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Learn Mem. 2017 Aug 16;24(9):432-439. doi: 10.1101/lm.044412.116. Print 2017 Sep.

Characterization of the amplificatory effect of norepinephrine in the acquisition of Pavlovian threat associations.

Author information

Center for Neural Science, New York University, New York, New York 10003, USA.
Emotional Brain Institute, Nathan Kline Institute for Psychiatric Research, Orangeburg, New York 10962, USA.
Department of Neurobiology and Behavior, The State University of New York-Stony Brook, Stony Brook, New York 11794, USA.


The creation of auditory threat Pavlovian memory requires an initial learning stage in which a neutral conditioned stimulus (CS), such as a tone, is paired with an aversive one (US), such as a shock. In this phase, the CS acquires the capacity of predicting the occurrence of the US and therefore elicits conditioned defense responses. Norepinephrine (NE), through β-adrenergic receptors in the amygdala, enhances threat memory by facilitating the acquisition of the CS-US association, but the nature of this effect has not been described. Here we show that NE release, induced by the footshock of the first conditioning trial, promotes the subsequent enhancement of learning. Consequently, blocking NE transmission disrupts multitrial but not one-trial conditioning. We further found that increasing the time between the conditioning trials eliminates the amplificatory effect of NE. Similarly, an unsignaled footshock delivered in a separate context immediately before conditioning can enhance learning. These results help define the conditions under which NE should and should not be expected to alter threat processing and fill an important gap in the understanding of the neural processes relevant to the pathophysiology of stress and anxiety disorders.

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