Primed Facilitation of Homosynaptic Long-Term Depression and Depotentiation in Rat Hippocampus

Abstract

Previous studies have demonstrated that prior synaptic activity can influence the subsequent induction of synaptic plasticity in the brain. Such temporal modulation of synaptic plasticity has been called "metaplasticity." In this report, we describe the facilitatory effects of high-frequency stimulation on the induction of homosynaptic long-term depression (LTD) in the CA1 region of the rat hippocampus. The LTD induced by low-frequency stimulation (1 Hz) protocols was found to be homosynaptic and NMDA receptor-dependent. The facilitatory effects of the high-frequency stimulation-induced priming event itself were found to be NMDA receptor-independent and to have a duration of at least 90 min. The effects of priming also were heterosynaptic, because the induction of synaptic plasticity by low-frequency stimulation was enhanced at an unprimed synaptic pathway after the priming of an independent pathway. In addition to enhancing LTD, priming also enhanced the reversal of long-term potentiation elicited by a 5 Hz depotentiation protocol. Our results provide examples of how metaplasticity may play a key role in the ongoing modulation of the induction and stabilization of alterations in synaptic strength.

Heterosynaptic metaplasticity in the hippocampus in vivo : A BCM-like modifiable threshold for LTP

“…We observed that the LTP threshold is indeed raised after tetanization heterosynaptically, confirming the previous findings in CA1 in vitro (6,7). Unlike in CA1 slices, however, this effect was blocked by an NMDA receptor antagonist.…”

“…A critical parameter of the model, the modification threshold, has the key feature of varying in a cell-wide (heterosynaptic) fashion, as directed by the prior history of activity in the neuron. Although there is considerable evidence that the modification threshold can be manipulated homosynaptically by prior activation of glutamate receptors (5), only a few reports from hippocampal slices have shown evidence for heterosynaptic changes (6,7,19). In a different approach, when young rats were reared in the dark, there was a delay of the shift in the modification threshold toward reduced LTD and enhanced LTP that normally occurs during development in the visual cortex (20).…”

“…4 and 5). Recent experiments in hippocampal slices have, however, demonstrated that repeated tetanization of one input pathway can cause similar effects heterosynaptically, in an NMDA-receptor-independent manner (6,7). Whether these effects are induced by postsynaptic cell firing, however, has not been addressed.…”

A Nitric Oxide-Independent and β-Adrenergic Receptor-Sensitive Form of Metaplasticity Limits θ-Frequency Stimulation-Induced LTP in the Hippocampal CA1 Region

“…However, as originally envisioned in the model, shifts in m produce a cell-wide (i.e., heterosynaptic) change in the amounts of coincident synaptic activity needed for LTP or LTD induction (Bienenstock et al 1982;Bear et al 1987); yet in our experiments we observed that the inhibition of LTP by prior 5-Hz stimulation was homosynaptic (see also Huang et al 1992). Because other studies have found evidence for heterosynaptic changes in m (Holland and Wagner 1998), it seems likely that excitatory synapses onto pyramidal cells in the CA1 region of the hippocampus express both homosynaptic and heterosynaptic forms of metaplasticity.…”

Metaplastic Regulation of Long-Term Potentiation/Long-Term Depression Threshold by Activity-Dependent Changes of NR2A/NR2B Ratio

“…In addition, the metaplasticity that we observed here is homosynaptic in nature. It still remains to be determined whether the activity at the CA1 neurons that we studied could also induce the same affect on subsequent plasticity at neighboring synapses, as is predicted by the BCM theory and supported by recent studies (Holland and Wagner, 1998;Wang and Wagner, 1999;Abraham et al, 2001;Roth-Alpermann et al, 2006).…”