Disease relevance of Long-Term Potentiation

• Perforant path long-term potentiation (LTP) in intact mouse hippocampal dentate gyrus increased the neuron-specific, growth-associated protein GAP-43 mRNA in hilar cells 3 days after tetanus, but surprisingly not in granule cells, the perforant path target [1].
• HIV-1 Tat inhibits long-term potentiation and attenuates spatial learning [corrected] [2].
• In animal models of diabetes mellitus, such as the streptozotocin-diabetic rat (STZ-rat), spatial learning impairments develop in parallel with a reduced expression of long-term potentiation (LTP) and enhanced expression of long-term depression (LTD) in the hippocampus [3].
• In superficial layers of the lumbar spinal dorsal horn, N-methyl-D-aspartate-dependent long-term potentiation (LTP) of C fibre-evoked field potentials, a synaptic model of central sensitisation and hyperalgesia, ensues the application of electrical high-frequency, high-intensity conditioning stimulation to the sciatic nerve [4].
• Sequential activation of soluble guanylate cyclase, protein kinase G and cGMP-degrading phosphodiesterase is necessary for proper induction of long-term potentiation in CA1 of hippocampus. Alterations in hyperammonemia [5].

Psychiatry related information on Long-Term Potentiation

• Mice with targeted disruption of neuronal NO synthase (nNOS) display grossly normal appearance, locomotor activity, breeding, long-term potentiation and long-term depression [6].
• Prenatal exposure to a cannabinoid agonist produces memory deficits linked to dysfunction in hippocampal long-term potentiation and glutamate release [7].
• Here we demonstrate that the Mecp2-null mouse model of Rett syndrome shows an age-dependent impairment in hippocampal CA1 long-term potentiation induced by tetanic or theta-burst stimulation [8].
• AM251, a selective antagonist of the CB1 receptor, inhibits the induction of long-term potentiation and induces retrograde amnesia in rats [9].
• Impairment in hippocampal long-term potentiation in mice under-expressing the Alzheimer's disease related gene presenilin-1 [10].

High impact information on Long-Term Potentiation

• Regulation of neuronal plasticity by phosphorylation of synapsin I and of postsynaptic substrates necessary for long-term potentiation is another dynamic area of investigation [11].
• Whole-cell recordings from amygdala slices that are isolated from stathmin knockout mice show deficits in spike-timing-dependent long-term potentiation (LTP) [12].
• Extensive studies have shown that long-term potentiation (LTP) of the excitatory postsynaptic current (EPSC) through glutamate receptors is induced by activation of N-methyl-D-asparate receptor (NMDA-R)--the coincidence detector--and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) [13].
• GRPR-deficient mice showed decreased inhibition of principal neurons by the interneurons, enhanced long-term potentiation (LTP), and greater and more persistent long-term fear memory [14].
• Mice with a targeted loss-of-function mutation in Rab3a have defects in Ca(2+)-dependent synaptic transmission: the number of vesicles released in response to an action potential is greater than in wildtype mice, resulting in greater synaptic depression and the abolishment of CA3 mossy-fiber long term potentiation [15].

Chemical compound and disease context of Long-Term Potentiation

• Its expression is brain specific and up-regulated by neuronal activity such as kainate stimulation and tetanus stimulation evoking hippocampal CA1 long-term potentiation [16].
• Transgenic mice expressing HIV-1 coat glycoprotein gp120 in brain glial cells were previously shown to display AIDS dementia-like neuropathological changes and reduced hippocampal long-term potentiation [17].
• Application of a membrane-permeant guanosine-3',5'-cyclic monophosphate analogue during tetanus fails to compensate for this deficit, suggesting that nitric oxide produced by endothelial nitric oxide synthase may affect long-term potentiation through a cascade that does not include guanylyl cyclase [18].
• 4. The nitric oxide synthase blocker, NG-nitro-L-arginine methyl ester (L-NAME, 100 microM) was added prior to the tetanic stimulation of the preganglionic nerves at 30 Hz for 20 s, a procedure known to produce both post-tetanic potentiation and long-term potentiation of synaptic transmission through the ganglion [19].
• The inactive enantiomer of the nitric oxide synthase inhibitor, N(G)-nitro-D-arginine methyl ester (10 microM), failed to inhibit the long-term potentiation when given 30 min before the tetanus [20].

Biological context of Long-Term Potentiation

• Electrophysiology reveals that mice lacking synapsin I exhibit a selective increase in paired pulse facilitation, with no major alterations in other synaptic parameters such as long-term potentiation [21].
• Protein phosphorylation of glutamate receptors by protein kinase C and cyclic AMP-dependent protein kinase (PKA) has been suggested to regulate their function, possibly playing a prominent role in certain forms of synaptic plasticity such as long-term potentiation and long-term depression [22].
• These results show that the loss of the nociceptin receptor results in a gain-of-function mutation in both the memory process and the long-term potentiation mechanism in CA1, perhaps as a result of altered intracellular signal transduction systems in neurons [23].
• Here we investigate the role of the neural cell adhesion molecules L1 and NCAM in hippocampal long-term potentiation (LTP), a sustained-use-dependent increase in synaptic efficacy that has been implicated in learning and memory [24].
• We show that two different inhibitors of the ERK pathway suppress the induction of two forms of long-term potentiation (LTP) in rat cortical slices and that their intracortical administration to monocularly deprived rats prevents the shift in ocular dominance towards the nondeprived eye [25].

Anatomical context of Long-Term Potentiation

• Recently, Hopkins and Johnston demonstrated that noradrenaline enhances the magnitude, duration and probability of induction of long-term potentiation (LTP) at mossy fibre synapses in the hippocampal formation, and LTP is widely believed to be a cellular substrate for aspects of memory [26].
• Unlike CREB alpha/delta-deficient mice whose main defect is in long-term potentiation, the widespread abnormalities in ATF-2 mutant mice demonstrate its absolute requirement for skeletal and central nervous system development, and for maximal induction of select genes with CRE sites, such as E-selectin [27].
• B-50 has been implicated in the regulation of polyphosphoinositide metabolism and calmodulin binding, and in the mechanisms of neurite outgrowth, long-term potentiation and transmitter release [28].
• In many regions of the cerebral cortex, Ca2+ influx through NMDA (N-methyl-D-aspartate) sensitive glutamate receptors (NMDA receptors) can trigger two forms of synaptic plasticity: long-term depression (LTD) and long-term potentiation (LTP) [29].
• These neurons are nocispecific, support long-term potentiation and appear to downregulate the K(+)-Cl(-) exporter channel KCC2 following peripheral nerve damage, leading to increased excitability [30].

Associations of Long-Term Potentiation with chemical compounds

• Nitric oxide acts directly in the presynaptic neuron to produce long-term potentiation in cultured hippocampal neurons [31].
• Drugs that antagonize N-methyl-D-aspartate (NMDA)-receptor activity, which is required for long-term potentiation (LTP) at various hippocampal synapses, block LTP and impair watermaze learning [32].
• Furthermore, dopamine modulates long-term potentiation, a putative cellular mechanism underlying plasticity [33].
• As blockade of phospholipase A2 prevents the induction of long-term potentiation (LTP), inhibition of glutamate uptake by arachidonic acid may contribute to the increase of synaptic gain that occurs in LTP [34].
• Our results indicate that the learning deficits associated with NF1 may be caused by excessive Ras activity, which leads to impairments in long-term potentiation caused by increased GABA-mediated inhibition [35].

Gene context of Long-Term Potentiation

• Activation of the N-methyl-D-aspartate (NMDA) receptor is important for certain forms of activity-dependent synaptic plasticity, such as long-term potentiation (reviewed in ref. 1), and the patterning of connections during development of the visual system (reviewed in refs 2, 3) [36].
• Here we show that targeted disruption of the mouse epsilon 1 subunit gene resulted in significant reduction of the NMDA receptor channel current and long-term potentiation at the hippocampal CA1 synapses [37].
• Recently MAPK activation in post-mitotic cells has been implicated in hippocampal long-term potentiation (LTP), a potential cellular mechanism of learning and memory [38].
• Roles of NMDA NR2B subtype receptor in prefrontal long-term potentiation and contextual fear memory [39].
• Using region-specific and inducible transgenic mice, we show that transiently increased p25 expression in the hippocampus enhanced long-term potentiation (LTP) and facilitated hippocampus-dependent memory [40].

Analytical, diagnostic and therapeutic context of Long-Term Potentiation

• Indeed, specific antagonists of NMDA receptors effectively block spatial learning, long-term potentiation and some animal models of chronic epilepsy [41].
• Cerebral microinjection of cell medium containing these oligomers and abundant Abeta monomers but no amyloid fibrils markedly inhibited hippocampal long-term potentiation (LTP) in rats in vivo [42].
• We demonstrated enhanced presynaptic function during long-term potentiation (LTP) induced either chemically (with tetraethylammonium), or by high-frequency (200-Hz) electrical stimulation [43].
• Glutamate iontophoresis induces long-term potentiation in the absence of evoked presynaptic activity [44].
• Intraperitoneal injections of the drug markedly increased the degree and duration of long-term potentiation; similar results were obtained with an analogue of 1-(1,3-benzodioxol-5-ylcarbonyl)piperidine that was also found to improve retention of memory in a radial maze task and in an odor-matching problem [45].

References