Medial prefrontal cortex determines how stressor controllability affects behavior and dorsal raphe nucleus

The degree of behavioral control that an organism has over a stressor is a potent modulator of the stressor's impact; uncontrollable stressors produce numerous outcomes that do not occur if the stressor is controllable. Research on controllability has focused on brainstem nuclei such as the dorsal raphe nucleus (DRN). Here we find that the infralimbic and prelimbic regions of the ventral medial prefrontal cortex (mPFCv) in rats detect whether a stressor is under the organism's control. When a stressor is controllable, stress-induced activation of the DRN is inhibited by the mPFCv, and the behavioral sequelae of uncontrollable stress are blocked. This suggests a new function for the mPFCv and implies that the presence of control inhibits stress-induced neural activity in brainstem nuclei, in contrast to the prevalent view that such activity is induced by a lack of control.

[1]  M. Seligman,et al.  Failure to escape traumatic shock. , 1967, Journal of experimental psychology.

[2]  J. Weiss Effects of coping responses on stress. , 1968, Journal of comparative and physiological psychology.

[3]  G. Paxinos,et al.  The Rat Brain in Stereotaxic Coordinates , 1983 .

[4]  S. Maier Learned helplessness and animal models of depression , 1984, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[5]  J. Weiss,et al.  Depression in an animal model: focus on the locus ceruleus. , 2007, Ciba Foundation symposium.

[6]  M. Fanselow,et al.  Changes in feeding and foraging patterns as an antipredator defensive strategy: a laboratory simulation using aversive stimulation in a closed economy. , 1988, Journal of the experimental analysis of behavior.

[7]  S. Maier Role of fear in mediating shuttle escape learning deficit produced by inescapable shock. , 1990, Journal of experimental psychology. Animal behavior processes.

[8]  S. Maier,et al.  The role of the amygdala and dorsal raphe nucleus in mediating the behavioral consequences of inescapable shock. , 1993, Behavioral neuroscience.

[9]  J. Verbalis,et al.  c-Fos and Related Immediate Early Gene Products as Markers of Activity in Neuroendocrine Systems , 1993, Frontiers in Neuroendocrinology.

[10]  S. Maier,et al.  8-OH-DPAT microinjected in the region of the dorsal raphe nucleus blocks and reverses the enhancement of fear conditioning and interference with escape produced by exposure to inescapable shock. , 1995, Behavioral neuroscience.

[11]  F. Graeff,et al.  Role of 5-HT in stress, anxiety, and depression , 1996, Pharmacology Biochemistry and Behavior.

[12]  F. Mascagni,et al.  Projections of the medial and lateral prefrontal cortices to the amygdala: a Phaseolus vulgaris leucoagglutinin study in the rat , 1996, Neuroscience.

[13]  F. Mascagni,et al.  Projections of the lateral entorhinal cortex to the amygdala: a Phaseolus vulgaris leucoagglutinin study in the rat , 1997, Neuroscience.

[14]  C. Rampon,et al.  Forebrain afferents to the rat dorsal raphe nucleus demonstrated by retrograde and anterograde tracing methods , 1997, Neuroscience.

[15]  M. Hajós,et al.  An electrophysiological and neuroanatomical study of the medial prefrontal cortical projection to the midbrain raphe nuclei in the rat , 1998, Neuroscience.

[16]  S. Maier,et al.  Exposure to inescapable but not escapable shock increases extracellular levels of 5-HT in the dorsal raphe nucleus of the rat , 1998, Brain Research.

[17]  B. Balleine,et al.  Goal-directed instrumental action: contingency and incentive learning and their cortical substrates , 1998, Neuropharmacology.

[18]  S. Maier,et al.  Escapable and inescapable stress differentially alter extracellular levels of 5-HT in the basolateral amygdala of the rat , 1998, Brain Research.

[19]  M. Basoglu Torture and its Consequences: Current Treatment Approaches , 1999 .

[20]  S. Maier,et al.  Activation of serotonin-immunoreactive cells in the dorsal raphe nucleus in rats exposed to an uncontrollable stressor , 1999, Brain Research.

[21]  Lawrence H Staib,et al.  Neural correlates of exposure to traumatic pictures and sound in Vietnam combat veterans with and without posttraumatic stress disorder: a positron emission tomography study , 1999, Biological Psychiatry.

[22]  R Tao,et al.  Differential effect of local infusion of serotonin reuptake inhibitors in the raphe versus forebrain and the role of depolarization-induced release in increased extracellular serotonin. , 2000, The Journal of pharmacology and experimental therapeutics.

[23]  G. Quirk,et al.  The Role of Ventromedial Prefrontal Cortex in the Recovery of Extinguished Fear , 2000, The Journal of Neuroscience.

[24]  T. Robbins,et al.  From arousal to cognition: the integrative position of the prefrontal cortex. , 2000, Progress in brain research.

[25]  E. Miller,et al.  An integrative theory of prefrontal cortex function. , 2001, Annual review of neuroscience.

[26]  S. Maier,et al.  The role of the habenular complex in the elevation of dorsal raphe nucleus serotonin and the changes in the behavioral responses produced by uncontrollable stress , 2001, Brain Research.

[27]  S. Maier,et al.  Blockade of alpha1 adrenoreceptors in the dorsal raphe nucleus prevents enhanced conditioned fear and impaired escape performance following uncontrollable stressor exposure in rats , 2002, Behavioural Brain Research.

[28]  D. Stuss,et al.  Principles of frontal lobe function , 2002 .

[29]  G. Quirk Memory for extinction of conditioned fear is long-lasting and persists following spontaneous recovery. , 2002, Learning & memory.

[30]  R. Davidson Anxiety and affective style: role of prefrontal cortex and amygdala , 2002, Biological Psychiatry.

[31]  M. Mesulam,et al.  The human frontal lobes: Transcending the default mode through contingent encoding. , 2002 .

[32]  S. Royer,et al.  Bidirectional synaptic plasticity in intercalated amygdala neurons and the extinction of conditioned fear responses , 2002, Neuroscience.

[33]  S. Maier,et al.  Stressor Controllability Modulates Stress-Induced Dopamine and Serotonin Efflux and Morphine-Induced Serotonin Efflux in the Medial Prefrontal Cortex , 2003, Neuropsychopharmacology.

[34]  G. Quirk,et al.  Inhibition of the Amygdala: Key to Pathological States? , 2003, Annals of the New York Academy of Sciences.

[35]  Joseph E LeDoux,et al.  Ventral medial prefrontal cortex and emotional perseveration: the memory for prior extinction training , 2003, Behavioural Brain Research.

[36]  S. Maier,et al.  Stressor controllability modulates stress‐induced serotonin but not dopamine efflux in the nucleus accumbens shell , 2003, Synapse.

[37]  B. Balleine,et al.  The role of prelimbic cortex in instrumental conditioning , 2003, Behavioural Brain Research.

[38]  K. Jellinger Principles of frontal lobe function , 2003 .

[39]  J. Weiss,et al.  Stress-induced depression of motor activity correlates with regional changes in brain norepinephrine but not in dopamine , 2004, Neurochemical Research.

[40]  S. Maier,et al.  Stressor Controllability, Anxiety, and Serotonin , 1998, Cognitive Therapy and Research.

[41]  B. Balleine,et al.  Lesions of dorsolateral striatum preserve outcome expectancy but disrupt habit formation in instrumental learning , 2004, The European journal of neuroscience.

[42]  S. Sesack,et al.  Prefrontal cortical projections to the rat dorsal raphe nucleus: Ultrastructural features and associations with serotonin and γ‐aminobutyric acid neurons , 2004, The Journal of comparative neurology.

[43]  R. Vertes Differential projections of the infralimbic and prelimbic cortex in the rat , 2004, Synapse.

[44]  P. Celada,et al.  Modulation of the activity of pyramidal neurons in rat prefrontal cortex by raphe stimulation in vivo: involvement of serotonin and GABA. , 2004, Cerebral cortex.