Brain Structure and Function

, Volume 221, Issue 5, pp 2401–2426 | Cite as

Stress, trauma and PTSD: translational insights into the core synaptic circuitry and its modulation

  • Maxwell R. BennettEmail author
  • Sean N. Hatton
  • Jim Lagopoulos


Evidence is considered as to whether behavioral criteria for diagnosis of post-traumatic stress disorder (PTSD) are applicable to that of traumatized animals and whether the phenomena of acquisition, extinction and reactivation of fear behavior in animals are also successfully applicable to humans. This evidence suggests an affirmative answer in both cases. Furthermore, the deficits in gray matter found in PTSD, determined with magnetic resonance imaging, are also observed in traumatized animals, lending neuropsychological support to the use of animals to probe what has gone awry in PTSD. Such animal experiments indicate that the core synaptic circuitry mediating behavior following trauma consists of the amygdala, ventral-medial prefrontal cortex and hippocampus, all of which are modulated by the basal ganglia. It is not clear if this is the case in PTSD as the observations using fMRI are equivocal and open to technical objections. Nevertheless, the effects of the basal ganglia in controlling glutamatergic synaptic transmission through dopaminergic and serotonergic synaptic mechanisms in the core synaptic circuitry provides a ready explanation for why modifying these mechanisms delays extinction in animal models and predisposes towards PTSD. In addition, changes of brain-derived neurotrophic factor (BDNF) in the core synaptic circuitry have significant effects on acquisition and extinction in animal experiments with single nucleotide polymorphisms in the BDNF gene predisposing to PTSD.


Stress PTSD 



Anterior cingulate cortex


Basal amygdala


Brain-derived neurotrophic factor


Basolateral amygdala


Bed nucleus of the stria terminalis


Central amygdala


Central lateral amygdala


Central medial amygdala


Cortical metabolic rate of oxidized glucose


Conditioned response


Conditioned stimulus


Dorsolateral periaqueductal gray


Diagnostic and statistical manual of mental disorders


Diffusion tensor imaging


Extinction neurons


Fear neurons


Fractional anisotropy


Globus pallidus




Inhibitory intercalated region of amygdala


Dorsal inhibitory intercalated region of amygdala


Ventral inhibitory intercalated region of amygdala


Dorsal lateral nucleus


Lateral hypothalamus


Mid-cingulate cortex


Medial prefrontal cortex


Messenger RNA


Magnetic resonance imaging


Nucleus accumbens




Orbitofrontal cortex


Peribrachial nuclei


Periaqueductal gray


Positron emission tomography




Post-traumatic stress disorder


Paraventricular nucleus


Rostral anterior cingulate cortex


Regional cerebral blood flow


Retrosplenal cortex


Substantia nigra pars reticulate


Single nucleotide polymorphisms


Neurotrophic tyrosine kinase receptor, type 2


Unconditioned stimulus


Ventral periaqueductal gray


Ventral-medial prefrontal cortex


Ventral tegmental area


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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Maxwell R. Bennett
    • 1
    Email author
  • Sean N. Hatton
    • 1
  • Jim Lagopoulos
    • 1
  1. 1.Neuropsychiatry Research Unit, Brain and Mind Research InstituteUniversity of SydneyCamperdownAustralia

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