ERK Pathway Activation Bidirectionally Affects Visual Recognition Memory and Synaptic Plasticity in the Perirhinal Cortex

Abstract

ERK 1,2 pathway mediates experience-dependent gene transcription in neurons and several studies have identified its pivotal role in experience-dependent synaptic plasticity and in forms of long term memory involving hippocampus, amygdala, or striatum. The perirhinal cortex (PRHC) plays an essential role in familiarity-based object recognition memory. It is still unknown whether ERK activation in PRHC is necessary for recognition memory consolidation. Most important, it is unknown whether by modulating the gain of the ERK pathway it is possible to bidirectionally affect visual recognition memory and PRHC synaptic plasticity. We have first pharmacologically blocked ERK activation in the PRHC of adult mice and found that this was sufficient to impair long term recognition memory in a familiarity-based task, the object recognition task (ORT). We have then tested performance in the ORT in Ras-GRF1 knock-out (KO) mice, which exhibit a reduced activation of ERK by neuronal activity, and in ERK1 KO mice, which have an increased activation of ERK2 and exhibit enhanced striatal plasticity and striatal mediated memory. We found that Ras-GRF1 KO mice have normal short term memory but display a long term memory deficit; memory reconsolidation is also impaired. On the contrary, ERK1 KO mice exhibit a better performance than WT mice at 72 h retention interval, suggesting a longer lasting recognition memory. In parallel with behavioral data, LTD was strongly reduced and LTP was significantly smaller in PRHC slices from Ras-GRF1 KO than in WT mice while enhanced LTP and LTD were found in PRHC slices from ERK1 KO mice.

Acquisition of Contextual Discrimination Involves the Appearance of a RAS-GRF1/p38 Mitogen-activated Protein (MAP) Kinase-mediated Signaling Pathway That Promotes Long Term Potentiation (LTP)

“…Moreover, GRF1 mediates dopamine signaling through ERK activation in the striatum (37), whereas it is a poor mediator of NMDA receptor activation of ERK in the CA1 (5). In addition, RAS-GRF1 affects visual recognition memory and both LTP and LTD in the perirhinal cortex via regulation of ERK (38). Finally, RAS-GRF1 mediates CP-AMPAR activation of ERK in the cortex at 1 month of age (12), but p38 activation starting at 2 months of age in the CA1, but not CA3 or dentate gyrus, regions of the hippocampus.…”

CaMKII-dependent dendrite ramification and spine generation promote spatial training-induced memory improvement in a rat model of sporadic Alzheimer's disease

“…We also measured the level and the activity-dependent phosphorylation of CaMKII, cAMP-dependent protein kinase (PKA), and extracellular signal-related kinase 1/2 (ERK1/2), which are involved in dendrite remodeling (Hudmon and Schulman, 2002;Caiati et al, 2013;Silingardi et al, 2011). The results showed that the level of phosphorylated CaMKII at Thr286 (pCaMKII) was remarkably increased in hippocampus of T-hHcy rats, whereas the levels of total CaMKII, total ERK1/2 and pERK1/2, PKAa catalytic subunit (PKAa-cat), and PKA Ib regulatory subunit (PKA Ib-reg) were not changed by training (Fig.…”

Extracellular Signal-Regulated Kinase in the Basolateral Amygdala, but not the Nucleus Accumbens Core, is Critical for Context-Response-Cocaine Memory Reconsolidation in Rats

“…In turn, ERK phosphorylates several transcription factors (Goodman, 1990;Impey et al, 1999;Sgambato et al, 1998) that have also been implicated in drug-memory reconsolidation, including the cAMP response element binding protein (CREB) and E twenty-six (ETS)-like transcription factor 1 (Miller and Marshall, 2005). Furthermore, evidence suggests that ERK itself is required for the reconsolidation of object recognition memories (Kelly et al, 2003;Silingardi et al, 2011), conditioned-fear associations (Duvarci et al, 2005), and importantly, Pavlovian cocainerelated memories that underlie the expression of cocaineconditioned place preference (CPP; Miller and Marshall 2005;Valjent et al, 2006). However, the role of ERK in the reconsolidation of contextual drug memories has not been assessed in an instrumental paradigm.…”