2017-03-21 09:01:51

Don't You Worry 'Bout a Thing

Today's topics

  • Fear
  • Stress

Inducing "fear-like" behavior in animals

http://www.cns.nyu.edu/labs/ledouxlab/images/image_research/fear_conditioning.jpg

Rat vs. Human

Adapted from (Davis 1992)

Your thoughts: Can we use an animal model to study 'emotion'?

Amygdala circuits

(Medina et al. 2002)

Amygdala's inputs

  • Convergent inputs
    • Thalamus
    • Cerebral cortex

Amygdala's outputs

  • Project to
    • CG (central gray matter) of tegmentum: behavior
    • LH (lateral hyp): ANS
    • PVN (paraventricular n. of hyp): hormones
  • Fast-acting, involuntary responses
  • Lesions of amygdala impair 'fear conditioning'

Cerebral cortex role

  • Response discrimination?
    • Cortex lesions cause generalized not cue-specific fear response
  • Fast, crude responses vs. slower, detailed ones
    • That’s a stick, not a snake!
    • Prefrontal cortex and response inhibition

But, are we really studying learned 'fear'?

  • Amygdala connected to other 'affective' nodes in neural network
  • Emotion not just about subjective feelings

Amygdala as processing hub

(Pessoa 2008)

Amygdala as key hub in circuit for survival

(J. LeDoux 2012)

Emotion as global physiological/behavioral "state"

(J. LeDoux 2012)

"Emotional" stimuli serve multiple roles

(J. LeDoux 2012)

Stress

Stressors linked with biological imperatives

  • Sustenance
    • Hunger, thirst
  • Well-being/defense
    • Threat

Stressors linked with biological imperatives

  • Reproduction
    • Rejection
  • Affiliation
    • Loneliness

Stress and the brain

(McEwen 2007)

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 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

Glucocorticoid cascade hypothesis

  • Cort receptors in hippocampus, amygdala, hypothalamus
    • Hippocampus regulates HPA axis via hypothalamus
  • Prolonged cortisol exposure reduces hippocampus response
    • Reduces volume, connectivity in hippocampus
  • Hip critical for long-term memory formation
    • Chronic stress impairs long-term memory

But, cortisol -> stress link not straightforward

(Å. Faresjö et al. 2013)

Stress and coping across the animal kingdom

  • Pain thresholds lower (sensitivity greater) when a mouse's cage mate is also in pain
  • Rats will cooperate to release distressed cage mage, foregoing food rewards
  • (Sapolsky 2016)

Why Zebras Don't Get Ulcers

Your stress ain't like mine

  • Phasic (short-term) vs. Chronic (long-term)
  • Physical stress (hunger, thirst, injury, disease) vs. social stress

Main points

  • Biological approach to emotion
    • Behavior
    • Physiological states
    • Subjective feelings
    • Adaptive function
  • Networks of brain systems, multiple NT systems

References

Davis, Michael. 1992. “The Role of the Amygdala in Fear-Potentiated Startle: Implications for Animal Models of Anxiety.” Trends in Pharmacological Sciences 13. Elsevier: 35–41. doi:10.1016/0165-6147(92)90014-W.

Faresjö, Åshild, Elvar Theodorsson, Marios Chatziarzenis, Vasiliki Sapouna, Hans-Peter Claesson, Jenny Koppner, and Tomas Faresjö. 2013. “Higher Perceived Stress but Lower Cortisol Levels Found Among Young Greek Adults Living in a Stressful Social Environment in Comparison with Swedish Young Adults.” PLoS ONE 8 (9): e73828. doi:10.1371/journal.pone.0073828.

LeDoux, Joseph. 2012. “Rethinking the Emotional Brain.” Neuron 73 (4): 653–76. doi:10.1016/j.neuron.2012.02.004.

McEwen, B. S. 2007. “Physiology and Neurobiology of Stress and Adaptation: Central Role of the Brain.” Physiological Reviews 87 (3): 873–904. doi:10.1152/physrev.00041.2006.

Medina, Javier F, J Christopher Repa, Michael D Mauk, and Joseph E LeDoux. 2002. “Parallels Between Cerebellum-and Amygdala-Dependent Conditioning.” Nature Reviews Neuroscience 3 (2). Nature Publishing Group: 122–31. doi:10.1038/nrn728.

Pessoa, Luiz. 2008. “On the Relationship Between Emotion and Cognition.” Nature Reviews Neuroscience 9 (2): 148–58. doi:10.1038/nrn2317.

Sapolsky, Robert M. 2016. “Psychiatric Distress in Animals Versus Animal Models of Psychiatric Distress.” Nature Neuroscience 19 (11): 1387–9. doi:10.1038/nn.4397.