Selective activation of dorsal raphe nucleus-projecting neurons in the ventral medial prefrontal cortex by controllable stress.
Exposure to uncontrollable stressors produces a variety of behavioral consequences (e.g. exaggerated fear, reduced social exploration) that do not occur if the stressor is controllable. In addition, an initial experience with a controllable stressor can block the behavioral and neural responses to a later uncontrollable stressor. The serotonergic (5-HT) dorsal raphe nucleus (DRN) has come to be viewed as a critical structure in mediating the behavioral effects of uncontrollable stress. Recent work suggests that the buffering effects of behavioral control on the DRN-dependent behavioral outcomes of uncontrollable stress require ventral medial prefrontal cortex (mPFCv) activation at the time of behavioral control. The present studies were conducted to directly determine whether or not controllable stress selectively activates DRN-projecting neurons within the mPFCv. To examine this possibility in the rat, we combined retrograde tracing (fluorogold iontophoresed into the DRN) with Fos immunohistochemistry, a marker for neural activation. Exposure to controllable, relative to uncontrollable, stress increased Fos expression in fluorogold-labeled neurons in the prelimbic region (PL) of the mPFCv. Furthermore, in a separate experiment, a prior experience with controllable stress led to potentiation of Fos expression in retrogradely labeled PL neurons in response to an uncontrollable stressor 1 week later. These results suggest that the PL selectively responds to behavioral control and utilizes such information to regulate the brainstem response to ongoing and subsequent stressors.
Baratta
Michael V
MV
Department of Psychology, University of Colorado at Boulder, Boulder, CO 80309-0345, USA. baratta@mit.edu
Zarza
Christina M
CM
Gomez
Devan M
DM
Campeau
Serge
S
Watkins
Linda R
LR
Maier
Steven F
SF
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D004597:Electroshock; D005456:Fluorescent Dyes; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008297:Male; D009434:Neural Pathways / Q000378:metabolism / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D017397:Prefrontal Cortex / Q000378:metabolism / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011903:Raphe Nuclei / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000502:physiology*
D005456:Fluorescent Dyes; D016760:Proto-Oncogene Proteins c-fos
Brain Res. 1998 Nov 23;812(1-2):113-20
9813270
J Comp Neurol. 1989 Dec 8;290(2):213-42
2592611
Neuroscience. 2001;106(4):783-92
11682163
Am J Psychiatry. 1998 May;155(5):630-7
9585714
Neuroscience. 2007 Jun 8;146(4):1495-503
17478046
Synapse. 2004 Jan;51(1):32-58
14579424
J Comp Neurol. 2005 Jan 10;481(2):179-93
15562508
Neuroscience. 1998 Nov;87(1):95-108
9722144
J Comp Physiol Psychol. 1968 Apr;65(2):251-60
5668311
Neuropsychopharmacology. 2009 Mar;34(4):834-43
18368036
Brain Res. 1999 Apr 24;826(1):35-43
10216194
Brain Res. 1997 Sep 12;768(1-2):327-32
9369332
Neurosci Biobehav Rev. 2005;29(4-5):829-41
15893820
Nat Neurosci. 2005 Mar;8(3):365-71
15696163
Neuropsychopharmacology. 1988 Dec;1(4):287-95
2908021
J Neurosci. 2006 Dec 20;26(51):13264-72
17182776
Brain Res Bull. 1992 Dec;29(6):943-8
1473026
J Neurosci Methods. 1980 Dec;3(2):129-49
6110810
J Neurosci. 2001 Dec 15;21(24):9917-29
11739599
Ciba Found Symp. 1986;123:191-215
3028724
Neuroscience. 1998 Mar;83(1):63-79
9466399
Brain Res. 1998 Feb 2;783(1):115-20
9479059
Am J Psychiatry. 2004 Feb;161(2):195-216
14754765
Physiol Rev. 1992 Jan;72(1):165-229
1731370
J Comp Neurol. 2005 Nov 14;492(2):145-77
16196030
Ann N Y Acad Sci. 2006 Jul;1071:379-96
16891584
J Comp Neurol. 2004 Jan 19;468(4):518-29
14689484
Brain Res Bull. 2009 Mar 16;78(4-5):240-7
19103268
Neuroscience. 2008 Jul 17;154(4):1178-86
18515010
Brain Res. 2009 Aug 18;1285:109-18
19524553