Glucocorticoid receptors recruit the CaMKIIα-BDNF-CREB pathways to mediate memory consolidation

Nat Neurosci. 2012 Dec;15(12):1707-14. doi: 10.1038/nn.3266. Epub 2012 Nov 18.


Emotionally important events are well remembered. Although memories of emotional experiences are known to be mediated and modulated by stress hormones such as glucocorticoids, little is known about the underlying molecular mechanisms. We found that the hippocampal glucocorticoid receptors that are critically engaged during the formation of long-term inhibitory avoidance memory in rats were coupled to the activation of CaMKIIα, TrkB, ERK, Akt, PLCγ and CREB, as well as a to a substantial induction of Arc and synaptic GluA1. Most of these changes, which are initiated by a nongenomic effect of glucocorticoid receptors, were also downstream of the activation of brain-derived neurotrophic factor (BDNF). Hippocampal administration of BDNF, but not of other neurotrophins, selectively rescued both the amnesia and the molecular impairments produced by glucocorticoid receptor inhibition. Thus, glucocorticoid receptors mediate long-term memory formation by recruiting the CaMKIIα-BDNF-CREB-dependent neural plasticity pathways.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Avoidance Learning / physiology
  • Brain-Derived Neurotrophic Factor / physiology*
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / physiology*
  • Cyclic AMP Response Element-Binding Protein / physiology*
  • Male
  • Memory, Long-Term / physiology*
  • Protein Transport / physiology
  • Rats
  • Rats, Long-Evans
  • Receptors, AMPA / physiology*


  • Brain-Derived Neurotrophic Factor
  • Cyclic AMP Response Element-Binding Protein
  • Receptors, AMPA
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • glutamate receptor ionotropic, AMPA 1