamus and cerebral cortex. J Clin Neurophysiol 9:212–223
-
87.
Haas HL, Rose GM (1987) Noradrenaline blocks potassium conductance in rat dentate granule cells in vitro. Neurosci Lett 78:171–174
-
88.
Sah P, French CR, Gage PW (1985) Effects of noradrenaline on some potassium currents in CA1 neurones in rat hippocampal slices. Neurosci Lett 60:295–300
-
89.
Sah P, Isaacson JS (1995) Channels underlying the slow after hyperpolarization in hippocampal pyramidal neurons: neurotransmitters modulate the open probability. Neuron 15:435–441
-
90.
Pedarzani P, Storm JF (1993) PKA mediates the effects of monoamine transmitters on the K+ current underlying the slow spike frequency adaptation in hippocampal neurons. Neuron 11:1023–1035
-
91.
Hu H, Real E, Takamiya K, Kang MG, Ledoux J, Huganir RL, Malinow R (2007) Emotion enhances learning via norepinephrine regulation of AMPA-receptor trafficking. Cell 131:160–173
-
92.
Barth AM, Vizi ES, Zelles T, Lendvai B (2008) Alpha2-adrenergic receptors modify dendritic spike generation via HCN channels in the prefrontal cortex. J Neurophysiol 99:394–401
-
93.
Wang M, Ramos BP, Paspalas CD, Shu Y, Simen A, Duque A, Vijayraghavan S, Brennan A, Dudley A, Nou E, Mazer JA, McCormick DA, Arnsten AF (2007) Alpha2A-adrenoceptors strengthen working memory networks by inhibiting cAMP-HCN channel signaling in prefrontal cortex. Cell 129:397–410
-
94.
Agler HL, Evans J, Tay LH, Anderson MJ, Colecraft HM, Yue DT (2005) G protein-gated inhibitory module of N-type (Ca(v)2.2) Ca2+ channels. Neuron 46:891–904
-
95.
Timmons SD, Geisert E, Stewart AE, Lorenzon NM, Foehring RC (2004) alpha2-Adrenergic receptor-mediated modulation of calcium current in neocortical pyramidal neurons. Brain Res 1014:184–196
-
96.
Boehm S (1999) Presynaptic alpha2-adrenoceptors control excitatory, but not inhibitory, transmission at rat hippocampal synapses. J Physiol 519(Pt 2):439–449
-
97.
Barrett CF, Rittenhouse AR (2000) Modulation of N-type calcium channel activity by G-proteins and protein kinase C. J Gen Physiol 115:277–286
-
98.
Strock J, Diverse-Pierluissi MA (2004) Ca2+ channels as integrators of G protein-mediated signaling in neurons. Mol Pharmacol 66:1071–1076
-
99.
Sessler FM, Liu W, Kirifides ML, Mouradian RD, Lin RC, Waterhouse BD (1995) Noradrenergic enhancement of GABA-induced input resistance changes in layer V regular spiking pyramidal neurons of rat somatosensory cortex. Brain Res 675:171–182
-
100.
Giorgi FS, Pizzanelli C, Biagioni F, Murri L, Fornai F (2004) The role of norepinephrine in epilepsy: from the bench to the bedside. Neurosci Biobehav Rev 28:507–524
-
101.
Libet B, Gleason CA, Wright EW Jr, Feinstein B (1977) Suppression of an eplieptiform type of electrocortical activity in the rat by stimulation in the vicinity of locus coeruleus. Epilepsia 18:451–462
-
102.
Neuman RS (1986) Suppression of penicillin-induced focal epileptiform activity by locus ceruleus stimulation: mediation by an alpha 1-adrenoceptor. Epilepsia 27:359–366
-
103.
Bergles DE, Doze VA, Madison DV, Smith SJ (1996) Excitatory actions of norepinephrine on multiple classes of hippocampal CA1 interneurons. J Neurosci 16:572–585
-
104.
Hillman KL, Lei S, Doze VA, Porter JE (2009) Alpha-1A adrenergic receptor activation increases inhibitory tone in CA1 hippocampus. Epilepsy Res 84:97–109
-
105.
Kawaguchi Y, Shindou T (1998) Noradrenergic excitation and inhibition of GABAergic cell types in rat frontal cortex. J Neurosci 18:6963–6976
-
106.
Lei S, Deng PY, Porter JE, Shin HS (2007) Adrenergic facilitation of GABAergic transmission in rat entorhinal cortex. J Neurophysiol 98:2868–2877
-
107.
Salgado H, Garcia-Oscos F, Patel A, Martinolich L, Nichols JA, Dinh L, Roychowdhury S, Tseng KY, Atzori M (2011) Layer-specific noradrenergic modulation of inhibition in cortical layer II/III. Cereb Cortex 21:212–221
-
108.
Devilbiss DM, Waterhouse BD (2000) Norepinephrine exhibits two distinct profiles of action on sensory cortical neuron responses to excitatory synaptic stimuli. Synapse 37:273–282
-
109.
Marek GJ, Aghajanian GK (1999) 5-HT2A receptor or alpha1-adrenoceptor activation induces excitatory postsynaptic currents in layer V pyramidal cells of the medial prefrontal cortex. Eur J Pharmacol 367:197–206
-
110.
Waterhouse BD, Mouradian R, Sessler FM, Lin RC (2000) Differential modulatory effects of norepinephrine on synaptically driven responses of layer V barrel field cortical neurons. Brain Res 868:39–47
-
111.
Kobayashi M (2007) Differential regulation of synaptic transmission by adrenergic agonists via protein kinase A and protein kinase C in layer V pyramidal neurons of rat cerebral cortex. Neuroscience 146:1772–1784
-
112.
Kobayashi M, Kojima M, Koyanagi Y, Adachi K, Imamura K, Koshikawa N (2009) Presynaptic and postsynaptic modulation of glutamatergic synaptic transmission by activation of alpha(1)- and beta-adrenoceptors in layer V pyramidal neurons of rat cerebral cortex. Synapse 63:269–281
-
113.
Kobayashi M, Sasabe T, Shiohama Y, Koshikawa N (2008) Activation of alpha1-adrenoceptors increases firing frequency through protein kinase C in pyramidal neurons of rat visual cortex. Neurosci Lett 430:175–180
-
114.
Hirata A, Aguilar J, Castro-Alamancos MA (2006) Noradrenergic activation amplifies bottom-up and top-down signal-to-noise ratios in sensory thalamus. J Neurosci 26:4426–4436
-
115.
Nieuwenhuis S, Aston-Jones G, Cohen JD (2005) Decision making, the P3, and the locus coeruleus-norepinephrine system. Psychol Bull 131:510–532
-
116.
Sara SJ, Segal M (1991) Plasticity of sensory responses of locus coeruleus neurons in the behaving rat: implications for cognition. Prog Brain Res 88:571–585
-
117.
Chen FJ, Sara SJ (2007) Locus coeruleus activation by foot shock or electrical stimulation inhibits amygdala neurons. Neuroscience 144:472–481
-
118.
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
-
119.
Castro-Alamancos MA (2002) Role of thalamocortical sensory suppression during arousal: focusing sensory inputs in neocortex. J Neurosci 22:9651–9655
-
120.
Foote SL, Freedman R, Oliver AP (1975) Effects of putative neurotransmitters on neuronal activity in monkey auditory cortex. Brain Res 86:229–242
-
121.
Waterhouse BD, Woodward DJ (1980) Interaction of norepinephrine with cerebrocortical activity evoked by stimulation of somatosensory afferent pathways in the rat. Exp Neurol 67:11–34
-
122.
Castro-Alamancos MA, Calcagnotto ME (2001) High-pass filtering of corticothalamic activity by neuromodulators released in the thalamus during arousal: in vitro and in vivo. J Neurophysiol 85:1489–1497
-
123.
Ptak R (2011) The frontoparietal attention network of the human brain: action, saliency, and a priority map of the environment. Neuroscientist. doi:10.1177/1073858411409051
-
124.
Aghajanian GK, Wang YY (1987) Common alpha 2- and opiate effector mechanisms in the locus coeruleus: intracellular studies in brain slices. Neuropharmacology 26:793–799
-
125.
Ivanov A, Aston-Jones G (1995) Extranuclear dendrites of locus coeruleus neurons: activation by glutamate and modulation of activity by alpha adrenoceptors. J Neurophysiol 74:2427–2436
-
126.
Mair RD, Zhang Y, Bailey KR, Toupin MM, Mair RG (2005) Effects of clonidine in the locus coeruleus on prefrontal- and hippocampal-dependent measures of attention and memory in the rat. Psychopharmacology 181:280–288
-
127.
Coull JT, Buchel C, Friston KJ, Frith CD (1999) Noradrenergically mediated plasticity in a human attentional neuronal network. NeuroImage 10:705–715
-
128.
Goldman-Rakic PS (1995) Cellular basis of working memory. Neuron 14:477–485
-
129.
Wang M, Gamo NJ, Yang Y, Jin LE, Wang XJ, Laubach M, Mazer JA, Lee D, Arnsten AF (2011) Neuronal basis of age-related working memory decline. Nature 476:210–213
-
130.
Li BM, Mei ZT (1994) Delayed-response deficit induced by local injection of the alpha 2-adrenergic antagonist yohimbine into the dorsolateral prefrontal cortex in young adult monkeys. Behav Neural Biol 62:134–139
-
131.
Ramos BP, Colgan L, Nou E, Ovadia S, Wilson SR, Arnsten AF (2005) The beta-1 adrenergic antagonist, betaxolol, improves working memory performance in rats and monkeys. Biol Psychiatry 58:894–900
-
132.
Birnbaum S, Gobeske KT, Auerbach J, Taylor JR, Arnsten AF (1999) A role for norepinephrine in stress-induced cognitive deficits: alpha-1-adrenoceptor mediation in the prefrontal cortex. Biol Psychiatry 46:1266–1274
-
133.
Hermans EJ, van Marle HJ, Ossewaarde L, Henckens MJ, Qin S, van Kesteren MT, Schoots VC, Cousijn H, Rijpkema M, Oostenveld R, Fernandez G (2011) Stress-related noradrenergic activity prompts large-scale neural network reconfiguration. Science 334:1151–1153
-
134.
Ramos BP, Colgan LA, Nou E, Arnsten AF (2008) Beta2 adrenergic agonist, clenbuterol, enhances working memory performance in aging animals. Neurobiol Aging 29:1060–1069
-
135.
Arnsten AF (2011) Catecholamine influences on dorsolateral prefrontal cortical networks. Biol Psychiatry 69:e89–e99
-
136.
Lapiz MD, Morilak DA (2006) Noradrenergic modulation of cognitive function in rat medial prefrontal cortex as measured by attentional set shifting capability. Neuroscience 137:1039–1049
-
137.
Treviño M, Frey S, Köhr G (2011) Alpha-1 adrenergic receptors gate rapid orientation-specific reduction in visual discrimination. Cereb Cortex. doi:10.1093/cercor/bhr333
-
138.
Bouret S, Sara SJ (2005) Network reset: a simplified overarching theory of locus coeruleus noradrenaline function. Trends Neurosci 28:574–582
-
139.
Gelinas JN, Nguyen PV (2005) Beta-adrenergic receptor activation facilitates induction of a protein synthesis-dependent late phase of long-term potentiation. J Neurosci 25:3294–3303
-
140.
O’Dell TJ, Connor SA, Gelinas JN, Nguyen PV (2010) Viagra for your synapses: enhancement of hippocampal long-term potentiation by activation of beta-adrenergic receptors. Cell Signal 22:728–736
-
141.
Straube T, Korz V, Balschun D, Frey JU (2003) Requirement of beta-adrenergic receptor activation and protein synthesis for LTP-reinforcement by novelty in rat dentate gyrus. J Physiol 552:953–960
-
142.
Kitchigina V, Vankov A, Harley C, Sara SJ (1997) Novelty-elicited, noradrenaline-dependent enhancement of excitability in the dentate gyrus. Eur J Neurosci 9:41–47
-
143.
Seidenbecher T, Reymann KG, Balschun D (1997) A post-tetanic time window for the reinforcement of long-term potentiation by appetitive and aversive stimuli. Proc Natl Acad Sci USA 94:1494–1499
-
144.
Harley CW (2007) Norepinephrine and the dentate gyrus. Prog Brain Res 163:299–318
-
145.
Sara SJ (2009) The locus coeruleus and noradrenergic modulation of cognition. Nat Rev Neurosci 10:211–223
-
146.
Kirkwood A, Rozas C, Kirkwood J, Perez F, Bear MF (1999) Modulation of long-term synaptic depression in visual cortex by acetylcholine and norepinephrine. J Neurosci 19:1599–1609
-
147.
Kemp A, Manahan-Vaughan D (2008) The hippocampal CA1 region and dentate gyrus differentiate between environmental and spatial feature encoding through long-term depression. Cereb Cortex 18:968–977
-
148.
Rosenzweig ES, Barnes CA, McNaughton BL (2002) Making room for new memories. Nat Neurosci 5:6–8
-
149.
Reymann KG, Frey JU (2007) The late maintenance of hippocampal LTP: requirements, phases, ‘synaptic tagging’, ‘late-associativity’ and implications. Neuropharmacology 52:24–40
-
150.
Bliss TV, Collingridge GL (1993) A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361:31–39
-
151.
Frey U, Krug M, Reymann KG, Matthies H (1988) Anisomycin, an inhibitor of protein synthesis, blocks late phases of LTP phenomena in the hippocampal CA1 region in vitro. Brain Res 452:57–65
-
152.
Frey U, Morris RG (1998) Weak before strong: dissociating synaptic tagging and plasticity-factor accounts of late-LTP. Neuropharmacology 37:545–552
-
153.
Sajikumar S, Frey JU (2004) Late-associativity, synaptic tagging, and the role of dopamine during LTP and LTD. Neurobiol Learn Mem 82:12–25
-
154.
Connor SA, Wang YT, Nguyen PV (2011) Activation of {beta}-adrenergic receptors facilitates heterosynaptic translation-dependent long-term potentiation. J Physiol 589:4321–4340
-
155.
McElligott ZA, Winder DG (2008) Alpha1-adrenergic receptor-induced heterosynaptic long-term depression in the bed nucleus of the stria terminalis is disrupted in mouse models of affective disorders. Neuropsychopharmacology 33:2313–2323
-
156.
Gibbs ME, Summers RJ (2002) Role of adrenoceptor subtypes in memory consolidation. Prog Neurobiol 67:345–391
-
157.
Gibbs ME, Hutchinson DS, Summers RJ (2010) Noradrenaline release in the locus coeruleus modulates memory formation and consolidation; roles for alpha- and beta-adrenergic receptors. Neuroscience 170:1209–1222
-
158.
Gibbs ME, Anderson DG, Hertz L (2006) Inhibition of glycogenolysis in astrocytes interrupts memory consolidation in young chickens. Glia 54:214–222
-
159.
Hutchinson DS, Summers RJ, Gibbs ME (2008) Energy metabolism and memory processing: role of glucose transport and glycogen in responses to adrenoceptor activation in the chicken. Brain Res Bull 76:224–234
-
160.
Hertz L, Gibbs ME (2009) What learning in day-old chickens can teach a neurochemist: focus on astrocyte metabolism. J Neurochem 109(Suppl 1):10–16
-
161.
Daisley JN, Rose SP (2002) Amino acid release from the intermediate medial hyperstriatum ventrale (IMHV) of day-old chicks following a one-trial passive avoidance task. Neurobiol Learn Mem 77:185–201
-
162.
Hertz L, O’Dowd BS, Ng KT, Gibbs ME (2003) Reciprocal changes in forebrain contents of glycogen and of glutamate/glutamine during early memory consolidation in the day-old chick. Brain Res 994:226–233
-
163.
Gibbs ME, Hutchinson D, Hertz L (2008) Astrocytic involvement in learning and memory consolidation. Neurosci Biobehav Rev 32:927–944
-
164.
Gibbs ME, Hutchinson DS, Summers RJ (2008) Role of beta-adrenoceptors in memory consolidation: beta3-adrenoceptors act on glucose uptake and beta2-adrenoceptors on glycogenolysis. Neuropsychopharmacology 33:2384–2397
-
165.
Pellerin L, Bouzier-Sore AK, Aubert A, Serres S, Merle M, Costalat R, Magistretti PJ (2007) Activity-dependent regulation of energy metabolism by astrocytes: an update. Glia 55:1251–1262
-
166.
Walz W (2000) Role of astrocytes in the clearance of excess extracellular potassium. Neurochem Int 36:291–300
-
167.
Suzuki A, Stern SA, Bozdagi O, Huntley GW, Walker RH, Magistretti PJ, Alberini CM (2011) Astrocyte-neuron lactate transport is required for long-term memory formation. Cell 144:810–823
-
168.
Gibbs ME, Bowser DN (2010) Astrocytic adrenoceptors and learning: alpha1-adrenoceptors. Neurochem Int 57:404–410
-
169.
Hutchinson DS, Catus SL, Merlin J, Summers RJ, Gibbs ME (2011) α2-Adrenoceptors activate noradrenaline-mediated glycogen turnover in chick astrocytes. J Neurochem 117(5):915–926
Acknowledgments
This study was supported by funding from NIH/NINDS (NS075177 and NS078304), the W. M. Keck Foundation, and the Dana Foundation. We thank Leif Hertz for comments on the manuscript.
Author information
Affiliations
Corresponding author
Additional information
Special Issue: In Honor of Leif Hertz.
John O’Donnell, Douglas Zeppenfeld, Evan McConnell and Salvador Pena contributed equally to the work.
Rights and permissions
About this article
Cite this article
O’Donnell, J., Zeppenfeld, D., McConnell, E. et al. Norepinephrine: A Neuromodulator That Boosts the Function of Multiple Cell Types to Optimize CNS Performance. Neurochem Res 37, 2496–2512 (2012). https://doi.org/10.1007/s11064-012-0818-x
Received:
Revised:
Accepted:
Published:
Issue Date:
Keywords
- Astrocyte
- Microglia
- Glycogen
- Potassium
- Inflammation
- Synaptic scaling