Orexin/hypocretin modulation of the basal forebrain cholinergic system: Role in attention.
The basal forebrain cholinergic system (BFCS) plays a role in several aspects of attentional function. Activation of this system by different afferent inputs is likely to influence how attentional resources are allocated. While it has been recognized for some time that the hypothalamus is a significant source of projections to the basal forebrain, the phenotype(s) of these inputs and the conditions under which their regulation of the BFCS becomes functionally relevant are still unclear. The cell bodies of neurons expressing orexin/hypocretin neuropeptides are restricted to the lateral hypothalamus and contiguous perifornical area but have widespread projections, including to the basal forebrain. Orexin fibers and both orexin receptor subtypes are distributed in cholinergic parts of the basal forebrain, where application of orexin peptides increases cell activity and cortical acetylcholine release. Furthermore, disruption of orexin signaling in the basal forebrain impairs the cholinergic response to an appetitive stimulus. In this review, we propose that orexin inputs to the BFCS form an anatomical substrate for links between arousal and attention, and that these interactions might be particularly important as a means by which interoceptive cues bias allocation of attentional resources toward related exteroceptive stimuli. Dysfunction in orexin-acetylcholine interactions may play a role in the arousal and attentional deficits that accompany neurodegenerative conditions as diverse as drug addiction and age-related cognitive decline.
Fadel
J
J
Department of Pharmacology, Physiology and Neuroscience, University of South Carolina School of Medicine, 6439 Garners Ferry Road, Columbia, SC 29208, USA. jim.fadel@uscmed.sc.edu
Burk
J A
JA
D000109:Acetylcholine / Q000502:physiology*; D000818:Animals; D001143:Arousal / Q000502:physiology; D001288:Attention / Q000502:physiology*; D020532:Basal Nucleus of Meynert / Q000033:anatomy & histology / Q000502:physiology*; D002799:Cholinergic Fibers / Q000502:physiology; D006801:Humans; D007026:Hypothalamic Area, Lateral / Q000033:anatomy & histology / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D009434:Neural Pathways / Q000033:anatomy & histology / Q000502:physiology; D009479:Neuropeptides / Q000502:physiology*; D064446:Orexin Receptors; D000068797:Orexins; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D018013:Receptors, Neuropeptide / Q000502:physiology
D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D000109:Acetylcholine
Neuroscience. 2008 Sep 9;155(4):1212-20
18674591
Neuropsychopharmacology. 2006 Feb;31(2):384-95
15988471
J Comp Physiol Psychol. 1974 May;86(5):768-86
4833583
Behav Neurosci. 1998 Dec;112(6):1519-25
9926833
Neuroscience. 2005;130(2):541-7
15664710
J Comp Neurol. 1999 Dec 13;415(2):145-59
10545156
J Comp Neurol. 2003 Oct 27;465(4):593-603
12975818
Nature. 2005 Sep 22;437(7058):556-9
16100511
Neuropeptides. 2002 Apr-Jun;36(2-3):85-95
12359500
Brain Res. 2002 Mar 15;930(1-2):206-11
11879811
Sleep. 2003 Feb 1;26(1):36-43
12627730
Brain Res. 1989 Feb 13;479(2):225-40
2924157
J Comp Neurol. 2003 Sep 15;464(2):220-37
12898614
J Neurosci. 2004 Nov 17;24(46):10493-501
15548664
Arch Ital Biol. 2001 Apr;139(3):313-28
11330208
J Comp Neurol. 1990 Dec 22;302(4):824-52
1982006
J Comp Neurol. 1983 Feb 20;214(2):170-97
6841683
J Physiol. 1977 Oct;272(1):24P
412951
Regul Pept. 2002 Mar 15;104(1-3):105-10
11830284
Nat Med. 2000 Sep;6(9):991-7
10973318
J Neurosci. 2002 Jul 1;22(13):5282-6
12097478
Sleep Med Rev. 2005 Aug;9(4):231-41
15961331
Biol Psychol. 1997 Mar 21;45(1-3):57-71
9083644
Psychopharmacology (Berl). 2000 Sep;151(4):406-15
11026747
Neuropsychopharmacology. 2008 Jul;33(8):1779-97
17928814
Annu Rev Nutr. 2002;22:417-38
12055352
Behav Brain Res. 1996 Jan;74(1-2):91-103
8851918
J Comp Neurol. 2005 Jan 10;481(2):160-78
15562511
Neurology. 2005 Sep 27;65(6):892-7
16186530
Neurobiol Aging. 1988 Jan-Feb;9(1):22-3
3164094
Arch Ital Biol. 1968 Sep;106(3):283-93
5724423
Neuroscience. 2001;106(4):699-715
11682157
Proc Natl Acad Sci U S A. 2008 Dec 9;105(49):19480-5
19033203
Biogerontology. 2002;3(1-2):67-71
12014845
Neuron. 2000 Sep;27(3):469-74
11055430
J Neurosci. 2002 Aug 1;22(15):6742-6
12151553
Neurosci Lett. 2002 Nov 8;332(3):190-4
12399012
Nat Rev Neurosci. 2002 May;3(5):339-49
11988773
J Clin Exp Neuropsychol. 2005 Feb;27(2):189-204
15903150
Am J Physiol Regul Integr Comp Physiol. 2001 Feb;280(2):R598-601
11208592
Brain Res. 1989 Feb 6;479(1):177-84
2924147
Brain Res. 1979 Mar 23;164:121-35
106927
Neurosci Lett. 1982 Feb 12;28(2):217-22
7070710
J Comp Neurol. 2006 Feb 10;494(5):845-61
16374809
Trends Pharmacol Sci. 2006 Jul;27(7):368-74
16766052
J Comp Neurol. 1991 Apr 22;306(4):631-67
2071698
Neuron. 2005 Apr 21;46(2):297-308
15848807
Proc Natl Acad Sci U S A. 2005 Dec 27;102(52):19168-73
16357203
J Neurosci. 2001 Mar 1;21(5):1656-62
11222656
Regul Pept. 2002 Mar 15;104(1-3):145-51
11830289
Science. 1982 Mar 5;215(4537):1237-9
7058341
Eur J Neurosci. 2002 Jan;15(2):315-28
11849298
Cell. 1999 Aug 6;98(3):365-76
10458611
Science. 2007 Jan 26;315(5811):531-4
17255515
Neuroscience. 2001;105(4):899-909
11530228
J Neuroendocrinol. 1999 Aug;11(8):653-63
10447804
J Comp Neurol. 2001 Jun 18;435(1):1-5
11370007
Pharmacol Biochem Behav. 2008 Aug;90(2):156-62
18281084
Eur J Neurosci. 2000 Aug;12(8):3051-8
10971646
J Pharmacol Exp Ther. 2003 May;305(2):507-14
12606634
Arch Neurol. 2005 Jan;62(1):20-2
15642845
Psychopharmacology (Berl). 2009 Oct;206(2):205-13
19575184
Sleep. 1995 Jul;18(6):478-500
7481420
J Neurosci. 2001 Jul 1;21(13):4908-14
11425918
Peptides. 2003 Jun;24(6):925-30
12948846
Proc Natl Acad Sci U S A. 1998 Jan 6;95(1):322-7
9419374
Behav Brain Res. 2000 Nov;115(2):251-63
11000424
Neuroscience. 1983 Dec;10(4):1185-201
6320048
Brain Res Brain Res Rev. 1997 Feb;23(1-2):28-46
9063585
Anesthesiology. 2006 May;104(5):1023-32
16645455
Neurobiol Learn Mem. 2003 Nov;80(3):245-56
14521867
Brain Res. 2007 Jan 12;1128(1):107-19
17126820
Learn Mem. 2004 Jan-Feb;11(1):43-9
14747516
Lancet. 2000 Jan 1;355(9197):39-40
10615891
Brain Res Brain Res Rev. 2005 Feb;48(1):98-111
15708630
Neuroscience. 2007 Nov 9;149(3):499-507
17928158
Prog Brain Res. 1993;98:303-8
8248519
Neurobiol Aging. 2004 Feb;25(2):231-8
14749141
Biochem Biophys Res Commun. 2003 Mar 28;303(1):120-9
12646175
J Pharmacol Exp Ther. 2006 Apr;317(1):163-71
16352704
Am J Med Genet C Semin Med Genet. 2008 May 15;148C(2):89-98
18412102
J Comp Neurol. 2001 Jun 18;435(1):6-25
11370008
Brain Res Cogn Brain Res. 1997 Oct;6(2):147-58
9450608
Behav Brain Res. 1997 Feb;83(1-2):15-23
9062655
J Sleep Res. 2006 Sep;15(3):329-38
16911036
Peptides. 1999 Dec;20(12):1455-70
10698122
Neuron. 2006 Jun 1;50(5):711-22
16731510
Neuron. 2005 Jun 2;46(5):787-98
15924864
J Neurosci. 2002 Mar 1;22(5):1905-13
11880520
Brain Res Bull. 1982 Jun;8(6):727-49
6182962
Front Biosci. 2003 May 01;8:s438-51
12700104
Behav Brain Res. 2007 Oct 1;183(1):43-51
17599478
Eur J Neurosci. 2002 Jun;15(12):1867-73
12099892
Psychopharmacology (Berl). 1998 Jun;137(4):410-4
9676902
Ann Neurol. 1987 Jul;22(1):31-6
3307603
Neuroscience. 1997 Aug;79(4):1051-78
9219967
J Neurosci. 2005 Jul 13;25(28):6716-20
16014733
Neuron. 2004 Mar 25;41(6):969-82
15046728
Cell. 1998 Feb 20;92(4):573-85
9491897
Alzheimer Dis Assoc Disord. 1987;1(3):128-55
3331115
Neurology. 1994 Apr;44(4):657-62
8164820
Arch Neurol. 2006 Sep;63(9):1312-7
16966511
Eur J Pharmacol. 2006 Mar 27;535(1-3):172-6
16545369
Brain Res Bull. 2008 Dec 16;77(6):367-73
18950690
Exp Neurol. 1976 Nov;53(2):508-19
824153
Peptides. 2002 Sep;23(9):1683-8
12217429
J Neurosci. 2000 Nov 15;20(22):8620-8
11069971
Cell. 1999 Aug 20;98(4):437-51
10481909
Sleep. 2004 Aug 1;27(5):851-6
15453542
Synapse. 1995 Dec;21(4):324-31
8869162
Exp Brain Res. 1992;89(3):611-22
1644125
J Neurosci. 2004 Apr 7;24(14):3527-36
15071100
Psychopharmacology (Berl). 1999 May;144(2):175-82
10394999
Schizophr Bull. 2007 Nov;33(6):1284-90
17656637
Neuropharmacology. 2009;56 Suppl 1:107-11
18694770
Neuron. 2006 Feb 16;49(4):589-601
16476667
Prog Brain Res. 2004;145:207-31
14650918
Brain. 1984 Mar;107 ( Pt 1):253-74
6538106
J Neurosci. 1998 Dec 1;18(23):9996-10015
9822755
J Neurosci. 1999 Jan 1;19(1):248-57
9870955
Eur J Neurosci. 2004 Dec;20(11):3054-62
15579160
Neuroscience. 2002;111(2):379-87
11983323
Behav Neurosci. 1996 Apr;110(2):247-65
8731052
Exp Neurol. 1976 Jun;51(3):668-77
819286
Synapse. 1993 Jun;14(2):132-43
8392756
Neuroscience. 2001;103(3):777-97
11274794
Arch Neurol. 1994 Jul;51(7):682-8
8018041
Neuroscience. 2001;108(2):177-81
11734353
Horm Behav. 2000 Jun;37(4):335-44
10860677
Dement Geriatr Cogn Disord. 2002;13(1):46-58
11731715
Prog Brain Res. 2004;145:311-7
14650925
Neuroscience. 2003;119(4):1033-44
12831862
Neurosci Lett. 1989 May 22;100(1-3):198-202
2761770
Exp Clin Psychopharmacol. 2007 Dec;15(6):546-54
18179307
Brain Res Brain Res Rev. 2001 Apr;35(2):146-60
11336780
Schizophr Bull. 2005 Jan;31(1):117-38
15888431
Drug Alcohol Depend. 2008 Sep 1;97(1-2):1-20
18479844
Nat Rev Neurosci. 2002 Aug;3(8):655-66
12154366
Neuroscience. 2002;114(2):451-60
12204214
J Comp Neurol. 2002 Feb 4;443(2):136-53
11793352
Proc Natl Acad Sci U S A. 1999 Jan 19;96(2):748-53
9892705
Acta Physiol (Oxf). 2009 Jan;195(1):71-8
18983451
Eur J Neurosci. 2008 Oct;28(8):1545-56
18793323
Biol Psychiatry. 2009 May 15;65(10):857-62
19251246
J Comp Neurol. 1997 Jun 30;383(2):163-77
9182846
Psychopharmacology (Berl). 2003 Feb;165(4):346-58
12454730