Original Article

Neuropsychopharmacology (2017) 42, 895–903; doi:10.1038/npp.2016.238; published online 16 November 2016

β-Adrenergic Receptors Regulate the Acquisition and Consolidation Phases of Aversive Memory Formation Through Distinct, Temporally Regulated Signaling Pathways

Hillary C Schiff1, Joshua P Johansen2,3, Mian Hou1, David E A Bush1, Emily K Smith1, JoAnna E Klein1, Joseph E LeDoux1,4,5 and Robert M Sears1,5,6

  1. 1Center for Neural Science, New York University, New York, NY, USA
  2. 2RIKEN Brain Science Institute, Laboratory for Neural Circuitry of Memory, Wako-shi, Saitama, Japan
  3. 3Department of Life Sciences, Graduate School of Arts and Sciences, University of Tokyo, Tokyo, Japan
  4. 4Department of Psychology, New York University, New York, NY, USA
  5. 5Emotional Brain Institute, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA
  6. 6Department of Child and Adolescent Psychiatry, New York University School of Medicine, New York, NY, USA

Correspondence: Dr RM Sears, Center for Neural Science, New York University, 4 Washington Place, New York, NY 10003, USA, Tel: 212 998 3931, Fax: 212 995 4704, E-mail: robert.sears@nyu.edu

Received 25 January 2016; Revised 5 October 2016; Accepted 7 October 2016
Accepted article preview online 20 October 2016; Advance online publication 16 November 2016



Memory formation requires the temporal coordination of molecular events and cellular processes following a learned event. During Pavlovian threat (fear) conditioning (PTC), sensory and neuromodulatory inputs converge on post-synaptic neurons within the lateral nucleus of the amygdala (LA). By activating an intracellular cascade of signaling molecules, these G-protein-coupled neuromodulatory receptors are capable of recruiting a diverse profile of plasticity-related proteins. Here we report that norepinephrine, through its actions on β-adrenergic receptors (βARs), modulates aversive memory formation following PTC through two molecularly and temporally distinct signaling mechanisms. Specifically, using behavioral pharmacology and biochemistry in adult rats, we determined that βAR activity during, but not after PTC training initiates the activation of two plasticity-related targets: AMPA receptors (AMPARs) for memory acquisition and short-term memory and extracellular regulated kinase (ERK) for consolidating the learned association into a long-term memory. These findings reveal that βAR activity during, but not following PTC sets in motion cascading molecular events for the acquisition (AMPARs) and subsequent consolidation (ERK) of learned associations.

Extra navigation