Persistence Of LTP Research Articles

The effectiveness and persistence of LTP on synaptic plasticity during sleep and sleep deprivation

The synaptic strength, which is crucial for memory and cognition function, is significantly influenced by sleep. According to earlier research, sound sleep is crucial for promoting connections between neural networks that are necessary for memory consolidation in the hippocampus. On the other hand, sleep deprivation can seriously impair the plasticity of our synapses. Sleep deprivation will disrupt LTP in region CA1 of the hippocampus, causing damage to neural connections. LTP has been proven to improve the connection between synapses, which will promote synaptic plasticity and so influence cognition function favorably. We also take a deeper look at LTP from a cellular and genetic perspective. In this review, we explore the detrimental effects of sleep deprivation on LTP stimulation and how they weaken synaptic plasticity and impair memory and learning performance. By studying LTP we can unravel the mysteries of brain function and the ability to learn and memory, and it can also give implications for understanding neurological disorders and advancing our knowledge of neurol system.

Dopaminergic modulation of the persistence of one-trial hippocampus-dependent memory.

The persistence of new memory traces in the hippocampus, encoded following appropriate activation of glutamatergic receptors and the induction of synaptic plasticity, can be influenced by heterosynaptic activation of neuromodulatory brain systems. We therefore investigated the effects of a hippocampus-specific blockade of dopamine D1/D5 receptors on the persistence of spatial memory encoded in one trial using a delayed matching-to-place (DMP) task in a watermaze in which rats learn a new escape location each day. A within-subjects design was used such that both short (20 min) and long (6 h) retention intervals, and both drug (SCH23390, a D1/D5 receptor antagonist) and vehicle (aCSF) infusions were tested on different days in the same animals. Bilateral intrahippocampal infusion of SCH23390 (5 microg in 1 microL per side) prior to trial 1 (encoding) caused a differential impairment as a function of memory delay-with no effect during trial 2 (memory retrieval) after a 20-min interval, but a block of memory at 6 h. Further experiments revealed that infusion of SCH23390 immediately after trial 1 had no effect on retention 6 h later, and the poor memory seen at long retention intervals when the drug was present at encoding was not due to a state-dependent failure of retrieval. These results suggest that activation of D1/D5 receptors during memory encoding is necessary for the formation of a persistent memory trace in the hippocampus. The complementary effects of D1/D5 receptor blockade on the persistence of LTP and the duration of memory are consistent with the idea that changes in synaptic strength underlie memory.

Heterosynaptic co-activation of glutamatergic and dopaminergic afferents is required to induce persistent long-term potentiation

The persistence of protein synthesis-dependent long-term potentiation (late-LTP) is thought to require heterosynaptic activation of both glutamate and neuromodulatory receptors in the hippocampus (Trends Neurosci. 21 (1998) 181; Proc. Nat. Acad. Sci. USA 93 (1996) 13445). The present series of experiments contrasts two alternative accounts of heterosynaptic activation. The original version of the synaptic-tag hypothesis of the variable persistence of LTP (Nature 385 (1997) 533) implied that neuromodulatory and glutamatergic activation could occur independently, albeit within a critical time-window; an alternative view is that there needs to be simultaneous co-activation of both receptors to trigger the up-regulation of relevant protein synthesis (Neuron 34 (2002) 235). Our findings include a replication, over 6 h post-LTP-induction, of earlier findings showing heterosynaptic influences on LTP persistence (Nature 385 (1997) 533; Neuropharmacology 37 (1998) 545). Specifically, ‘strong’ tetanisation with multiple trains of stimulation of one input pathway in a conventional hippocampal slice preparation induces a D1/D5 receptor-dependent form of late-LTP that enables ‘weak’ tetanic stimulation to induce late-LTP on an independent pathway. However, we also observed that when the first pathway was tetanised in the presence of AP5, not only was no LTP observed on that pathway, but there was also no rescue of late-LTP on the second pathway. Thus, it appears that DA receptors must be co-activated with NMDA receptors in a common pool of neurons to enable LTP persistence, although late-LTP can still be induced by selective activation of glutamatergic synapses if this occurs at time periods shortly before or shortly after this essential coactivation.

Hippocampal LTP Is Accompanied by Enhanced F-Actin Content within the Dendritic Spine that Is Essential for Late LTP Maintenance In Vivo

The dendritic spine is an important site of neuronal plasticity and contains extremely high levels of cytoskeletal actin. However, the dynamics of the actin cytoskeleton during synaptic plasticity and its in vivo function remain unclear. Here we used an in vivo dentate gyrus LTP model to show that LTP induction is associated with actin cytoskeletal reorganization characterized by a long-lasting increase in F-actin content within dendritic spines. This increase in F-actin content is dependent on NMDA receptor activation and involves the inactivation of actin depolymerizing factor/cofilin. Inhibition of actin polymerization with latrunculin A impaired late phase of LTP without affecting the initial amplitude and early maintenance of LTP. These observations suggest that mechanisms regulating the spine actin cytoskeleton contribute to the persistence of LTP.

Synaptic tagging: implications for late maintenance of hippocampal long-term potentiation

A novel property of hippocampal LTP, `variable persistence', has recently been described that is, we argue, relevant to the role of LTP in information storage. Specifically, new results indicate that a particular pattern of synaptic activation can give rise, either to a relatively short-lasting LTP, or to a longer-lasting LTP as a function of the history of activation of the neuron. This has led to the idea that the induction of LTP is associated with the setting of a `synaptic tag' at activated synapses, whose role is to sequester plasticity-related proteins that then serve to stabilize temporary synaptic changes and so extend their persistence. In this article, we outline the synaptic tag hypothesis, compare predictions it makes with those of other theories about the persistence of LTP, and speculate about the cellular identity of the tag. In addition, we outline the requirement for aminergic activation to induce late LTP and consider the functional implications of the synaptic tag hypothesis with respect to long-term memory.

Inhibition of protein kinase C blocks two components of LTP persistence, leaving initial potentiation intact

Protein kinase C (PKC) activity is increased following hippocampal long-term potentiation (LTP; Akers et al., 1986). A similar increase in PKC activity is measured following the induction of a long-lasting potentiation with abbreviated high-frequency stimulation (HFS) in combination with PKC-activating phorbol esters (Colley et al., 1989). Because phorbol esters have no effect on the initial potentiation produced with HFS, and because PKC activity appears to be related to the persistence of LTP and not to the initial change, we concluded that PKC regulates a post-initiation component of LTP. To define the time domain in which PKC activation is necessary for LTP, we studied the effect of the PKC inhibitors polymyxin B (PMXB) and 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7) micropressure ejected at different time points before and after the induction of LTP. LTP was produced in intact rats with HFS of the perforant path, and inhibitor ejections were made in the molecular layer of the dentate gyrus. PMXB, which at lower doses is a selective inhibitor of PKC, had no effect on initial potentiation, yet caused decay of the potentiated response to baseline within 2 hr. Decay occurred when PMXB was ejected 15 min before and 15 and 30 min after HFS. PMXB, at either low or high doses, was ineffective in blocking LTP persistence at time points greater than 30 min after HFS. Low doses of H-7 produced similar effects to those of PMXB. However, in contrast to a high dose of PMXB, a high dose of H-7 inhibited the persistence of LTP when delivered 240 min after HFS.(ABSTRACT TRUNCATED AT 250 WORDS)

The two major phosphoproteins in growth cones are probably identical to two protein kinase C substrates correlated with persistence of long- term potentiation

Regulation of neural protein kinase C (PKC) activity appears to directly affect the persistence of long-term potentiation (LTP; Akers and Routtenberg, 1985; Lovinger et al., 1985, 1986, 1987; Routtenberg et al., 1985, 1986; Akers et al., 1986; Linden et al., 1987), a model of neural plasticity (Bliss and Lomo, 1973). In addition, the in vitro phosphorylation of a brain-specific PKC substrate, protein F1 (Mr 47 kDa, pl 4.5), has been directly correlated with persistence of LTP (Lovinger et al., 1986). Because PKC has been implicated in neurite outgrowth and is present at high levels in growth cone-rich areas of fetal brain, we investigated and characterized PKC substrates in a preparation of isolated nerve growth cone fragments from fetal rat brain and compared them with PKC substrates found in adult rat hippocampus. Four major proteins in the growth cone preparation showed endogenous phosphorylation levels at least 10-fold greater than any other phosphoproteins. Three of these 4 phosphoproteins, termed pp40, pp46, and pp80 (Katz et al., 1985), were phosphorylated by exogenous PKC in a dose-dependent manner, indicating that PKC activity might be of particular importance relative to other kinases in growth cone function. The 2 most highly labeled PKC substrates, pp46 and pp80, comigrated on 2-dimensional gels with the adult hippocampal proteins F1 and "80k" (Mr 78-80 kDa, pl 4.0), respectively. In addition, similarities in charge heterogeneity, 2-dimensional phosphopeptide maps, and increased phosphorylation in the presence of exogenous PKC or PKC stimulators suggest that protein F1 and 80k are highly homologous to, if not identical to, pp46 and pp80, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)