Retrieval is not necessary to trigger reconsolidation of object recognition memory in the perirhinal cortex

Abstract

Memory retrieval has been considered as requisite to initiate memory reconsolidation; however, some studies indicate that blocking retrieval does not prevent memory from undergoing reconsolidation. Since N-methyl-D-aspartate (NMDA) and aamino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors in the perirhinal cortex have been involved in object recognition memory formation, the present study evaluated whether retrieval and reconsolidation are independent processes by manipulating these glutamate receptors. The results showed that AMPA receptor antagonist infusions in the perirhinal cortex blocked retrieval, but did not affect memory reconsolidation, although NMDA receptor antagonist infusions disrupted reconsolidation even if retrieval was blocked. Importantly, neither of these antagonists disrupted short-term memory. These data suggest that memory underwent reconsolidation even in the absence of retrieval.Retrieval has been held as an indispensable condition to trigger memory reconsolidation (Nader et al. 2000;Dudai 2006). However, recent reports showed that inhibition of retrieval does not disrupt memory reconsolidation in several memory paradigms (Ben Mamou et al. 2006;Rodriguez-Ortiz et al. 2012;Balderas et al. 2013;Barreiro et al. 2013;Milton et al. 2013;Garcia-Delatorre et al. 2014). Some of these studies have shown that inhibition of the a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors of the basolateral amygdala impairs retrieval of aversive memories, without affecting its reconsolidation (Ben Mamou et al. 2006;Rodriguez-Ortiz et al. 2012;Milton et al. 2013; GarciaDelatorre et al. 2014). Conversely, inhibition of N-methyl-Daspartate (NMDA) receptors disrupts reconsolidation of aversive memories but spare retrieval (Garcia-Delatorre et al. 2014).A recent study evaluated the capacity of retrieval to trigger memory reconsolidation in a nonaversive task, i.e., the object recognition task (Balderas et al. 2013). The object recognition task is widely used to evaluate recognition memory in rodents, since it has been suggested that it maintains a close analogy to the recognition memory task used in humans to assess impairments in declarative memories (Reed and Squire 1997). In this regard, muscimol (GABA A receptor agonist) infusions in the perirhinal cortex blocked retrieval, but this effect did not impede memory to undergo reconsolidation in a protocol of memory updating, suggesting that retrieval and reconsolidation of object recognition memory (ORM) are independent processes (Balderas et al. 2013).It has been reported that glutamate receptor activity in the perirhinal cortex has an important and dissociative role mediating synaptic transmission in several stages of ORM. In one study, it was showed that the AMPA receptor antagonist 6-cyano-7-nitroquinoxaline (CNQX) impaired ORM retrieval when infused 15 min before, since rats did not show preference for the new object. On the other hand, the group infused 15 min before reactivation with the NMDA receptor antagonist A...

Extinction learning, which consists of the inhibition of retrieval, can be learned without retrieval

“…Thus, perception of the CS seems to be far more important for the triggering of extinction learning than the behavioral response to it. Unless some other subbehavioral correlate of retrieval is found, this seems to be the simplest and most parsimonious explanation for the present results and perhaps also for those of Balderas et al When our results are put together with those obtained by Bermudez-Rattoni and his group in two other different tasks (5,6,16,21), it seems clear that extinction and reconsolidation must be considered under a new light: perhaps not as opposite behavioral processes that can be triggered by retrieval (14) but possibly as part of a continuum or a diversity of protein synthesismediated events, some of which may indeed overlap (31), and that can be set into motion by the simple perception of the CS or CSs, or some other event other than the performance or the inhibition of performance of a behavioral response.…”

“…In both tasks, the drugs selectively blocked retrieval but spared reconsolidation, suggesting that the two neural processes are independent from each other (16,21). In contrast, a glutamate NMDA receptor antagonist blocked the reconsolidation of conditioned taste aversion when given into the BLA (21) and that of object recognition when infused into the perirhinal cortex (16).…”

“…Reconsolidation is viewed as a consequence of the labilization of consolidated memories at the time of the unreinforced retrieval, which renders them open to strengthening and updating (3)(4)(5)(6)(7)(14)(15)(16)(17)(18)(19)(20), whereas extinction is viewed as a form of learning to inhibit retrieval of original memory (8)(9)(10)(11)(12). Pavlov observed more than a century ago (8) that extinguished responses can recover spontaneously with the passage of time, which indicates that extinction does not erase memories.…”

“…Bermudez-Rattoni and his group showed that the performance of unreinforced retrieval is not necessary to trigger reconsolidation of conditioned taste aversion (5,21) or of object recognition learning (6,16). The methodology used by this group is very straightforward: it consists of the pharmacological blockade of retrieval with microinfusions of ciano-nitro-quinoxaline-dione, an antagonist of AMPA receptors (16,21), or of the GABA A receptor agonist muscimol (Mus) (5) given into the basolateral amygdala (BLA) for conditioned taste aversion or into the perirhinal cortex for object recognition (6).…”

“…The methodology used by this group is very straightforward: it consists of the pharmacological blockade of retrieval with microinfusions of ciano-nitro-quinoxaline-dione, an antagonist of AMPA receptors (16,21), or of the GABA A receptor agonist muscimol (Mus) (5) given into the basolateral amygdala (BLA) for conditioned taste aversion or into the perirhinal cortex for object recognition (6). In both tasks, the drugs selectively blocked retrieval but spared reconsolidation, suggesting that the two neural processes are independent from each other (16,21). In contrast, a glutamate NMDA receptor antagonist blocked the reconsolidation of conditioned taste aversion when given into the BLA (21) and that of object recognition when infused into the perirhinal cortex (16).…”