2018-11-02 11:17:31

Don't You Worry 'Bout a Thing

Today's topics

  • Fear
  • Stress
  • Reward

Animal model of learned 'fear'

Rat vs. Human

Amygdala circuits

Specificity of learning

  • Light/sound + footshock OR X-ray + saccharin vs
  • Light/sound + X-ray or footshock + saccharin

Circuitry

  • BLA, basolateral complex of the amygdala
  • CEA, central nucleus of the amygdala
  • ITC, intercalated cells of the amygdala
  • PL, prelimbic cortex
  • IL, infralimbic cortex
  • HPC, hippocampus
  • Thal, thalamus
  • PAG, periaqueductal gray
  • PBN, parabrachial nucleus

Brain under stress

  • Acute stress
    • Short duration
    • Fast action required
    • HPA (Cortisol), SAM (NE/Epi) axes
  • Brain detects threat
  • Mobilizes physiological, behavioral responses

Brain under stress

  • vs. Chronic or stress
    • Long duration, persistent

Glucocorticoids

  • Adrenal cortex releases hormones
    • Cortisol (hydrocortisone)
      • Increases blood glucose levels
      • Suppresses immune system
      • Reduces inflammation
      • Aids in metabolism
    • Receptors in brain and body

Cortisol and the brain

Impacts of acute stress

From cortisol to enhanced glutamate

Pleasure/reward

Neuroanatomy of 'happiness'

Rewards

  • A reward reinforces (makes more prevalent/probable) some behavior
  • Milner and Olds (Milner, 1989) discovered 'rewarding' power of electrical self-stimulation
  • (Heath, 1963) studied effects in human patients.

Electrical self-stimulation

"Reward" circuitry in the brain

Components of the "reward" circuit

  • Lateral Hypothalamus (Hyp)
  • Medial forebrain bundle (MFB)
  • Ventral tegmental area (VTA) in midbrain
  • Nucleus accumbens (nAcc)
  • Dorsal Raphe Nucleus/Locus Coeruleus (DR/LC)

Components of the "reward" circuit

  • Amygdala (Amy)
  • Hippocampus (HP)
  • Prefrontal cortex (PFC)

Nucleus accumbens and dorsal striatum

What does DA signal?

  • Hedonia and anhedonia
  • Incentive salience
  • Reward prediction error (RPE)

RPE

DA & GABA signaling in RPE

Expectation modulates DA signaling

DA network

Reward & Aversion Networks

Psychopharmacology of pleasure

  • Dopamine
  • Opioids
  • Cannabinoids
  • Serotonin, Norepinephrine
  • ACh

Endogenous morphine-like NTs (endorphins) from hyp, NST

Endogenous cannabinoid system

  • Cannabinoids, psychoactive compounds found in cannibis
  • Cannabinoid CB1 receptors in CNS; CB2 in body, immune system

Brain contains its own systems for binding drugs associated with 'pleasure'

  • Endogenous opioids (endorphins)
  • Endogenous cannabinoids

ACh projections in the CNS

(Cock, Vidailhet, & Arnulf, 2008)

References

Brandão, M. L., Zanoveli, J. M., Ruiz-Martinez, R. C., Oliveira, L. C., & Landeira-Fernandez, J. (2008). Different patterns of freezing behavior organized in the periaqueductal gray of rats: Association with different types of anxiety. Behavioural Brain Research, 188(1), 1–13. https://doi.org/10.1016/j.bbr.2007.10.018

Clapp, P., Bhave, S. V., & Hoffman, P. L. (n.d.). How Adaptation of the Brain to Alcohol Leads to Dependence. Retrieved from http://pubs.niaaa.nih.gov/publications/arh314/310-339.htm

Cock, V. C. D., Vidailhet, M., & Arnulf, I. (2008). Sleep disturbances in patients with parkinsonism. Nature Clinical Practice Neurology, 4(5), 254–266. https://doi.org/10.1038/ncpneuro0775

Davis, M. (1992). The role of the amygdala in fear-potentiated startle: Implications for animal models of anxiety. Trends in Pharmacological Sciences, 13, 35–41. https://doi.org/10.1016/0165-6147(92)90014-W

Flores, Á., Maldonado, R., & Berrendero, F. (2013). Cannabinoid-hypocretin cross-talk in the central nervous system: What we know so far. Neuropharmacology, 7, 256. https://doi.org/10.3389/fnins.2013.00256

Heath, R. G. (1963). Electrical self-stimulation of the brain in man. American Journal of Psychiatry, 120(6), 571–577. https://doi.org/10.1176/ajp.120.6.571

Kadmiel, M., & Cidlowski, J. A. (2013). Glucocorticoid receptor signaling in health and disease. Trends in Pharmacological Sciences, 34(9), 518–530. https://doi.org/10.1016/j.tips.2013.07.003

Kohls, G., Chevallier, C., Troiani, V., & Schultz, R. T. (2012). Social ‘wanting’dysfunction in autism: Neurobiological underpinnings and treatment implications. Journal of Neurodevelopmental Disorders, 4(10), 1–20. https://doi.org/10.1186/1866-1955-4-10

Kringelbach, M. L., & Berridge, K. C. (2009). Towards a functional neuroanatomy of pleasure and happiness. Trends in Cognitive Sciences, 13(11), 479–487.

Medina, J. F., Repa, J. C., Mauk, M. D., & LeDoux, J. E. (2002). Parallels between cerebellum-and amygdala-dependent conditioning. Nature Reviews Neuroscience, 3(2), 122–131. https://doi.org/10.1038/nrn728

Milner, P. M. (1989). The discovery of self-stimulation and other stories. Neuroscience & Biobehavioral Reviews, 13(2–3), 61–67. https://doi.org/10.1016/S0149-7634(89)80013-2

Musazzi, L., Tornese, P., Sala, N., & Popoli, M. (2017). Acute or chronic? A stressful question. Trends in Neurosciences. https://doi.org/10.1016/j.tins.2017.07.002

Nestler, E. J., & Carlezon, W. A. (2006). The mesolimbic dopamine reward circuit in depression. Biological Psychiatry, 59(12), 1151–1159. https://doi.org/10.1016/j.biopsych.2005.09.018

Pellman, B. A., & Kim, J. J. (2016). What can ethobehavioral studies tell us about the brain’s fear system? Trends in Neurosciences, 39(6), 420–431. https://doi.org/10.1016/j.tins.2016.04.001