Spike‐timing‐dependent plasticity at resting and conditioned lateral perforant path synapses on granule cells in the dentate gyrus: different roles of N‐methyl‐d‐aspartate and group I metabotropic glutamate receptors

Abstract

We examined the mechanisms underlying spike-timing-dependent plasticity induction at resting and conditioned lateral perforant pathway (LPP) synapses in the rat dentate gyrus. Two stimulating electrodes were placed in the outer third of the molecular layer and in the granule cell layer in hippocampal slices to evoke field excitatory postsynaptic potentials (fEPSPs) and antidromic field somatic spikes (afSSs), respectively. Long-term potentiation (LTP) of LPP synapses was induced by paired stimulation with fEPSP preceding afSS. Reversal of the temporal order of fEPSP and afSS stimulation resulted in long-term depression (LTD). Induction of LTP or LTD was blocked by D,L-2-amino-5-phosphonopentanoic acid (AP5), showing that both effects were N-methyl-D-aspartate receptor (NMDAR)-dependent. Induction of LTP was also blocked by inhibitors of calcium-calmodulin kinase II, protein kinase C or mitogen-activated/extracellular-signal regulated kinase, suggesting that these are downstream effectors of NMDAR activation, whereas induction of LTD was blocked by inhibitors of protein kinase C and protein phosphatase 2B. At LPP synapses previously potentiated by high-frequency stimulation or depressed by low-frequency stimulation, paired fEPSP-afSS stimulation resulted in 'de-depression' at depressed LPP synapses but had no effect on potentiated synapses, whereas reversal of the temporal order of fEPSP-afSS stimulation resulted in 'de-potentiation' at potentiated synapses but had no effect on depressed synapses. Induction of de-depression and de-potentiation was unaffected by ap5 but was blocked by 2-methyl-6-(phenylethynyl) pyridine hydrochloride, a group I metabotropic glutamate receptor blocker, showing that both were NMDAR-independent but group I metabotropic glutamate receptor-dependent. In conclusion, our results show that spike-timing-dependent plasticity can occur at both resting and conditioned LPP synapses, its induction in the former case being NMDAR-dependent and, in the latter, group I metabotropic glutamate receptor-dependent.

Inhibition of associative long-term depression by activation of β-adrenergic receptors in rat hippocampal CA1 synapses

“…We previously reported that associative LTP can be induced by a pairing protocol in hippocampal CA1 and lateral perforant pathway [13,14]. We have also demonstrated that results obtained with the extracellular recording technique are compatible with those obtained with the whole-cell recording technique, in which LTP of the weak pathway is induced by pairing it with post-synaptic spiking.…”

Subthreshold Dendritic Signal Processing and Coincidence Detection in Dentate Gyrus Granule Cells

“…If distal synaptic inputs are activated within a narrow time window of less than ϳ10 ms, they will sum up and effectively depolarize the dendritic membrane potential. As a consequence, activation of dendritic voltage-dependent Ca 2ϩ channels (Blaxter et al, 1989) and NMDA receptors (Lin et al, 2006) will depend on highly coincident synaptic potentials.…”

“…This was essentially independent of whether synapses were placed on the dendritic shaft or on spines, because the electrical properties of synaptic spines attenuated the dendritic EPSPs by Ͻ10%. This would indicate that few synapses activated within a narrow time window of Ͻ10 ms may be able to relieve voltage-dependent Mg 2ϩ block and trigger local dendritic Ca 2ϩ influx via NMDA receptors, known to be important for the induction of synaptic plasticity (Golding et al, 2002;Lin et al, 2006).…”

Role of Extracellular Signal-Regulated Kinase in Synaptic Transmission and Plasticity of a Nociceptive Input on Capsular Central Amygdaloid Neurons in Normal and Acid-Induced Muscle Pain Mice

“…Since ERK activation is essential for the induction of certain forms of LTP at cortical synapses (Impey et al, 1999;Lin et al, 2003Lin et al, , 2006, we tested whether ERK-dependent LTP could be induced by high-frequency stimulation (HFS) at PBA-CeAC synapses in slices from normal mice and whether LTP induction might share common mechanisms with induction of PKC-ERKdependent potentiation by PDA and with postsynaptic enhancement of PBA-CeAC EPSCs in AIMP animals. As shown in Figure 8 A (squares), after application of three trains of HFS at 100 Hz to slices from normal mice, the PBA-CeAC EPSP was significantly potentiated to 191 Ϯ 30% of baseline (n ϭ 9 cells tested, p Ͻ 0.05, paired t test), and potentiation lasted for at least 30 min.…”

“…These plastic changes in synaptic function in the pain-related CNS areas are considered to be a part of the cellular mechanisms underlying the development of central sensitization in chronic pain (Ji et al, 2003). At some cortical synapses, LTP induction requires activation of extracellular signal-regulated kinase (ERK) (Impey et al, 1999;Giovannini et al, 2001;Lin et al, 2003Lin et al, , 2006. Since a biochemical hallmark of chronic pain is increased levels of phosphorylated ERK (pERK) in the DH (Ji et al, 1999;Garry et al, 2005;Wei et al, 2006) (for review, see , it is likely that ERK activity triggered by repeated and excessive noxious stimuli might induce LTP of nociceptive inputs onto DH neurons, thereby resulting in central sensitization.…”