Brain Structure and Function

, Volume 223, Issue 4, pp 1731–1745 | Cite as

Repeated shock stress facilitates basolateral amygdala synaptic plasticity through decreased cAMP-specific phosphodiesterase type IV (PDE4) expression

  • Steve Ryan
  • Chenchen Li
  • Aurélie Menigoz
  • Rimi Hazra
  • Joanna Dabrowska
  • David Ehrlich
  • Katelyn Gordon
  • Donald G. Rainnie
Original Article


Previous studies have shown that exposure to stressful events can enhance fear memory and anxiety-like behavior as well as increase synaptic plasticity in the rat basolateral amygdala (BLA). We have evidence that repeated unpredictable shock stress (USS) elicits a long-lasting increase in anxiety-like behavior in rats, but the cellular mechanisms mediating this response remain unclear. Evidence from recent morphological studies suggests that alterations in the dendritic arbor or spine density of BLA principal neurons may underlie stress-induced anxiety behavior. Recently, we have shown that the induction of long-term potentiation (LTP) in BLA principal neurons is dependent on activation of postsynaptic D1 dopamine receptors and the subsequent activation of the cyclic adenosine 5′-monophosphate (cAMP)—protein kinase A (PKA) signaling cascade. Here, we have used in vitro whole-cell patch-clamp recording from BLA principal neurons to investigate the long-term consequences of USS on their morphological properties and synaptic plasticity. We provided evidence that the enhanced anxiety-like behavior in response to USS was not associated with any significant change in the morphological properties of BLA principal neurons, but was associated with a changed frequency dependence of synaptic plasticity, lowered LTP induction threshold, and reduced expression of phosphodiesterase type 4 enzymes (PDE4s). Furthermore, pharmacological inhibition of PDE4 activity with rolipram mimics the effects of chronic stress on LTP induction threshold and baseline startle. Our results provide the first evidence that stress both enhances anxiety-like behavior and facilitates synaptic plasticity in the amygdala through a common mechanism of PDE4-mediated disinhibition of cAMP-PKA signaling.


Macromolecular complexes Compartmentalization a-Kinase anchoring protein Basolateral amygdala Chronic stress Morphology 


Compliance with ethical standards


This work was supported by funding from the National Institute of Mental Health, Grant MH069852 to DGR.


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Authors and Affiliations

  1. 1.Behavioral Neuroscience and Psychiatric DisordersYerkes National Primate Research CenterAtlantaUSA
  2. 2.Department of PsychiatryEmory University School of MedicineAtlantaUSA
  3. 3.Department of Medicine, Center for Translational and International Hematology, Vascular Medicine InstituteUniversity of PittsburghPittsburghUSA
  4. 4.Department of Cellular and Molecular Pharmacology, Chicago Medical SchoolRosalind Franklin University of Medicine and ScienceNorth ChicagoUSA
  5. 5.Department of Neuroscience, Chicago Medical SchoolRosalind Franklin University of Medicine and ScienceNorth ChicagoUSA
  6. 6.Department of Neuroscience and Physiology, Neuroscience InstituteNYU Langone Medical CenterNew YorkUSA
  7. 7.Department of OtolaryngologyNYU Langone School of MedicineNew YorkUSA

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