Nitric Oxide Facilitates Long-Term Potentiation, But Not Long-Term Depression

Malen, Peter; Chapman, Paul F.

doi:10.1523/jneurosci.17-07-02645.1997

Cited by 77 publications

(62 citation statements)

References 34 publications

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“…Because the high concentration of L-NAME used in our experiments inhibits the induction of LTP by some protocols (Böhme et al 1991;Haley et al 1992;Ko and Kelly 1999), the results shown in Figure 3B suggest that the inhibition of additional LTP induction at potentiated synapses does not arise from mechanisms that require NO production. Furthermore, the lack of an effect of L-NAME on the amount of LTP induced by the first train of 5-Hz stimulation in these experiments indicates that 5-Hz stimulation induces an NO-independent form of LTP in the CA1 region of the hippocampus (at least during the first 20 min after 5-Hz stimulation), a finding consistent with previous observations that NO is not required for the induction of LTP by some patterns of synaptic stimulation (Gribkoff and Lum-Ragan 1992;Chetkovich et al 1993;Haley et al 1993;Malen and Chapman 1997).…”

Section: A No-dependent Inhibition Of Nmda Receptor Activity Is Not Rsupporting

confidence: 91%

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

Moody¹,

Carlisle²,

O’Dell³

1999

Learn. Mem.

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The induction of long-term potentiation (LTP) and long-term depression (LTD) at excitatory synapses in the hippocampus can be strongly modulated by patterns of synaptic stimulation that otherwise have no direct effect on synaptic strength. Likewise, patterns of synaptic stimulation that induce LTP or LTD not only modify synaptic strength but can also induce lasting changes that regulate how synapses will respond to subsequent trains of stimulation. Collectively known as metaplasticity, these activity-dependent processes that regulate LTP and LTD induction allow the recent history of synaptic activity to influence the induction of activity-dependent changes in synaptic strength and may thus have an important role in information storage during memory formation. To explore the cellular and molecular mechanisms underlying metaplasticity, we investigated the role of metaplasticity in the induction of LTP by -frequency (5-Hz) synaptic stimulation in the hippocampal CA1 region. Our results show that brief trains of -frequency stimulation not only induce LTP but also activate a process that inhibits the induction of additional LTP at potentiated synapses. Unlike other forms of metaplasticity, the inhibition of LTP induction at potentiated synapses does not appear to arise from activity-dependent changes in NMDA receptor function, does not require nitric oxide signaling, and is strongly modulated by ␤-adrenergic receptor activation. Together with previous findings, our results indicate that mechanistically distinct forms of metaplasticity regulate LTP induction and suggest that one way modulatory transmitters may act to regulate synaptic plasticity is by modulating metaplasticity.

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Section: A No-dependent Inhibition Of Nmda Receptor Activity Is Not Rsupporting

confidence: 91%

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

Moody¹,

Carlisle²,

O’Dell³

1999

Learn. Mem.

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“…Both GC inhibitor ODQ and PKG inhibitor KT5823 inhibited the enhancement of LTP by YC-1, suggesting that the NO-cGMP-PKG pathway mediated the influence of YC-1 on synaptic plasticity. It has been demonstrated that NO may be particularly important in regulating the threshold of LTP induction, because NOS inhibitors blocked LTP induced by weak, but not strong, afferent stimulation in CA1 (O'Dell et al, 1994;Malen and Chapman, 1997;Zhuo et al, 1998;Lu et al, 1999). Here we showed that YC-1 induced LTP at weak tetanus by amplifying the signal transduction of NO, indicating that YC-1 also lowers the threshold for LTP induction.…”

Section: Discussionsupporting

confidence: 55%

Enhancement of Long-Term Potentiation by a Potent Nitric Oxide-Guanylyl Cyclase Activator, 3-(5-Hydroxymethyl-2-furyl)-1-benzyl-indazole

Chien

Liang²,

Teng³

et al. 2003

Mol Pharmacol

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Nitric oxide (NO) is known to affect synaptic plasticity in various regions of the brain via the cGMP-cGMP-dependent protein kinase (PKG) pathway. We found that a novel compound 3-(5-hydroxymethyl-2-furyl)-1-benzyl-indazole (YC-1), a drug known to modulate the response of soluble guanylyl cyclase to NO, greatly potentiates long-term potentiation (LTP). This compound markedly enhanced the induction of LTP in rat hippocampal and amygdala slices by weak tetanic stimulation. The potentiation of LTP by YC-1 was greatly reduced by NO synthase inhibitor N G -nitro-L-arginine-methylester, guanylyl cyclase inhibitor 1 H-[1,2,4]-oxadiazolo(4,3-a)-quinoxalin-1-one, and PKG inhibitor (9S,10R,12R)-2,3,9,10,11,12, hexahydro-10-methoxy-2,9-dimethyl-1-ox0 -9.12-epoxy-1H-diindolo[1,2,3-fg:3Ј,2Ј,1Ј-kl]pyrrolo[3,4-I][1,6]benzodiazocine-10-carboxylic acid methyl ester (KT5823). In addition, mitogen-activated protein kinase kinase inhibitor 2Ј-amino-3Ј-methoxyflavone (PD98059) also markedly inhibited LTP potentiating action of YC-1. Intracellular increase of Ca 2ϩ concentration derived from N-methyl-D-aspartate and glutamate metabotropic receptors contributes to the potentiating action of YC-1. Concurrent perfusion of YC-1 and NO donor sodium nitroprusside for a short time period resulted in the induction of LTP by stimuli at a frequency as low as 0.02 Hz. Incubation of unstimulated hippocampal slices with YC-1 plus nitroprusside increased the immunofluorescence of phosphoextracellular signal-regulated kinase (ERK) and phospho-cAMP response element binding protein (CREB). Furthermore, the Western blot shows that the phosphorylation of ERKs 1 and 2 and CREB of unstimulated hippocampal slices was increased by YC-1 plus nitroprusside, which was inhibited by KT5823. The NO-cGMP-PKG-ERK signaling pathway thus plays important role in the potentiation of LTP by YC-1.Learning and memory are two of the most intensively studied subjects in neuroscience. Various approaches have been used to understand the underlying cellular and molecular mechanisms. Long-term potentiation (LTP) has been identified as a potential synaptic mechanism in several regions of the brain involved in learning and memory (Abel and Lattal, 2001;Schafe et al., 2001). Schaffer collateral inputs to pyramidal neurons in the hippocampus CA1 region exhibit a form of LTP that critically depends on N-methyl-D-aspartate (NMDA) receptor-mediated Ca 2ϩ influx into the postsynaptic cell (Tsien et al., 1996). It has been suggested that nitric oxide (NO), generated postsynaptically by Ca 2ϩ -calmodulindependent NO synthase (NOS), acts as a retrograde messenger (Son et al., 1996;Wilson et al., 1997). A major target of NO is soluble guanylyl cyclase (sGC), which generates the intracellular second messenger cGMP. Consistent with a functional role of cGMP in the expression of LTP, sGC inhibitors suppress LTP (Zhuo et al., 1994), and membrane-permeable dibutyryl-cGMP partially reverses reduction of LTP by an NOS inhibitor (Haley et al., 1992). It is well known that GMP regulates th...

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“…Administration of exogenous NO paired with a weak tetanic stimulation of afferent fibers generates an NMDA receptorindependent LTP (Zhuo et al, 1993;Malen and Chapman, 1997;Bon and Garthwaite, 2003), a result that fulfils a key prediction of the retrograde messenger hypothesis. Surprisingly, however, for exogenous NO to potentiate synaptic transmission in this way, a source of endogenous NO was needed, both before and after the pairing protocol (Bon and Garthwaite, 2003).…”

Section: Introductionsupporting

confidence: 54%

Tonic and Phasic Nitric Oxide Signals in Hippocampal Long-Term Potentiation

Hopper¹,

Garthwaite²

2006

J. Neurosci.

198

150

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Nitric oxide (NO) participates in long-term potentiation (LTP) and other forms of synaptic plasticity in many different brain areas but where it comes from and how it acts remain controversial. Using rat and mouse hippocampal slices, we tested the hypothesis that tonic and phasic NO signals are needed and that they derive from different NO synthase isoforms. NMDA increased NO production in a manner that was potently inhibited by three different neuronal NO synthase (nNOS) inhibitors. Tonic NO could be monitored after sensitizing guanylyl cyclase-coupled NO receptors, allowing the very low ambient NO concentrations to be detected by cGMP measurement. The levels were unaffected by inhibition of NMDA receptors, nNOS, or the inducible NO synthase (iNOS). iNOS was also undetectable in protein or activity assays. Tonic NO was susceptible to agents inhibiting endothelial NO synthase (eNOS) and was missing in eNOS knock-out mice. The eNOS knock-outs exhibited a deficiency in LTP resembling that seen in wild-types treated with a NO synthase inhibitor. LTP in the knock-outs could be fully restored by supplying a low level of NO exogenously. Inhibition of nNOS also caused a major loss of LTP, particularly of late-LTP. Again, exogenous NO could compensate, but higher concentrations were needed compared with those restoring LTP in the eNOS knock-outs. It is concluded that tonic and phasic NO signals are both required for hippocampal LTP and the two are generated, respectively, by eNOS and nNOS, the former in blood vessels and the latter in neurons.

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Nitric Oxide Facilitates Long-Term Potentiation, But Not Long-Term Depression

Cited by 77 publications

References 34 publications

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

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

Enhancement of Long-Term Potentiation by a Potent Nitric Oxide-Guanylyl Cyclase Activator, 3-(5-Hydroxymethyl-2-furyl)-1-benzyl-indazole

Tonic and Phasic Nitric Oxide Signals in Hippocampal Long-Term Potentiation

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