AUTHOR=Huang Bing , Zhu Huiwen , Zhou Yiming , Liu Xing , Ma Lan 
  
TITLE=Unconditioned- and Conditioned- Stimuli Induce Differential Memory Reconsolidation and β-AR-Dependent CREB Activation
  
JOURNAL=Frontiers in Neural Circuits
  
VOLUME=Volume 11 - 2017
  
YEAR=2017
  
URL=https://www.frontiersin.org/journals/neural-circuits/articles/10.3389/fncir.2017.00053
  
DOI=10.3389/fncir.2017.00053
  
ISSN=1662-5110
  
ABSTRACT=Consolidated long-term fear memories become labile and reconsolidated upon retrieval by the presentation of conditioned stimulus (CS) or unconditioned stimulus (US). Whether CS-retrieval or US-retrieval will trigger different memory reconsolidation processes is unknown. In this study, we introduced a sequential fear conditioning paradigm that Footshock was paired with two distinct Sounds. Propranolol, β-adrenergic receptor (β-AR) antagonist, treated after US-retrieval impaired freezing behavior evoked by CS-A and CS-B. Betaxolol, a selective β1-AR antagonist, showed the similar effects as propranolol. However, propranolol treatment after CS-retrieval only inhibited freezing behavior evoked by the same CS, i.e., CS-A (or CS-B), not the other CS. These data suggest that β-AR is critically involved in US-retrieval triggered memory reconsolidation of fear conditioning as CS-retrieval, and β-AR blockade after US-retrieval disrupts more CS-US associations than CS-retrieval does. Furthermore, US-retrieval induced significant CREB activation in almost the whole amygdala and hippocampus, but CS-retrieval only stimulated CREB activation in the lateral amygdala (LA) and CA3. In addition, propranolol treatment suppressed CREB activation by memory retrieval. These data indicate that US-retrieval triggers more memory traces activation than CS-retrieval does, leading to memory reconsolidation of more CS-US associations.