Enhanced noradrenergic activity potentiates fear memory consolidation and reconsolidation by differentially recruiting α1- and β-adrenergic receptors

Abstract

Consolidation and reconsolidation are phases of memory stabilization that diverge slightly. Noradrenaline is known to influence both processes, but the relative contribution of a1-and b-adrenoceptors is unclear. The present study sought to investigate this matter by comparing their recruitment to consolidate and/or reconsolidate a contextual fear memory trace under enhanced noradrenergic activity induced by yohimbine. We report that this a2-adrenoceptor antagonist was able to potentiate fear memory trace consolidation or reconsolidation when administered immediately after acquisition or retrieval, respectively, resulting in increased freezing expression. In either case, generalization of this response to an unpaired context was also seen when it achieved a ceiling level in the paired context. These effects endured for over 7 d and relied on action at central rather than peripheral sites, but were prevented when a memory trace was not acquired, when memory reactivation was omitted, or when administration of yohimbine was delayed until 6 h after acquiring or retrieving the memory trace. The b-adrenoceptor antagonist propranolol was able to prevent the above-mentioned effects of yohimbine, while pretreatment with the a1-adrenoceptor antagonist prazosin blocked only its facilitating effects on memory reconsolidation. These results highlight a differential participation of a1-and b-adrenoceptors in fear memory processing. Moreover, it was shown that the a2-adrenoceptor agonist clonidine, as opposed to yohimbine, mitigates fear expression by weakening memory consolidation or reconsolidation.

β-Arrestin–biased signaling mediates memory reconsolidation

“…Studies have shown that blocking β-adrenergic transmission by propranolol impairs memory reconsolidation in auditory fear conditioning, spatial radial maze, and cocaine-induced CPP (12,(26)(27)(28)(29)(30); inhibition of basal and stimulated activities of certain components of G protein-coupled pathways associated with neuroplasticity, such as PKA, ERK, and CREB, disrupts reconsolidation of fear and object recognition memories (31)(32)(33)(34). In cocaine-associated reward memory task, bilateral intraamygdalar infusions of the PKA inhibitor Rp-cAMPS following light/tone stimulus reactivation decreases subsequent cue-induced reward memory reconsolidation (35).…”

“…In therapeutic contexts, disrupting the process of reconsolidation could change or erase pathophysiological memories (28,30,38). Blockade of β-AR signaling disrupts reconsolidation of memory for learned behaviors.…”

Peripheral and central CB1 cannabinoid receptors control stress-induced impairment of memory consolidation

“…Moreover, stress-induced activation of the HPA axis involves the synthesis and secretion of glucocorticoids (cortisol in humans and corticosterone in most rodents) from the adrenal cortex (8). Both animal and human studies have shown that these stress hormones have profound effects on cognition by acting on specific brain regions involved in the processing of emotional stimuli (1,(9)(10)(11)(12).…”

Adverse Outcome Pathway on binding of agonists to ionotropic glutamate receptors in adult brain leading to excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment

“…Noradrenaline is associated with memory processing as it induces lasting changes in the brain that could sustain memories over time (Gazarini et al, 2013). As confirmed later on its neurotransmission indeed strengthens memory-related synaptic plasticity such as long-term potentiation, allowing memories to be formed and maintained in a more intense and enduring manner, a notion particularly valid for those with emotional content (Joëls et al, 2011).…”

“…Like other types of memory, an emotional memory has to be consolidated to allow its later retrieval. Accumulating evidence has indicated that noradrenaline acts during these gradual stages to finetune the strength and/or persistence of a memory (Guzmán-Ramos, 2012; Gazarini et al, 2013).…”