AMPA Receptors: A Key Piece in the Puzzle of Memory Retrieval

Abstract

Retrieval constitutes a highly regulated and dynamic phase in memory processing. Its rapid temporal scales require a coordinated molecular chain of events at the synaptic level that support transient memory trace reactivation. AMPA receptors (AMPAR) drive the majority of excitatory transmission in the brain and its dynamic features match the singular fast timescales of memory retrieval. Here we provide a review on AMPAR contribution to memory retrieval regarding its dynamic movements along the synaptic compartments, its changes in receptor number and subunit composition that take place in activity dependent processes associated with retrieval. We highlight on the differential regulations exerted by AMPAR subunits in plasticity processes and its impact on memory recall.

Functional excitatory to inhibitory synaptic imbalance and loss of cognitive performance in people with Alzheimer’s disease neuropathologic change

“…Our data showed that the e E/I ratio in the hippocampus was not different in MCI or AD; however, lower amplitudes of GABA A Rs and AMPARs currents in the hippocampus were associated with lower cognitive scores, indicating that hippocampal atrophy, with total loss of excitatory and inhibitory synapses, correlates better with cognitive impairment, as observed in hippocampal sclerosis studies [ 80 ]. This is also in agreement with strong evidence supporting the relationship between positive modulation of hippocampal AMPARs [ 50 , 56 , 68 , 93 ] with better cognition. In contrast, we found that a gain of function of AMPARs in parallel with GABAergic deficits lead to a striking pro-excitatory shift of the E/I balance in the TCx of AD individuals across various levels of analyses.…”

Synaptic remodeling of GluA1 and GluA2 expression in the nucleus accumbens promotes susceptibility to cognitive deficits concomitant with downstream GSK3β mediated neurotoxicity in female mice during abstinence from voluntary oral methamphetamine

“…Hippocampal synaptic fractions were analyzed for expression of to investigate sex differences in molecular mechanisms underlying VOMA induced working memory deficits. GluA1 and GluA2 are markers known to be involved in synaptic plasticity for short-term and long-term memory respectively [ 40 , 41 ]. A two-way repeated measures ANOVA of hippocampal GluA1 expression [ Fig.…”

“…However, the AMPAR signaling pathways that drive synaptic plasticity have not been fully investigated in MA-induced memory deficits. GluA1 and GluA2 are AMPARs known to be involved in synaptic plasticity processes with direct implications in learning and memory [ 40 , 41 ]. AMPAR trafficking is modulated by PKM ζ to sustain LTP processes [ 42 , 43 ] and conversly by glycogen synthase kinase 3 β (GSK3 β ) to promote LTD [ 44 ].…”

“…MA is known to produce neurotoxic excitotoxicity through glutamate signaling with downstream activation of cell death and inflammatory pathways [ 55 , 56 ]. GSK3 β signaling is heavily implicated in neuronal apoptosis, downstream neuroinflammatory signaling cascades as well as synaptic plasticity processes [ 41 , 44 , 46 – 48 , 57 ]. Little is known regarding the role of GSK3 β regulation of calcium and glutamate-dependent synaptic plasticity in both clinical MA abuse and rodent models of MA abuse.…”

Cognitive rescue in aging through prior training in rats

“…At the molecular level, encoding can trigger a cascade of signal induction and transduction [ 50 ]. For initial induction, findings have consistently suggested the importance of glutamatergic receptors, such as NMDA and AMPA receptors in forming short- and long-term memory [ 51 , 52 ]. However, partially dissociative molecular mechanisms for short-term and long-term memory have been reported.…”