AMPA receptor exchange underlies transient memory destabilization on retrieval

Abstract

The authors note, "For the 'hybrid' location discrimination task, we report data obtained from 27 electrodes, 16 of which were in area 1; the 11 electrodes in area 3b were divided evenly across the two animals (6 and 5). We had previously tested all of the electrodes, including those in area 3b, in the detection and discrimination tasks (as shown in Fig. 3) and found them all to yield approximately equivalent performance (see Fig 3A). We noticed in the hybrid location discrimination task, however, that one of the animals performed much more poorly based on stimulation of area 3b than it did based on stimulation of area 1 (while the other animal performed better based on stimulation of area 1). Having no reason to question any of the arrays, we attributed this discrepancy to differences across animals and arrived at the conclusion, based on pooled data from both animals, that stimulation of the two areas yields equivalent performance in the 'hybrid location discrimination' task. The overall conclusion, then, was that stimulation of neurons in area 3b and 1 evokes percepts that are equally localized on the skin."Shortly after publication of the paper, we repeated detection experiments across the arrays and found that the animal could no longer detect stimulation through the array in area 3b that had yielded poor performance in the hybrid location discrimination task. It is therefore likely that this array had failed between the time we conducted the initial detection and discrimination experiments and the time we conducted the hybrid location discrimination task (which required 2-3 months of retraining). If this is the case, and we eliminate data from that bad array, then the median performance on hybrid trials is 83% (up from the 80% that was originally reported), which is still statistically poorer than that on the location-matched mechanical trials [median difference between performance on mechanical and hybrid trials was 3.3% rather than 5.6%, t (119) = 6.1, P < 0.001] (see the corrected Fig. 2). Thus, we probably underestimated overall performance on hybrid trials, and thus the degree to which artificial percepts are localized, in the original publication. Importantly, however, performance on hybrid trials based on stimulation of area 3b was significantly better than performance based on stimulation of area 1 [median Δp = 0.028 and 0.054 for areas 3b and 1, respectively; t test: t (76) = 2.8, P < 0.01]. Thus, based on the data obtained from only one animal, it seems as though stimulation of area 3b elicits more localized percepts than does stimulation of area 1, as might be expected given that neurons in area 3b tend to have smaller receptive fields than their counterparts in area 1 (1, 2)."As a result of this error, Fig. 2 and its legend appeared incorrectly. The corrected figure and its corresponding legend appear below. On both mechanical and hybrid trials, the relative locations of stimuli applied to widely spaced digits were more accurately discriminated than were the relative locations of stimuli applie...

Cholinergic manipulations bidirectionally regulate object memory destabilization

“…An important topic for future investigation regards the intracellular mechanisms involved in ACh-induced memory destabilization. Activation of M1 muscarinic receptors can increase post-synaptic insertion of AMPA receptors (Fernández de Sevilla et al 2008), providing a potential mechanistic connection between the effects of cholinergic transmission on object memory destabilization and the demonstrated requirement of AMPA receptor exchange for fear memory destabilization (Hong et al 2013). Questions for future research concern whether a similar process occurs within PRh for object memories and the nature of muscarinic receptor subtype involvement in the effects demonstrated here.…”

“…Recently, a better understanding of the neural mechanisms underlying memory destabilization-i.e., the return of memories to a labile state after reactivation-has begun to take shape (Ben Mamou et al 2006;Lee et al 2008;Suzuki et al 2008;Choi et al 2010;Hong et al 2013;Milton et al 2013). For example, degradation of synaptic proteins via ubiquitin proteasome system (UPS) activation likely underlies the putative synaptic uncoupling of the memory trace that could enable various forms of potential memory modification during the destabilization period (e.g., erasure or weakening, updating, strengthening) (Lee 2008;Lee et al 2008;Choi et al 2010).…”

Calcineurin inhibition blocks within-, but not between-session fear extinction in mice

“…Interestingly, all three of these molecules seem to be specifically involved in extinction, but not in the initial acquisition of fear conditioning (Cain et al 2002;Marsicano et al 2002;Baumgärtel et al 2008;Havekes et al 2008). The three of them have also been reported to be required for memory destabilization during reconsolidation (Suzuki et al 2008;Kim et al 2011;De Oliveira Alvares et al 2013;Fukushima et al 2014), along with other mechanisms such as AMPA receptor endocytosis (Hong et al 2013) and protein degradation through the ubiquitin-proteasome system (Lee 2008;Lee et al 2008;Sol Fustiñana et al 2014). This is in line with the view that these molecular components could be part of a system involved in the labilization of synaptic plasticity established by consolidation of the original memory trace (Almeida-Corrêa and Amaral 2014).…”

“…targets have also been implicated in memory destabilization during reconsolidation Hong et al 2013) and in extinction (Kim et al 2007;Dalton et al 2008;Lee et al 2008), suggesting that this memory labilization system might mediate both the labilization component of reconsolidation and the within-session component of memory extinction.…”

Reconsolidation and the Dynamic Nature of Memory

“…Learning is thought to lead to AMPA receptor trafficking: calcium-permeable AMPA receptors are inserted into the postsynaptic density (PSD), then over time replaced by calcium-impermeable receptors (Rumpel et al 2005). Hong et al (2013) asked what the AMPA receptor dynamics would be when a memory is destabilized and then reconsolidated. They found that memory destabilization is associated with calcium-permeable AMPA receptors.…”