The Extracellular Signal-Regulated Kinase Cascade Is Required for NMDA Receptor-Independent LTP in Area CA1 But Not Area CA3 of the Hippocampus

Abstract

Activation of extracellular signal-regulated kinase (ERK) has been shown to be necessary for NMDA receptor-dependent long-term potentiation (LTP). We studied the role of ERK in three forms of NMDA receptor-independent LTP: LTP induced by very high-frequency stimulation (200 Hz-LTP), LTP induced by the K(+) channel blocker tetraethylammonium (TEA) (TEA-LTP), and mossy fiber (MF) LTP (MF-LTP). We found that ERK was activated in area CA1 after the induction of both 200 Hz-LTP and TEA-LTP and that this activation required the influx of Ca(2+) through voltage-gated Ca(2+) channels. Inhibition of the ERK signaling cascade with either PD 098059 or U0126 prevented the induction of both 200 Hz-LTP and TEA-LTP in area CA1. In contrast, neither PD 098059 nor U0126 prevented MF-LTP in area CA3 induced by either brief or long trains of high-frequency stimulation. U0126 also did not prevent forskolin-induced potentiation in area CA3. However, incubation of slices with forskolin, an activator of the cAMP-dependent protein kinase (PKA) cascade, did result in increases in active ERK and cAMP response element-binding protein (CREB) phosphorylation in area CA3. The forskolin-induced increase in active ERK was inhibited by U0126, whereas the increase in CREB phosphorylation was not, which suggests that in area CA3 the PKA cascade is not coupled to CREB phosphorylation via ERK. Overall, our observations indicate that activation of the ERK signaling cascade is necessary for NMDA receptor-independent LTP in area CA1 but not in area CA3 and suggest a divergence in the signaling cascades underlying NMDA receptor-independent LTP in these hippocampal subregions.

Alteration of synaptic plasticity in rat dorsal striatum induced by chronic ethanol intake and withdrawal via ERK pathway

“…Although it has been previously shown that ERK phosphorylation is required for both LTP [9,10] and LTD [26,11] in hippocampal CA1 as well as LTD in the cerebellum [8] and LTP in other cortical areas [12] , we provide the first evidence that ERK activation is required for striatal LTD induction.…”

“…For example, stimuli inducing LTP in area CA1 of the hippocampus potently activate ERK [8] , whereas pharmacological inhibition of MEK, an upstream activator of ERK, inhibits LTP [8,9] . The participation of ERK in synaptic plasticity has also been found in other brain regions [10,11,12] (eg, LTD in the cerebellum and LTP in the visual cortex).…”

Chronic CXCL10 alters the level of activated ERK1/2 and transcriptional factors CREB and NF-κB in hippocampal neuronal cell culture

“…These results show that chronic exposure CXCL10 alters the ERK1/2 pathway by increasing both the level of total ERK1/2 and the level of the activated form (pERK1/2). The increase in level of the activated form of ERK (∼25-70%) observed in the CXCL10-treated cultures is comparable to the increase produced by high frequency stimulation paradigms used to induce long-term potentiation (LTP) in the hippocampus, a cellular model of memory and learning (Kanterewicz et al, 2000). Therefore, the effects of CXCL10 are in a biologically relevant range.…”

Caffeine‐mediated BDNF release regulates long‐term synaptic plasticity through activation of IRS2 signaling

“…To identify the pathway(s) responsible for BDNF‐mediated CAF LTP, we inhibited three downstream BDNF/TrkB signaling pathways involved in hippocampal LTP: the phospholipase Cγ (PLCγ) pathway, the Ras‐mitogen‐activated protein kinase (MAPK) pathway and the PI3K pathway (English & Sweatt 1996; Kanterewicz et al 2000; Man et al 2003; Wang et al 2003). Inhibition of PLCγ (10‐μM U73122; n  = 7; N  = 3; Fig.…”