Discrete forebrain neuronal networks supporting noradrenergic regulation of sensorimotor gating.
Prepulse inhibition (PPI) refers to the reduction in the startle response when a startling stimulus is preceded by a weak prestimulus, and is an endophenotype of deficient sensorimotor gating in several neuropsychiatric disorders. Emerging evidence suggests that norepinephrine (NE) regulates PPI, however, the circuitry involved is unknown. We found recently that stimulation of the locus coeruleus (LC), the primary source of NE to the forebrain, induces a PPI deficit that is a result of downstream NE release. Hence, this study sought to identify LC-innervated forebrain regions that mediate this effect. Separate groups of male Sprague-Dawley rats received a cocktail solution of the α1-NE receptor agonist phenylephrine plus the β-receptor agonist isoproterenol (equal parts of each; 0, 3, 10, and 30 μg) into subregions of the medial prefrontal cortex (mPFC), nucleus accumbens (NAcc), extended amygdala, mediodorsal thalamus (MD-thalamus), or the dorsal hippocampus (DH) before PPI testing. NE agonist infusion into the posterior mPFC, NAcc shell, bed nucleus of the stria terminalis, basolateral amygdala, and the MD-thalamus disrupted PPI, with particularly strong effects in MD-thalamus. Sites in which NE receptor stimulation did not disrupt PPI (anterior mPFC, NAcc core, central amygdala, and DH) did support PPI disruptions with the dopamine D2 receptor agonist quinpirole (0, 10 μg). This pattern reveals new pathways in the regulation of PPI, and suggests that NE transmission within distinct thalamocortical and ventral forebrain networks may subserve the sensorimotor gating deficits that are seen in disorders such as schizophrenia, Tourette syndrome, and post-traumatic stress disorder.
Department of Psychiatry and Neuroscience Training Program, University of Wisconsin, Madison, WI, USA.
Karen M
KM
Alsene
Abha K
AK
Rajbhandari
Marcia J
MJ
Ramaker
Vaishali P
VP
Bakshi
D000161:Acoustic Stimulation / Q000009:adverse effects; D018663:Adrenergic Agents / Q000494:pharmacology; D000679:Amygdala / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001931:Brain Mapping; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004347:Drug Interactions; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism*; D016548:Prosencephalon / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D011571:Psychoacoustics; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology*; D055139:Sensory Gating / Q000187:drug effects / Q000502:physiology*
D018663:Adrenergic Agents; D018491:Dopamine Agonists; D004338:Drug Combinations; D019257:Quinpirole; D009638:Norepinephrine
Psychopharmacology (Berl). 2001 Jul;156(2-3):234-58
11549226
J Comp Neurol. 1975 Oct 15;163(4):467-505
1100685
Am J Psychiatry. 1990 Nov;147(11):1467-70
2221157
J Neurosci. 1998 Apr 15;18(8):3035-42
9526020
Nutr Neurosci. 2007 Jun-Aug;10(3-4):151-7
18019397
Neuropsychopharmacology. 1995 Feb;12(1):73-86
7766289
Acta Psychiatr Scand. 2009 Nov;120(5):345-54
19807715
World Psychiatry. 2008 Feb;7(1):11-8
18458787
Psychiatry Res. 1996 Oct 16;64(3):169-78
8944395
Arch Gen Psychiatry. 1993 Apr;50(4):266-74
8466387
J Neurosci. 1994 Jul;14(7):4252-68
8027777
J Comp Neurol. 2003 Sep 15;464(2):220-37
12898614
Synapse. 1997 Nov;27(3):230-41
9329158
Annu Rev Neurosci. 2009;32:267-87
19555290
Nat Rev Neurosci. 2009 Mar;10(3):211-23
19190638
Eur J Pharmacol. 1999 May 7;372(1):9-16
10374709
Dialogues Clin Neurosci. 2009;11(3):269-80
19877495
Neuroscience. 1996 Apr;71(4):1031-5
8684606
Neurobiol Learn Mem. 2010 May;93(4):455-62
20064624
Neurobiol Learn Mem. 2007 Sep;88(2):260-3
17540584
Neuropsychopharmacology. 1996 Feb;14(2):87-96
8822531
CNS Spectr. 2001 Aug;6(8):656-62
15520613
Neuroscience. 2009 Feb 18;158(4):1530-40
19068224
Brain Res Rev. 2008 Jun;58(1):1-17
18199483
J Comp Neurol. 1988 Nov 8;277(2):195-213
2466057
Brain Res Brain Res Rev. 2003 Apr;42(1):33-84
12668290
Brain Res Bull. 1997;43(2):219-28
9222535
Neuroscience. 2002;113(2):289-99
12127086
Psychopharmacology (Berl). 2001 Jul;156(2-3):117-54
11549216
Exp Brain Res. 1993;97(1):71-82
8131833
Psychopharmacology (Berl). 2008 Aug;199(3):331-88
18568339
Arch Gen Psychiatry. 1991 Apr;48(4):324-8
2009034
Brain Res. 1998 Sep 28;806(2):127-40
9739125
J Neurosci. 2004 Sep 15;24(37):8161-9
15371517
Neurobiol Learn Mem. 2008 Jan;89(1):47-60
17964820
Biol Psychiatry. 1996 Jan 1;39(1):33-41
8719124
Neuroscience. 2006 Feb;137(3):1039-49
16298081
Biol Psychiatry. 1999 Jan 1;45(1):26-31
9894572
Arch Ital Biol. 2006 Aug;144(3-4):173-96
16977832
Neuropharmacology. 1998;37(3):401-4
9681939
Med Clin North Am. 2001 May;85(3):735-55
11349482
Adv Pharmacol. 1998;42:764-7
9328010
Psychopharmacology (Berl). 2006 Jun;186(2):246-54
16583235
Behav Neurosci. 2003 Apr;117(2):350-9
12708531
Psychopharmacology (Berl). 2001 Jul;156(2-3):194-215
11549223
J Comp Neurol. 2005 Nov 14;492(2):145-77
16196030
J Psychiatry Neurosci. 2008 Nov;33(6):489-98
18982171
Kaibogaku Zasshi. 1998 Apr;73(2):93-106
9617075
Acta Neuropathol. 2009 Apr;117(4):347-68
18604544
J Comp Neurol. 2005 Sep 26;490(3):220-38
16082676
Psychopharmacology (Berl). 1988;94(4):507-14
3131796
Neuroscience. 1993 Nov;57(1):143-51
8278048
Neuropsychopharmacology. 2006 Oct;31(10):2150-61
16407904
Physiol Rev. 1983 Jul;63(3):844-914
6308694
Neurochem Int. 1982;4(6):473-90
20487902
J Comp Neurol. 2007 May 10;502(2):309-24
17348015
J Comp Neurol. 2003 May 5;459(3):301-26
12655512
Learn Mem. 2006 Nov-Dec;13(6):770-6
17101879
Neurotox Res. 2008 Aug;14(1):71-8
18790726
Neurobiol Learn Mem. 2008 Oct;90(3):576-9
18657626
Br J Psychiatry. 1980 Oct;137:346-51
6160894
J Comp Neurol. 2005 Dec 5;493(1):99-110
16254995
J Neural Transm (Vienna). 2009 Apr;116(4):389-94
19221691
Int J Neurosci. 1986 Nov;30(4):303-9
3025121
Biol Psychiatry. 2005 Dec 1;58(11):894-900
16043136
Psychopharmacology (Berl). 2004 Jun;174(1):25-31
15205875
Prog Brain Res. 1991;88:293-305
1726028
Neuroscience. 1999;94(1):287-304
10613519
Brain Struct Funct. 2007 Sep;212(2):149-79
17717690
Neuroscience. 2007 Jun 8;146(4):1772-84
17478051
Neuropsychopharmacology. 1999 Apr;20(4):311-21
10088132
Brain Res Bull. 2007 Mar 30;71(6):601-9
17292803
Neuroscience. 2001;103(4):1033-42
11301210
Mil Med. 2005 Jun;170(6):513-5
16001603
Proc Natl Acad Sci U S A. 1980 Mar;77(3):1696-700
6246501
J Med Assoc Thai. 2005 Sep;88 Suppl 4:S339-47
16623052
Psychopharmacology (Berl). 2001 Jul;156(2-3):216-24
11549224
Nature. 1982 Oct 7;299(5883):484-6
7121591
Neurosci Lett. 2004 Jan 23;355(1-2):5-8
14729221
Brain Res Bull. 1990 Sep;25(3):485-98
2292046
Pharmacol Rev. 1994 Jun;46(2):121-36
7938162
Brain Res. 2002 Oct 25;953(1-2):246-54
12384258
Brain Res. 2007 May 25;1147:105-23
17368434
Psychiatry Res. 1989 Jan;27(1):31-8
2537987
Trends Pharmacol Sci. 1996 Jul;17(7):245-55
8756183
Proc Natl Acad Sci U S A. 1984 Mar;81(5):1585-9
6324206
Brain Res. 1995 Feb 20;672(1-2):289-97
7749750
Neuropsychopharmacology. 2004 Jul;29(7):1282-93
15039766