Behave: The Biology of Humans at Our Best and Worst

by Robert M. Sapolsky

  81.K. Starcke et al., “Does Everyday Stress Alter Moral Decision-Making?” PNE 36 (2011): 210; F. Youssef et al., “Stress Alters Personal Moral Decision Making,” PNE 37 (2012): 491.

  82.D. Langford et al., “Social Modulation of Pain as Evidence for Empathy in Mice,” Sci 312 (2006): 1967.

  83.S. Taylor et al., “Biobehavioral Responses to Stress in Females: Tend-and-Befriend, Not Fight-or-Flight,” Psych Rev 107 (2000): 411.

  84.B. Bushman, “Human Aggression While Under the Influence of Alcohol and Other Drugs: An Integrative Research Review,” Curr Dir Psych Sci 2 (1993): 148; L. Zhang et al., “The Nexus Between Alcohol and Violent Crime,” Alcoholism: Clin and Exp Res 21 (1997): 1264; K. Graham and P. West, “Alcohol and Crime: Examining the Link,” in International Handbook of Alcohol Dependence and Problems, ed. N. Heather, T. J. Peters, and T. Stockwell (New York: John Wiley & Sons, 2001); I. Quadros et al., “Individual Vulnerability to Escalated Aggressive Behavior by a Low Dose of Alcohol: Decreased Serotonin Receptor mRNA in the Prefrontal Cortex of Male Mice,” Genes, Brain and Behav 9 (2010): 110; A. Johansson et al., “Alcohol and Aggressive Behavior in Men: Moderating Effects of Oxytocin Receptor Gene (OXTR) Polymorphisms,” Genes, Brain and Behav 11 (2012): 214.

  Chapter 5: Days to Months Before

  1.D. O. Hebb, The Organization of Behaviour (Hoboken, NJ: John Wiley & Sons, 1949).

  2.General reviews: R. Nicoll and K. Roche, “Long-Term Potentiation: Peeling the Onion,” Neuropharmacology 74 (2013): 18; J. MacDonald et al., “Hippocampal Long-Term Synaptic Plasticity and Signal Amplification of NMDA Receptors,” Critical Rev in Neurobiol 18 (2006): 71.

  3.T. Sigurdsson et al., “Long-Term Potentiation in the Amygdala: A Cellular Mechanism of Fear Learning and Memory,” Neuropharmacology 52 (2007): 215; J. Kim and M. Jung, “Neural Circuits and Mechanisms Involved in Pavlovian Fear Conditioning: A Critical Review,” Nsci Biobehav Rev 30 (2006): 188; M. Wolf, “LTP May Trigger Addiction,” Mol Interventions 3 (2003): 248; M. Wolf et al., “Psychomotor Stimulants and Neuronal Plasticity,” Neuropharmacology 47, supp. 1 (2004): 61.

  4.M. Foy et al., “17beta-estradiol Enhances NMDA Receptor-Mediated EPSPs and Long-Term Potentiation,” J Neurophysiology 81 (1999): 925; Y. Lin et al., “Oxytocin Promotes Long-Term Potentiation by Enhancing Epidermal Growth Factor Receptor-Mediated Local Translation of Protein Kinase Mζ,” J Nsci 32 (2012): 15476; K. Tomizawa et al., “Oxytocin Improves Long-Lasting Spatial Memory During Motherhood Through MAP Kinase Cascade,” Nat Nsci 6 (2003): 384; V. Skucas et al., “Testosterone Depletion in Adult Male Rats Increases Mossy Fiber Transmission, LTP, and Sprouting in Area CA3 of Hippocampus,” J Nsci 33 (2013): 2338; W. Timmermans et al., “Stress and Excitatory Synapses: From Health to Disease,” Nsci 248 (2013): 626.

  5.S. Rodrigues et al., “The Influence of Stress Hormones on Fear Circuitry,” Ann Rev Nsci 32 (2009): 289; X. Xu and Z. Zhang, “Effects of Estradiol Benzoate on Learning-Memory Behavior and Synaptic Structure in Ovariectomized Mice,” Life Sci 79 (2006): 1553; C. Rocher et al., “Acute Stress-Induced Changes in Hippocampal/Prefrontal Circuits in Rats: Effects of Antidepressants,” Cerebral Cortex 14 (2004): 224.

  6.A. Holtmaat and K. Svoboda, “Experience-Dependent Structural Synaptic Plasticity in the Mammalian Brain,” Nat Rev Nsci 10 (2009): 647; C. Woolley et al., “Naturally Occurring Fluctuation in Dendritic Spine Density on Adult Hippocampal Pyramidal Neurons,” J Nsci 10 (1990): 4035; W. Kelsch et al., “Watching Synaptogenesis in the Adult Brain,” Ann Rev of Nsci 33 (2010): 131.

  7.B. Leuner and T. Shors, “Stress, Anxiety, and Dendritic Spines: What Are the Connections?” Nsci 251 (2013): 108; Y. Chen et al., “Correlated Memory Defects and Hippocampal Dendritic Spine Loss After Acute Stress Involve Corticotropin-Releasing Hormone Signaling,” PNAS 107 (2010): 13123.

  8.J. Cerqueira et al., “Morphological Correlates of Corticosteroid-Induced Changes in Prefrontal Cortex Dependent Behaviours,” J Nsci 25 (2005): 7792; A. Izquierdo et al., “Brief Uncontrollable Stress Causes Dendritic Retraction in Infralimbic Cortex and Resistance to Fear Extinction in Mice,” J Nsci 26 (2006): 5733; C. Liston et al., “Stress-Induced Alterations in Prefrontal Cortical Dendritic Morphology Predict Selective Impairments in Perceptual Attentional Set Shifting,” J Nsci 26 (2006): 7870; J. Radley, “Repeated Stress Induces Dendritic Spine Loss in the Rat Medial Prefrontal Cortex,” Cerebral Cortex 16 (2006): 313; A. Arnsten, “Stress Signaling Pathways That Impair Prefrontal Cortex Structure and Function,” Nat Rev Nsci 10 (2009): 410; C. Sandi and M. Loscertales, “Opposite Effects on NCAM Expression in the Rat Frontal Cortex Induced by Acute vs. Chronic Corticosterone Treatments,” Brain Res 828 (1999): 127; C. Wellman, “Dendritic Reorganization in Pyramidal Neurons in Medial Prefrontal Cortex After Chronic Corticosterone Administration,” J Neurobiol 49 (2001): 245; D. Knox et al., “Single Prolonged Stress Decreases Glutamate, Glutamine, and Creatine Concentrations in the Rat Medial Prefrontal Cortex,” Nsci Lett 480 (2010): 16.

  9.E. Dias-Ferreira et al., “Chronic Stress Causes Frontostriatal Reorganization and Affects Decision-Making,” Sci 325 (2009): 621; M. Fuchikiami et al., “Epigenetic Regulation of BDNF Gene in Response to Stress,” Psychiatry Investigation 7 (2010): 251.

  10.R. Mitra and R. Sapolsky, “Acute Corticosterone Treatment Is Sufficient to Induce Anxiety and Amygdaloid Dendritic Hypertrophy,” PNAS 105 (2008): 5573; A. Vyas et al., “Chronic Stress Induces Contrasting Patterns of Dendritic Remodeling in Hippocampal and Amygdaloid Neurons,” J Nsci 22 (2002): 6810; S. Bennur et al., “Stress-Induced Spine Loss in the Medial Amygdala Is Mediated by Tissue-Plasminogen Activator,” Nsci 144 (2006): 8; A. Govindarajan et al., “Transgenic Brain-Derived Neurotrophic Factor Expression Causes Both Anxiogenic and Antidepressant Effects,” PNAS 103 (2006): 13208.

  Expansion of the BNST: A. Vyas et al., “Effects of Chronic Stress on Dendritic Arborization in the Central and Extended Amygdala,” Brain Res 965 (2003): 290; J. Pego et al., “Dissociation of the Morphological Correlates of Stress-Induced Anxiety and Fear,” Eur J Nsci 27 (2008): 1503.

  11.A. Magarinos and B. McEwen, “Stress-Induced Atrophy of Apical Dendrites of Hippocampal CA3c Neurons: Involvement of Glucocorticoid Secretion and Excitatory Amino Acid Receptors,” Nsci 69 (1995): 89; A. Magarinos et al., “Chronic Psychosocial Stress Causes Apical Dendritic Atrophy of Hippocampal CA3 Pyramidal Neurons in Subordinate Tree Shrews,” J Nsci 16 (1996): 3534; B. Eadie et al., “Voluntary Exercise Alters the Cytoarchitecture of the Adult Dentate Gyrus by Increasing Cellular Proliferation, Dendritic Complexity, and Spine Density,” J Comp Neurol 486 (2005): 39.

  12.M. Khan et al., “Estrogen Regulation of Spine Density and Excitatory Synapses in Rat Prefrontal and Somatosensory Cerebral Cortex,” Steroids 78 (2013): 614; B. McEwen, “Estrogen Actions Throughout the Brain,” Recent Prog Hormone Res 57 (2002): 357; B. Leuner and E. Gould, “Structural Plasticity and Hippocampal Function,” Ann Rev Psych 61 (2010): 111.

  13.R. Hamilton et al., “Alexia for Braille Following Bilateral Occipital Stroke in an Early Blind Woman,” Neuroreport 11 (2000): 237; E. Striem-Amit et al., “Reading with Sounds: Sensory Substitution Selectively Activates the Visual Word Form Area in the Blind,” Neuron 76 (2012): 640.

  14.S. Florence et al., “Large-Scale Sprouting of Cortical Connections After Peripheral Injury in Adult Macaque Monkeys,” Sci 282 (1998): 1117; C. Darian-Smith and C. Gilbert, “Axonal Sprouting Accompanies Functional Reorganization in Adult Cat Striate Cortex,” Nat 368 (1994): 737; M. Kossut and S. Juliano, “Anatomical Correlates of Representational Map Reorganization Induced by Partial Vibrissectomy in the Barrel Cortex of Adult Mice,” Nsci 92 (1999): 807; L. Merabet and A. Bascual-Leone, “Neural Reorganization Following Sensory Loss: The Opportunity of Change,” Nat Rev Nsci 11 (2010): 44; A. Pascual-Leone et al., “The Plastic Human Brain Cortex,” Ann Rev Nsci 28 (2005): 377; B. Becker et al., “Fear Processing and Social Networ
king in the Absence of a Functional Amygdala,” BP 72 (2012): 70; L. Colgin, “Understanding Memory Through Hippocampal Remapping,” TINS 31 (2008): 469; V. Ramirez-Amaya et al., “Spatial Longterm Memory Is Related to Mossy Fiber Synaptogenesis,” J Nsci 21 (2001): 7340; M. Holahan et al., “Spatial Learning Induces Presynaptic Structural Remodeling in the Hippocampal Mossy Fiber System of Two Rat Strains,” Hippocampus 16 (2006): 560; I. Galimberti et al., “Long-Term Rearrangements of Hippocampal Mossy Fiber Terminal Connectivity in the Adult Regulated by Experience,” Neuron 50 (2006): 749; V. De Paola et al., “Cell Type–Specific Structural plasticity of Axonal Branches and Boutons in the Adult Neocortex,” Neuron 49 (2006): 861; H. Nishiyama et al., “Axonal Motility and Its Modulation by Activity Are Branch-Type Specific in the Intact Adult Cerebellum,” Neuron 56 (2007): 472.

  15.C. Pantev and S. Herholz, “Plasticity of the Human Auditory Cortex Related to Musical Training,” Nsci Biobehav Rev 35 (2011): 2140.

  16.A. Pascual-Leone, “Reorganization of Cortical Motor Outputs in the Acquisition of New Motor Skills,” in Recent Advances in Clin Neurophysiology, ed. J. Kinura and H. Shibasaki (Amsterdam: Elsevier Science, 1996), pp. 304–8.

  17.C. Xerri et al., “Alterations of the Cortical Representation of the Rat Ventrum Induced by Nursing Behavior,” J Nsci 14 (1994): 171; B. Draganski et al., “Neuroplasticity: Changes in Grey Matter Induced by Training,” Nat 427 (2004): 311.

  18.J. Altman and G. Das, “Autoradiographic and Histological Evidence of Postnatal Hippocampal Neurogenesis in Rats,” J Comp Neurol 124 (1965): 319.

  19.M. Kaplan, “Environmental Complexity Stimulates Visual Cortex Neurogenesis: Death of a Dogma and a Research Career,” TINS 24 (2001): 617.

  20.S. Goldman and F. Nottebohm, “Neuronal Production, Migration, and Differentiation in a Vocal Control Nucleus of the Adult Female Canary Brain,” PNAS 80 (1983): 2390; J. Paton and F. Nottebohm, “Neurons Generated in the Adult Brain Are Recruited into Functional Circuits,” Sci 225 (1984): 4666; F. Nottebohm, “Neuronal Replacement in Adult Brain,” ANYAS 457 (1985): 143.

  For a great history of the entire neurogenesis saga, see M. Specter, “How the Songs of Canaries Upset a Fundamental Principle of Science,” New Yorker, July 23, 2001.

  21.D. Kornack and P. Rakic, “Continuation of Neurogenesis in the Hippocampus of the Adult Macaque Monkey,” PNAS 96 (1999): 5768.

  22.G. Ming and H. Song, “Adult Neurogenesis in the Mammalian Central Nervous System,” Ann Rev Nsci 28 (2005): 223. Rate of neuron replacement in the hippocampus: G. Kempermann et al., “More Hippocampal Neurons in Adult Mice Living in an Enriched Environment,” Nat 386 (1997): 493; H. Cameron and R. McKay, “Adult Neurogenesis Produces a Large Pool of New Granule Cells in the Dentate Gyrus,” J Comp Neurol 435 (2001): 406. Demonstration in humans: P. Eriksson et al., “Neurogenesis in the Adult Human Hippocampus,” Nat Med 4 (1998): 1313. Modulators of neurogenesis: C. Mirescu et al., “Sleep Deprivation Inhibits Adult Neurogenesis in the Hippocampus by Elevating Glucocorticoids,” PNAS 103 (2006): 19170. The role of new neurons in cognition: W. Deng et al., “New Neurons and New Memories: How Does Adult Hippocampal Neurogenesis Affect Learning and Memory?” Nat Rev Nsci 11 (2010): 339; T. Shors et al., “Neurogenesis in the Adult Rat Is Involved in the Formation of Trace Memories,” Nat 410 (2001): 372; T. Shors et al., “Neurogenesis May Relate to Some But Not All Types of Hippocampal-Dependent Learning,” Hippocampus 12 (2002): 578.

  23.Footnote regarding running, glucocorticoids and neurogenesis: S. Droste et al., “Effects of Long-Term Voluntary Exercise on the Mouse Hypothalamic-Pituitary-Adrenocortical Axis,” Endo 144 (2003): 3012; H. van Praag et al., “Running Enhances Neurogenesis, Learning, and Long-Term Potentiation in Mice,” PNAS 96 (1999): 13427; G. Kempermann, “New Neurons for ‘Survival of the Fittest,’” Nat Rev Nsci 13 (2012): 727.

  24.L. Santarelli et al., “Requirement of Hippocampal Neurogenesis for the Behavioral Effects of Antidepressants,” Sci 301 (2003): 80.

  25.J. Altmann, “The Discovery of Adult Mammalian Neurogenesis,” in Neurogenesis in the Adult Brain I, ed. T. Seki, K. Sawamoto, J. Parent, and A. Alvarez-Buylla (New York: Springer-Verlag, 2011).

  26.C. Lord et al., “Hippocampal Volumes Are Larger in Postmenopausal Women Using Estrogen Therapy Compared to Past Users, Never Users and Men: A Possible Window of Opportunity Effect,” Neurobiol of Aging 29 (2008): 95; R. Sapolsky, “Glucocorticoids and Hippocampal Atrophy in Neuropsychiatric Disorders,” AGP 57 (2000): 925; A. Mutso et al., “Abnormalities in Hippocampal Functioning with Persistent Pain,” J Nsci 32 (2012): 5747; J. Pruessner et al., “Stress Regulation in the Central Nervous System: Evidence from Structural and Functional Neuroimaging Studies in Human Populations,” PNE 35 (2010): 179; J. Kuo et al., “Amygdala Volume in Combat-Exposed Veterans With and Without Posttraumatic Stress Disorder: A Cross-sectional Study,” AGP 69 (2012): 1080.

  27.E. Maguire et al., “Navigation-Related Structural Change in the Hippocampi of Taxi Drivers,” PNAS 97 (2000): 4398; K. Woollett and E. Maguire, “Acquiring “the Knowledge” of London’s Layout Drives Structural Brain Changes,” Curr Biol 21 (2011): 2109. For an interesting discussion of why you need a bigger hippocampus to become a cab driver in London, revolving around the notoriously difficult licensing exam, see J. Rosen, “The Knowledge, London’s Legendary Taxi-Driver Test, Puts Up a Fight in the Age of GPS,” New York Times Magazine, November 10, 2014.

  28.S. Mangiavacchi et al., “Long-Term Behavioral and Neurochemical Effects of Chronic Stress Exposure in Rats,” J Neurochemistry 79 (2001): 1113; J. van Honk et al., “Baseline Salivary Cortisol Levels and Preconscious Selective Attention for Treat: A Pilot Study,” PNE 23 (1998): 741; M. Fuxjager et al., “Winning Territorial Disputes Selectively Enhances Androgen Sensitivity in Neural Pathways Related to Motivation and Social Aggression,” PNAS 107 (2010): 12393; I. McKenzie et al., “Motor Skill Learning Requires Active Central Myelination,” Sci 346 (2014): 318; M. Bechler and C. ffrench-Constant, “A New Wrap for Neuronal Activity?” Sci 344 (2014): 480; E. Gibson et al., “Neuronal Activity Promotes Oligodendrogenesis and Adaptive Myelination in the Mammalian Brain,” Sci 344 (2014): 487; J. Radley et al., “Reversibility of Apical Dendritic Retraction in the Rat Medial Prefrontal Cortex Following Repeated Stress,” Exp Neurol 196 (2005): 199; E. Bloss et al., “Interactive Effects of Stress and Aging on Structural Plasticity in the Prefrontal Cortex,” J Nsci 30 (2010): 6726.

  29.N. Doidge, The Brain That Changes Itself: Stories of Personal Triumph from the Front of Brain Science (New York: Penguin, 2007); S. Begley, Train Your Mind, Change Your Brain: How a New Science Reveals Our Extraordinary Potential to Transform Ourselves (New York: Ballantine Books, 2007); J. Arden, Rewire Your Brain: Think Your Way to a Better Life (New York: Wiley, 2010).

  Chapter 6: Adolescence; or, Dude, Where’s My Frontal Cortex?

  1.R. Knickmeyer et al., “A Structural MRI Study of Human Brain Development from Birth to 2 Years,” J Nsci 28 (2008): 12176.

  2.M. Bucholtz, “Youth and Cultural Practice,” Ann Rev Anthropology 31 (2002): 525; S. Choudhury, “Culturing the Adolescent Brain: What Can Neuroscience Learn from Anthropology?” SCAN 5 (2010): 159. Footnote: T. James, “The Age of Majority,” Am J Legal History 4 (1960): 22; R. Brett, “Contribution for Children and Political Violence,” in Child Soldiering: Questions and Challenges for Health Professionals (WHO Global Report on Violence), 2000, p. 1; C. MacMullin and M. Loughry, “Investigating Psychosocial Adjustment of Former Child Soldiers in Sierra Leone and Uganda,” J Refugee Studies 17 (2004): 472.

  3.J. Giedd, “The Teen Brain: Insights from Neuroimaging,” J Adolescent Health 42 (2008): 335. Demonstration of increased intrinsic connectivity of PFC neurons during adolescence in monkeys: X. Zhou et al., “Age-Dependent Changes in Prefrontal Intrinsic Connectivity,” PNAS 111 (2014): 3853; T. Singer, “The Neuronal Basis and Ontogeny of Empathy and Mind Reading: Review of Lite
rature and Implications for Future Research,” Nsci Biobehav Rev 30 (2006): 855; P. Shaw et al., “Intellectual Ability and Cortical Development in Children and Adolescents,” Nat 440 (2006): 676.

  4.D. Yurelun-Todd, “Emotional and Cognitive Changes During Adolescence,” Curr Opinion in Neurobiol 17 (2007): 251; B. Luna et al., “Maturation of Widely Distributed Brain Function Subserves Cognitive Development,” Neuroimage 13 (2001): 786; B. Schlaggar et al., “Functional Neuroanatomical Differences Between Adults and School-Age Children in the Processing of Single Words,” Sci 296 (2002): 1476.

  5.A. Wang et al., “Developmental Changes in the Neural Basis of Interpreting Communicative Intent,” SCAN 1 (2006): 107.

  6.T. Paus et al., “Maturation of White Matter in the Human Brain: A Review of Magnetic Resonance Studies,” Brain Res Bull 54 (2001): 255; A. Raznahan et al., “Patterns of Coordinated Anatomical Change in Human Cortical Development: A Longitudinal Neuroimaging Study of Maturational Coupling,” Neuron 72 (2011): 873; N. Strang et al., “Developmental Changes in Adolescents’ Neural Response to Challenge,” Developmental Cog Nsci 1 (2011): 560.

  7.C. Masten et al., “Neural Correlates of Social Exclusion During Adolescence: Understanding the Distress of Peer Rejection,” SCAN (2009): 143.

  8.J. Perrin et al., “Growth of White Matter in the Adolescent Brain: Role of Testosterone and Androgen Receptor,” J Nsci 28 (2008): 9519; T. Paus et al., “Sexual Dimorphism in the Adolescent Brain: Role of Testosterone and Androgen Receptor in Global and Local Volumes of Grey and White Matter,” Horm Behav 57 (2010): 63; A. Arnsten and R. Shansky, “Adolescence: Vulnerable Period for Stress-Induced PFC Function?” ANYAS 102 (2006): 143; W. Moore et al., “Facing Puberty: Associations Between Pubertal Development and Neural Responses to Affective Facial Displays,” SCAN 7 (2012): 35; R. Dahl, “Adolescent Brain Development: A Period of Vulnerabilities and Opportunities,” ANYAS 1021 (2004): 1