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 in which footshock (FS) was paired with two distinct sounds (CS-A and CS-B). The treatment with propranolol, a β-adrenergic receptor (β-AR) antagonist, after US (FS)-retrieval impaired freezing behavior evoked by either CS-A or CS-B. Betaxolol, a selective β1-AR antagonist, showed similar effects. However, propranolol treatment after retrieval by one CS (e.g., CS-A) only inhibited freezing behavior evoked by the same CS (i.e., CS-A), not the other CS (CS-B). These data suggest that β-AR is critically involved in reconsolidation of fear memory triggered by US- and CS-retrieval, whereas β-AR blockade after US-retrieval disrupts more CS-US associations than CS-retrieval does. Furthermore, significant CREB activation in almost the whole amygdala and hippocampus was observed after US-retrieval, but CS-retrieval only stimulated CREB activation in the lateral amygdala and the CA3 of hippocampus. In addition, propranolol treatment suppressed memory retrieval-induced CREB activation. These data indicate that US-retrieval activates more memory traces than CS-retrieval does, leading to memory reconsolidation of more CS-US associations.
Highlights
In Pavlovian threat conditioning, an initially neutral conditioned stimulus (CS), such as a tone, is paired with an aversive unconditioned stimulus (US), typically an electric shock, which evokes pain or strong somatic discomfort (Maren, 2001b; Nader and Hardt, 2009)
The present results showed that administration of β-adrenergic receptor (β-AR) antagonism after US-retrieval disrupted fear memory reconsolidation in response to both CS, while β-AR blockade after CS-retrieval only selectively impaired fear memory reconsolidation evoked by the same CS
Recent study has shown that two fear-conditioning events that occur within 6 h are coallocated to overlapping populations of neurons in the LA, and extinction of event2 memory by presenting CS2 decreases the fear memory related to CS1, indicating that memories links when occur closely (Rashid et al, 2016)
Summary
In Pavlovian threat (fear) conditioning, an initially neutral conditioned stimulus (CS), such as a tone, is paired with an aversive unconditioned stimulus (US), typically an electric shock, which evokes pain or strong somatic discomfort (Maren, 2001b; Nader and Hardt, 2009). Recent studies reported that US presentation alone after fear memory consolidation induced a reconsolidation process which, when disrupted by protein synthesis inhibitor, results in a decrease in CS-evoked behavioral fear memory in an amygdaladependent manner (Debiec et al, 2010; Díaz-Mataix et al, 2011). Converging evidence using rodents and human subjects reveals that noradrenergic signaling is critically involved in CS-retrieval induced memory reconsolidation of fear conditioning. Systemic or intra-LA injection of β-AR antagonist after retrieval reduces fear memory in rats (Debiec and Ledoux, 2004; Muravieva and Alberini, 2010); disruption of noradrenergic signaling during reconsolidation process reduces long-term emotional memory in healthy humans (Lonergan et al, 2013; Kroes et al, 2014). Whether β-AR dependent signaling involved in US triggered memory reconsolidation is unknown We addressed these issues by using a sequential conditioning including two different sounds associated with footshock (FS) in the training session. Our data revealed that β-adrenergic signaling mediates US triggered memory reconsolidation of fear conditioning, and US-retrieval might activate more memory traces than CS-retrieval does
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