Left brain cortical activity modulates stress effects on social behavior

When subjected to stress, some individuals develop maladaptive symptoms whereas others retain normal behavior. The medial prefrontal cortex (mPFC) is known to control these adaptive responses to stress. Here, we show that mPFC neurons in the left hemisphere control stress effects on social behavior. Mice made socially avoidant by the stress of chronic social defeats showed depressed neural activity in the left mPFC. Photoactivation of these neurons reversed social avoidance and restored social activity. Despite social defeats, resilient mice with normal sociability showed normal firing rates in the left mPFC; however, photoinhibition of these neurons induced social avoidance. The same photomodulation administered to the right mPFC caused no significant effects. These results explain how stressed individuals develop maladaptive behaviors through left cortical depression, as reported in mood and anxiety disorders.

[1]  Y. Istefanopulos,et al.  IEEE Engineering in Medicine and Biology Society , 2019, IEEE Transactions on Biomedical Engineering.

[2]  D. Weiss,et al.  Predictors of posttraumatic stress disorder and symptoms in adults: a meta-analysis. , 2003, Psychological bulletin.

[3]  T. Michael,et al.  Age of traumatisation as a predictor of post-traumatic stress disorder or major depression in young women , 2004, British Journal of Psychiatry.

[4]  K. Deisseroth,et al.  Molecular and Cellular Approaches for Diversifying and Extending Optogenetics , 2010, Cell.

[5]  M. Herkenham,et al.  Environmental Enrichment Confers Stress Resiliency to Social Defeat through an Infralimbic Cortex-Dependent Neuroanatomical Pathway , 2011, The Journal of Neuroscience.

[6]  C. Nemeroff,et al.  The role of childhood trauma in the neurobiology of mood and anxiety disorders: preclinical and clinical studies , 2001, Biological Psychiatry.

[7]  B. Bunney,et al.  Dopamine and norepinephrine innervated cells in the rat prefrontal cortex: pharmacological differentiation using microiontophoretic techniques. , 1976, Life sciences.

[8]  S. Shelton,et al.  Asymmetric frontal brain activity, cortisol, and behavior associated with fearful temperament in rhesus monkeys. , 1998, Behavioral neuroscience.

[9]  John W. Lane,et al.  Marking microelectrode penetrations with fluorescent dyes , 1996, Journal of Neuroscience Methods.

[10]  B. M. Spruijt,et al.  Isolation during the play period in infancy decreases adult social interactions in rats , 1999, Behavioural Brain Research.

[11]  Klaus Mattes,et al.  Altered tonic and phasic cortisol secretion following unilateral stroke , 2009, Psychoneuroendocrinology.

[12]  A. Bartolomucci,et al.  Stress and Depression: Preclinical Research and Clinical Implications , 2009, PloS one.

[13]  P. Boesiger,et al.  Imbalance between Left and Right Dorsolateral Prefrontal Cortex in Major Depression Is Linked to Negative Emotional Judgment: An fMRI Study in Severe Major Depressive Disorder , 2008, Biological Psychiatry.

[14]  Jan Sijbers,et al.  Magnetic Resonance Imaging and Spectroscopy Reveal Differential Hippocampal Changes in Anhedonic and Resilient Subtypes of the Chronic Mild Stress Rat Model , 2011, Biological Psychiatry.

[15]  P. Gass,et al.  Learned helplessness: validity and reliability of depressive-like states in mice. , 2005, Brain research. Brain research protocols.

[16]  Karl Deisseroth,et al.  Optogenetics in Neural Systems , 2011, Neuron.

[17]  R. Kessler,et al.  The effects of stressful life events on depression. , 1997, Annual review of psychology.

[18]  Etienne Audinat,et al.  Excitation of rat prefrontal cortical neurons by dopamine: An in vitro electrophysiological study , 1987, Brain Research.

[19]  Benjamin R. Arenkiel,et al.  Synaptic Modifications in the Medial Prefrontal Cortex in Susceptibility and Resilience to Stress , 2014, The Journal of Neuroscience.

[20]  A. Masten.  Ordinary magic. Resilience processes in development. , 2001, The American psychologist.

[21]  Christofer Toumazou,et al.  High-frequency limit of neural stimulation with ChR2 , 2011, 2011 Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[22]  R. Neve,et al.  Enhancing Depression Mechanisms in Midbrain Dopamine Neurons Achieves Homeostatic Resilience , 2014, Science.

[23]  R. Sullivan,et al.  Lateralized Effects of Medial Prefrontal Cortex Lesions on Neuroendocrine and Autonomic Stress Responses in Rats , 1999, The Journal of Neuroscience.

[24]  K. Deisseroth,et al.  A prefrontal cortex–brainstem neuronal projection that controls response to behavioural challenge , 2012, Nature.

[25]  Johannes Hewig,et al.  Associations of the cortisol awakening response (CAR) with cortical activation asymmetry during the course of an exam stress period , 2008, Psychoneuroendocrinology.

[26]  B. Lewis,et al.  Ventral tegmental area afferents to the prefrontal cortex maintain membrane potential 'up' states in pyramidal neurons via D(1) dopamine receptors. , 2000, Cerebral cortex.

[27]  Scott J. Russo,et al.  Molecular Adaptations Underlying Susceptibility and Resistance to Social Defeat in Brain Reward Regions , 2007, Cell.

[28]  George A. Bonanno.  Loss, trauma, and human resilience: Have we underestimated the human capacity to thrive after extremely aversive events? , 2008 .

[29]  Danielle L. Graham,et al.  Essential Role of BDNF in the Mesolimbic Dopamine Pathway in Social Defeat Stress , 2006, Science.

[30]  Sean M Montgomery,et al.  Entrainment of Neocortical Neurons and Gamma Oscillations by the Hippocampal Theta Rhythm , 2008, Neuron.

[31]  E. Nestler,et al.  Prefrontal Cortical Circuit for Depression- and Anxiety-Related Behaviors Mediated by Cholecystokinin: Role of ΔFosB , 2014, The Journal of Neuroscience.

[32]  E. Domenici,et al.  Chronic Social Stress Inhibits Cell Proliferation in the Adult Medial Prefrontal Cortex: Hemispheric Asymmetry and Reversal by Fluoxetine Treatment , 2007, Neuropsychopharmacology.

[33]  Collin Challis,et al.  Optogenetic modulation of descending prefrontocortical inputs to the dorsal raphe bidirectionally bias socioaffective choices after social defeat , 2014, Front. Behav. Neurosci..

[34]  A. Zangen,et al.  Resilience to Chronic Stress Is Mediated by Hippocampal Brain-Derived Neurotrophic Factor , 2011, The Journal of Neuroscience.

[35]  W. Drevets.  Neuroimaging studies of mood disorders , 2000, Biological Psychiatry.

[36]  K. J. Parker,et al.  Neuroendocrine aspects of hypercortisolism in major depression , 2003, Hormones and Behavior.

[37]  J. Glowinski,et al.  Dopaminergic Terminals in the Rat Cortex , 1973, Science.

[38]  R. Sullivan,et al.  Hemispheric Asymmetry in Stress Processing in Rat Prefrontal Cortex and the Role of Mesocortical Dopamine , 2004, Stress.

[39]  Karen J. Ferguson,et al.  Smaller left anterior cingulate cortex volumes are associated with impaired hypothalamic-pituitary-adrenal axis regulation in healthy elderly men. , 2006, The Journal of clinical endocrinology and metabolism.

[40]  Suzanne R. Best,et al.  Predictors of posttraumatic stress disorder and symptoms in adults: a meta-analysis. , 2008, Psychological bulletin.

[41]  George Paxinos,et al.  The Mouse Brain in Stereotaxic Coordinates , 2001 .

[42]  G. Miller,et al.  Depression and Hypothalamic-Pituitary-Adrenal Activation: A Quantitative Summary of Four Decades of Research , 2011, Psychosomatic medicine.

[43]  Lief E. Fenno,et al.  Neocortical excitation/inhibition balance in information processing and social dysfunction , 2011, Nature.

[44]  S. Russo,et al.  A standardized protocol for repeated social defeat stress in mice , 2011, Nature Protocols.

[45]  D P Auer,et al.  Corticosteroid status influences the volume of the rat cingulate cortex - a magnetic resonance imaging study. , 2005, Journal of psychiatric research.

[46]  M. Raichle,et al.  Subgenual prefrontal cortex abnormalities in mood disorders , 1997, Nature.

[47]  Mary Kay Lobo,et al.  Antidepressant Effect of Optogenetic Stimulation of the Medial Prefrontal Cortex , 2010, The Journal of Neuroscience.

[48]  K. Dzirasa,et al.  Prefrontal cortex reactivity underlies trait vulnerability to chronic social defeat stress , 2014, Nature Communications.

[49]  K. Kendler,et al.  Causal relationship between stressful life events and the onset of major depression. , 1999, The American journal of psychiatry.

[50]  E. Bamberg,et al.  Light Activation of Channelrhodopsin-2 in Excitable Cells of Caenorhabditis elegans Triggers Rapid Behavioral Responses , 2005, Current Biology.

[51]  E. F. Espejo.  Prefrontocortical Dopamine Loss in Rats Delays Long-Term Extinction of Contextual Conditioned Fear, and Reduces Social Interaction Without Affecting Short-Term Social Interaction Memory , 2003, Neuropsychopharmacology.

[52]  J. Detre,et al.  Perfusion functional MRI reveals cerebral blood flow pattern under psychological stress. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[53]  A. B. Silva-Gómez,et al.  Decreased dendritic spine density on prefrontal cortical and hippocampal pyramidal neurons in postweaning social isolation rats , 2003, Brain Research.

[54]  K. Deisseroth,et al.  Rapid regulation of depression-related behaviors by control of midbrain dopamine neurons , 2012, Nature.

[55]  Bruce S. McEwen,et al.  Psychobiological allostasis: resistance, resilience and vulnerability , 2011, Trends in Cognitive Sciences.

[56]  M. Barrot,et al.  Induction of ΔFosB in the Periaqueductal Gray by Stress Promotes Active Coping Responses , 2007, Neuron.