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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
Review

Abstract

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.

Keywords

Stress PTSD 

Abbreviations

ACC

Anterior cingulate cortex

BA

Basal amygdala

BDNF

Brain-derived neurotrophic factor

BLA

Basolateral amygdala

BNST

Bed nucleus of the stria terminalis

CEA

Central amygdala

CEl

Central lateral amygdala

CEm

Central medial amygdala

CMRglc(ox)

Cortical metabolic rate of oxidized glucose

CR

Conditioned response

CS

Conditioned stimulus

dlPAG

Dorsolateral periaqueductal gray

DSM

Diagnostic and statistical manual of mental disorders

DTI

Diffusion tensor imaging

E

Extinction neurons

F

Fear neurons

FA

Fractional anisotropy

GPA

Globus pallidus

IL

Infralimbic

ITC

Inhibitory intercalated region of amygdala

ITCd

Dorsal inhibitory intercalated region of amygdala

ITCv

Ventral inhibitory intercalated region of amygdala

LAd

Dorsal lateral nucleus

LH

Lateral hypothalamus

MCC

Mid-cingulate cortex

mPFC

Medial prefrontal cortex

mRNA

Messenger RNA

MRI

Magnetic resonance imaging

NAc

Nucleus accumbens

NMDA

N-methyl-d-aspartate

OFC

Orbitofrontal cortex

PB

Peribrachial nuclei

PAG

Periaqueductal gray

PET

Positron emission tomography

PL

Prelimbic

PTSD

Post-traumatic stress disorder

PVN

Paraventricular nucleus

rACC

Rostral anterior cingulate cortex

rCBF

Regional cerebral blood flow

RSG

Retrosplenal cortex

SNr

Substantia nigra pars reticulate

SNPs

Single nucleotide polymorphisms

TrkB

Neurotrophic tyrosine kinase receptor, type 2

US

Unconditioned stimulus

vPAG

Ventral periaqueductal gray

vmPFC

Ventral-medial prefrontal cortex

VTA

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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