Emotion: Fear Circuitry

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Emotion Fear Circuitry

• Maygan Jorge

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Overview

• Neuroanatomy
• Fear Conditioning Sensory Pathways
• Neuroimaging Studies
• Neurotransmitters VCT
• Therapies

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Neuroanatomy

• Amygdala
• Hippocampus
• Medial Prefrontal Cortex
• Prefrontal Cortex
• Periaqueductal Gray

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Hippocampal Formation
Hypothalamus
Amygdala
http//www9.biostr.washington.edu/cgi-bin/DA/image
form
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Fear Conditioning Sensory Pathways
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Integrated Pathways
(Milan, M.J.)
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Auditory Pathway
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Conditioned Tone
http//www9.biostr.washington.edu/cgi-bin/DA/image
form
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Conditioned Tone
http//www9.biostr.washington.edu/cgi-bin/DA/image
form
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http//www9.biostr.washington.edu/cgi-bin/DA/image
form
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http//www9.biostr.washington.edu/cgi-bin/DA/image
form
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Olfactory Pathway
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Olfactory Bulb
Scent
http//www9.biostr.washington.edu/cgi-bin/DA/image
form
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Perirhinal Cortex
Input
http//www.mrc-cbu.cam.ac.uk/Common/Research/memor
y-knowledge/RD/RD.shtml
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Neuroimaging Studies Metanalysis of Emotion
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Limbic
0 10 20 30
40 50 60
Percentage of Studies
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Paralimbic
0 10 20 30
40 50 60
Percentage of Studies
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Uni/heteromodal
0 10 20 30
40 50 60
Percentage of Studies
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Other Areas
0 10 20 30
40 50 60
Percentage of Studies
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Neuroimaging Studies Metanalysis of Auditory,
Visual Stimuli and Cognitive Recall
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Limbic
0 10 20 30
40 50 60
Percentage of Studies
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Paralimbic
0 10 20 30 40
50 60
Percentage of Studies
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Uni/heteromodal
0 10 20 30
40 50 60
Percentage of Studies
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Other
0 10 20 30
40 50 60
Percentage of Studies
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Neurotransmitters

• GABA
• Benzodiazepines
• Monoamines (NA, DA, 5-HT)
• Histamine
• Acetylcholine
• Adenosine
• Cannabinoids
• Neuropeptides

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GABA

• Inhibits release of neurotransmitters involved in
  anxious states
• Suppresses both corticolimbic noradrenergic and
  serotinergic projections
• Post Synaptic to 5-HT and NA

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Benzodiazepines

• Enhances the affects of GABA
• Increasing the amplitude or duration at synapses

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Monoamines
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Noradrenaline

• Projections found in the hippocampus, amygdala,
  PAG, cortex, hypothalamus and all corticolimbic
  regions involved in integrating the response to
  anxiety
• Role in the Induction of Panic attacks

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Dopamine

• Comorbidity Schizophrenia, Depression,
  Parkinsons Disease and Drug Abuse.
• Amygdala in Parkinsons and electrophysiological
  Rat studies
• Prefrontal Cortex stress and fear
• Social Phobia suppression of transmission and
  receptors
• Conditioned Fear activation of VTA DA pathways
  to the amygdala and adjacent bed nucleus of the
  stria terminals.
• Receptors localized both pre and post
  synaptically to dopaminergic projections

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Serotonin

• Anxiolytic Effect (Antidepressants)
• Genetic Variation in humans of 5-HT reuptake
• Humans with low density 5-HT1A receptors more
  anxious than control (high levels)
• 5-HT1A agonists are anxiolytic

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Acetylcholine (Cholinergic Pathways)

• arousal and attention
• Hippocampus, amygdala, septum, PFC and other
  limbic regions
• Modulate activity of hypothalamo-corticotropic
  axis with monoaminergic, GABAergic and
  glutamergic pathways

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Adenosine

• A1 sites in hippocampus, septum and cortex
• Mice Lacking A1 demonstrated more anxiety
• Caffeine

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Cannabinoids

• CB1 receptors found in Cortex (entorhinal,
  cingulate, hippocampus, lateral septum, nucleus
  accumbens, amygdala and PAG
• Inhibit release of NA and DA
• Interfere with GABA in amygdala, hippocampus, PFC
  and other regions
• Relieve or induce anxiety in man
• CB1 receptor antagonists increase anxiety in
  rodents

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Neuropeptides

• Cholecystokinin (CCK)
• CCK1 hypothalamus, DRN, hippocampus and cortex
  (restricted)
• CCK2 throughout limbic system (receptor
  antagonists have anxiolytic effect in elevated
  plus maze studies but not Vogel Conflict Test)
• Both implicated in anxiogenic properties of CCK

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Corticotropin Releasing Factor

• Location Cortex, amygdala, hippocampus and
  hypothalamus
• Critical Role of CRF1 receptors in stress
  facilitate ACTH secretion from pituitary
• Blocked receptors diminish anxiety

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Vasopressin and Oxytocin

• Vasopressin released during stress
• Gene KO Vasopressin rats show low levels of
  anxiety (therefore anxiogenic)
• Little is known about oxytocin findings are
  controversial
• Oxytocin may play an opposite role (anxiolytic)

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NPY

• High levels found in nucleus accumbens, PAG,
  septum and amygdala
• More NPY is produced during habituation during
  stress
• Suggested that it acts as a buffer to LT exposure
  to anxiogenic stimuli
• Inhibits ACTH secretion

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Therapy

• Antidepressants
• SSRIs
• Mixed 5-HT/NA reuptake inhibitors (venlafaxine
  and duloxetine)
• Benzodiazepines
• NA reuptake inhibitors
• Virtual Reality

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Conclusion

• More fMRI and PET studies of activation comparing
  anxiety disorders to healthy subjects
• Research studying the integration of both
  neuroanatomy and neurochemistry in the brain
  taking the focus away from the amygdala
• Better understanding of the Visual pathway