NMDA GluN2A and GluN2B receptors play separate roles in the induction of LTP and LTD in the amygdala and in the acquisition and extinction of conditioned fear

Dalton, Gemma L.; Wu, Dong; Wang, Yu Tian; Floresco, Stan; Phillips, Anthony G.

doi:10.1016/j.neuropharm.2011.09.001

Cited by 125 publications

(125 citation statements)

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“…It has been shown consistently that GluA2 3Y does not impair the induction of LTP (see also Fig. 7) or other forms of hippocampal learning such as contextual fear conditioning (Ahmadian et al, 2004;Brebner et al, 2005;Dalton et al, 2008). Instead, GluA2 3Y blocks LTD, depotentiation (Fig.…”

Section: Discussionmentioning

confidence: 86%

“…Instead, GluA2 3Y blocks LTD, depotentiation (Fig. 7), reversal learning, and the acquisition of fear extinction memory, all of which critically involve the synaptic removal of GluA2/AMPARs (Dalton et al, 2008;Dong et al, 2013). Future research will address which learning mechanisms these tasks indeed recruit.…”

Section: Discussionmentioning

confidence: 97%

“…This may reflect that GluA2 3Y preserved spatial memory and the ability to discriminate the original conditioning context from new ones, but it could also suggest that GluA2-dependent AMPAR endocytosis is essential for fine-tuning hippocampal networks during abstraction processes; that is, the extrapolation of general patterns from specific experiences. These various possible contributions of GluA2/AMPAR trafficking to memory processes could explain why GluA2 3Y blocks reversal learning (Dong et al, 2013), reconsolidation (Rao-Ruiz et al, 2011), and extinction learning (Dalton et al, 2008;Dias et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…Concentrations and volumes (1 l per hemisphere) were based on previous studies (Bast et al, 2005;Migues et al, 2010;Dalton et al, 2012). For cell permeability, all peptides were fused to a sequence (YGRKKRRQRRR) derived from the transduction domain of the TAT protein.…”

Section: Methodsmentioning

confidence: 99%

“…The well characterized synthetic peptides GluA2 3Y and G2CT mimic two of these regions and attenuate activity-induced, but not constitutive, GluA2-dependent synaptic removal of AMPARs (Lee et al, 2002;Ahmadian et al, 2004;Wang et al, 2004;Yoon et al, 2009;Scholz et al, 2010;Dong et al, 2015). Without affecting basal synaptic transmission, GluA2 3Y blocks the induction of long-term depression (LTD), but not the induction of long-term potentiation (LTP), nor the acquisition or expression (i.e., retrieval), of conditioned fear memory (Ahmadian et al, 2004;Wang et al, 2004;Brebner et al, 2005;Dalton et al, 2008;Yu et al, 2008;Scholz et al, 2010;Rao-Ruiz et al, 2011;Bai et al, 2014;Dong et al, 2015). Similarly, G2CT effectively prevents GluA2/AMPAR internalization in live animals and slice preparations and blocks the formation of LTD (Griffiths et al, 2008;Yoon et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

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Blocking Synaptic Removal of GluA2-Containing AMPA Receptors Prevents the Natural Forgetting of Long-Term Memories

et al. 2016

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The neurobiological processes underpinning the natural forgetting of long-term memories are poorly understood. Based on the critical role of GluA2-containing AMPA receptors (GluA2/AMPARs) in long-term memory persistence, we tested in rats whether their synaptic removal underpins time-dependent memory loss. We found that blocking GluA2/AMPAR removal with the interference peptides GluA2 3Y or G2CT in the dorsal hippocampus during a memory retention interval prevented the normal forgetting of established, longterm object location memories, but did not affect their acquisition. The same intervention also preserved associative memories of food-reward conditioned place preference that would otherwise be lost over time. We then explored whether this forgetting process could play a part in behavioral phenomena involving time-dependent memory change. We found that infusing GluA2 3Y into the dorsal hippocampus during a 2 week retention interval blocked generalization of contextual fear expression, whereas infusing it into the infralimbic cortex after extinction of auditory fear prevented spontaneous recovery of the conditioned response. Exploring possible physiological mechanisms that could be involved in this form of memory decay, we found that bath application of GluA2 3Y prevented depotentiation, but not induction of long-term potentiation, in a hippocampal slice preparation. Together, these findings suggest that a decay-like forgetting process that involves the synaptic removal of GluA2/AMPARs erases consolidated long-term memories in the hippocampus and other brain structures over time. This well regulated forgetting process may critically contribute to establishing adaptive behavior, whereas its dysregulation could promote the decline of memory and cognition in neuropathological disorders.

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Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 97%