NMDA receptor antagonists sustain LTP and spatial memory: active processes mediate LTP decay

Villarreal, Desiree M.; Do, Viet; Haddad, Evelyn; Derrick, Brian E.

doi:10.1038/nn776

Cited by 175 publications

(126 citation statements)

References 35 publications

Supporting

Mentioning

114

Contrasting

Unclassified

Order By: Relevance

“…The competitive NMDAR antagonist CPP was injected intraperitoneally at a dose of 10 mg/kg. Under these conditions, NMDAR activation and LTP induction are blocked for at least 8 hr (Abraham and Mason, 1988;Villarreal et al, 2002). As shown in Figure 3A, BDNF induced a robust potentiation of the fEPSP slope and population spike amplitude in the CPP-treated animals ( p Ͻ 0.05; n ϭ 6).…”

Section: Bdnf-ltp Is Nmda Receptor-independentmentioning

confidence: 82%

Brain-Derived Neurotrophic Factor Triggers Transcription-Dependent, Late Phase Long-Term PotentiationIn Vivo

et al. 2002

View full text Add to dashboard Cite

Acute intrahippocampal infusion of brain-derived neurotrophic factor (BDNF) leads to long-term potentiation (BDNF-LTP) of synaptic transmission at medial perforant path3granule cell synapses in the rat dentate gyrus. Endogenous BDNF is implicated in the maintenance of high-frequency stimulation-induced LTP (HFS-LTP). However, the relationship between exogenous BDNF-LTP and HFS-LTP is unclear. First, we found that BDNF-LTP, like HFS-LTP, is associated with enhancement in both synaptic strength and granule cell excitability (EPSP-spike coupling). Second, treatment with a competitive NMDA receptor (NMDAR) antagonist blocked HFS-LTP but had no effect on the development or magnitude of BDNF-LTP. Thus, NMDAR activation is not required for the induction or expression of BDNF-LTP. Formation of stable, late phase HFS-LTP requires mRNA synthesis and is coupled to upregulation of the immediate early gene activityregulated cytoskeleton-associated protein (Arc). Local infusion of the transcription inhibitor actinomycin D (ACD) 1 hr before or immediately before BDNF infusion inhibited BDNF-LTP and upregulation of Arc protein expression. ACD applied 2 hr after BDNF infusion had no effect, defining a critical time window of transcription-dependent synaptic strengthening. Finally, the functional role of BDNF-LTP was assessed in occlusion experiments with HFS-LTP. HFS-LTP was induced, and BDNF was infused at time points corresponding to early phase (1 hr) or late phase (4 hr) HFS-LTP. BDNF applied during the early phase led to normal BDNF-LTP. In contrast, BDNF-LTP was completely occluded during the late phase. The results strongly support a role for BDNF in triggering transcription-dependent, late phase LTP in the intact adult brain.

show abstract

Section: Bdnf-ltp Is Nmda Receptor-independentmentioning

confidence: 82%

Brain-Derived Neurotrophic Factor Triggers Transcription-Dependent, Late Phase Long-Term PotentiationIn Vivo

et al. 2002

View full text Add to dashboard Cite

show abstract

“…The (±)CPP dose of 5mg/kg has been shown to disrupt synaptic plasticity processes in the hippocampal formation 12-24 hours following i.p. administration [34].…”

Section: Drugs and Dosage Justificationmentioning

confidence: 99%

The effects of extinction training in reducing the reinstatement of drug-seeking behavior: Involvement of NMDA receptors

Kelamangalath

Swant

Stramiello

et al. 2007

Behavioural Brain Research

View full text Add to dashboard Cite

Although the process of extinction has been well documented for various forms of behavioral responses, the effects of extinction on the reinstatement of drug seeking behavior are relatively understudied. In this report, the effectiveness of an extinction training protocol to reduce primed reinstatement responses was compared with the effectiveness of an equivalent period of enforced abstinence. We found that extinction training performed in the drug taking environment significantly reduced reinstatement behavior subsequently primed by either contextual cues, conditioned cues, or cocaine infusion. The ability of extinction to reduce cocaine primed reinstatement was blocked by the systemic administration of the competitive NMDAR antagonist ((±)CPP, 5 mg/kg i.p.) administered prior to each extinction training session. Interestingly, this pharmacological intervention had no impact on the effectiveness of extinction to reduce drug-seeking behavior primed by either contextual cues or conditioned cues. These results suggest that an extinction training experience involves multiple mechanisms that can be dissociated into nonNMDAR and NMDAR dependent components with respect to the type of reinstatement (i.e. context-, CS-, or drug-induced) being assessed.

show abstract

“…Two recent studies indicate that LTP persistence over days is in fact subject to ongoing regulation. In one study, LTP (CPP) was injected once daily (Villarreal et al 2001). This treatment also prevented forgetting a learned spatial task.…”

Section: How Long Will Ltp Persist?mentioning

confidence: 99%

“…Although it is potentially misleading to compare the properties of monosynaptic LTP with the properties of memory stored in a network of synapses, none the less the theory has a certain appeal that will seed experimental tests. Indeed, a recent study reported that a treatment that prolonged LTP retention in the dentate gyrus also prolonged memory retention for a hippocampus-dependent spatial memory task (Villarreal et al 2001). Conversely, reduction of LTP maintenance in zif268-knock out mice was associated with reduced retention on several diverse memory tasks (Jones et al 2001).…”

Section: Questions For the Futurementioning

confidence: 99%

How long will long-term potentiation last?

Abraham

2003

Phil. Trans. R. Soc. Lond. B

231

165

View full text Add to dashboard Cite

The paramount feature of long-term potentiation (LTP) as a memory mechanism is its characteristic persistence over time. Although the basic phenomenology of LTP persistence was established 30 years ago, new insights have emerged recently about the extent of LTP persistence and its regulation by activity and experience. Thus, it is now evident that LTP, at least in the dentate gyrus, can either be decremental, lasting from hours to weeks, or stable, lasting months or longer. Although mechanisms engaged during the induction of LTP regulate its subsequent persistence, the maintenance of LTP is also governed by activity patterns post-induction, whether induced experimentally or generated by experience. These new findings establish dentate gyrus LTP as a useful model system for studying the mechanisms governing the induction, maintenance and interference with long-term memory, including very long-term memory lasting months or longer. The challenge is to study LTP persistence in other brain areas, and to relate, if possible, the properties and regulation of LTP maintenance to these same properties of the information that is actually stored in those regions.Keywords: long-term potentiation; hippocampus; maintenance mechanisms; enriched environment; neurogenesis; metaplasticitySince the pioneering studies performed 30 years ago by Tim Bliss, Terje Lømo and Tony Gardner-Medwin (Bliss & Lømo 1973;Bliss & Gardner-Medwin 1973), LTP has generated enormous interest as a potential memory mechanism. This is because LTP exhibits numerous properties expected of an associative memory mechanism, such as rapid induction, input specificity, associative interactions, persistence, and dependence on correlated preand postsynaptic activity. The close similarity between these features and those of the learning rule of Hebb (1949) has added lustre to the LTP phenomenon. In addition, there is important yet complex regulation of LTP by prior synaptic activity (metaplasticity), neighbouring afferents (e.g. synaptic tagging), and state variables such as levels of stress hormones and activity in neuromodulatory transmitter systems (see Martin et al. (2000) for a review of these properties of LTP). It can be argued, however, that among all these intriguing and important characteristics, the paramount feature that defines LTP as a potential memory mechanism is its persistence over time. Thus, although short-lasting frequency potentiation of synaptic potentials was described in the hippocampus many years ago, it was not until the discovery of LTP that researchers seriously considered that a model system for studying synaptic mechanisms of mammalian memory had been established. It is curious, therefore, that despite the fundamental importance of LTP maintenance over days and weeks, relatively few studies have addressed its mechanisms and regulation. The purpose of this review is to summarize the data from experiments charting how long LTP can last, and then to address the factors that regulate how long LTP will in fact persist under various conditi...

show abstract

NMDA receptor antagonists sustain LTP and spatial memory: active processes mediate LTP decay

Cited by 175 publications

References 35 publications

Brain-Derived Neurotrophic Factor Triggers Transcription-Dependent, Late Phase Long-Term PotentiationIn Vivo

Brain-Derived Neurotrophic Factor Triggers Transcription-Dependent, Late Phase Long-Term PotentiationIn Vivo

The effects of extinction training in reducing the reinstatement of drug-seeking behavior: Involvement of NMDA receptors

How long will long-term potentiation last?

Contact Info

Product

Resources

About