Exposure to Uncontrollable Stress Impairs PFC Function

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Exposure to even mild, uncontrollable stress causes a rapid loss of PFC function. Feedforward Ca2+-PKC and cAMP-PKA  signaling rapidly opens K+ channels to disconnect dlPFC networks and reduce neuronal firing, i.e. Going To Hell In A Handbasket.


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 However, there are mechanisms that inhibit these stress reactions and restore PFC top-down control. Importantly, many of these restorative mechanisms are the target of genetic insults in mental illness.

If you are interested:

  • Arnsten (2009) Stress signalling pathways that impair prefrontal cortex structure and function. Nat Rev Neurosci. 10: 410-22.
  • Birnbaum et al. (2004) Protein kinase C overactivity impairs prefrontal cortical regulation of working memory. Science 306: 882-4.


Acute Stress Rapidly takes PFC Offline to Switch Control to more Primitive Circuits

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When we are alert and feel in control, there are moderate amounts of release of neuromodulators such as norepinephrine and dopamine which optimize PFC top-down control. However, when we feel stressed and out of control, high levels of norepinephrine and dopamine release rapidly weaken PFC, while strengthening more primitive emotional responses and habits mediated by the amygdala and striatum. This can save our lives when we are in danger and rapid, reflexive responding is needed, but can be detrimental when more thoughtful solutions are needed.