An evaluation of the nitric oxide/cGMP/cGMP-dependent protein kinase cascade in the induction of cerebellar long-term depression in culture

Linden, DJ; Dawson, T. Renee; Dawson, VL

doi:10.1523/jneurosci.15-07-05098.1995

Cited by 192 publications

(77 citation statements)

References 37 publications

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“…However, these studies indicating a role for NO in hippocampal long-term potentiation Madison, 1991, 1994;Zhuo et al, 1994a,b) and hippocampal long-term depression (LTD) (Son et al, 1998) remain controversial (Selig et al, 1996). Similarly, it has been suggested that NO is critically involved in cerebellar LTD (Hartell, 1994(Hartell, , 2001Lev-Ram et al, 1995Boxall and Garthwaite, 1996), although this remains in debate (Linden et al, 1995). The present study proposes an alternative role for NO in influencing neural activity.…”

Section: Discussionmentioning

confidence: 99%

Persistent Changes in Spontaneous Firing of Purkinje Neurons Triggered by the Nitric Oxide Signaling Cascade

Smith

Otis

2003

J. Neurosci.

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Many types of neurons fire spontaneously because of the activity of pacemaking ion channels. Although endogenous firing can serve as a persistent signal to downstream targets, little attention has been paid to factors that might modulate such intrinsic electrical activity. We tested for modulation of spontaneous firing of Purkinje neurons in cerebellar slices under conditions in which principal synaptic inputs were blocked. Loose-patch recordings from single neurons show that sustained (Ͼ40 min) increases in the spontaneous firing rate can be triggered by activation of the nitric oxide-cGMP signaling pathway. Inhibitors of soluble guanylate cyclase and protein kinase G block this modulation. Increases in firing rate are also observed after stimulation of parallel fibers but not in response to basket cell activity. These findings elucidate a novel role for the nitric oxide-cGMP signaling cascade in the brain. This mechanism could permit long-term adjustments in the baseline firing rate of endogenously active neurons in response to changes in afferent activity.

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Section: Discussionmentioning

confidence: 99%

Persistent Changes in Spontaneous Firing of Purkinje Neurons Triggered by the Nitric Oxide Signaling Cascade

Smith

Otis

2003

J. Neurosci.

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“…Cold Spring Harbor Laboratory Press on May 10, 2018 -Published by learnmem.cshlp.org Downloaded from receptors in response to paired glutamate application and depolarization regardless of whether or not the mice had nNOS (Linden et al 1995). It remains tmclear how and why cultured PCs should develop or unmask an independent biochemical cascade to respond to conjunctive extracellular and intracellular stimulation.…”

Section: Discussionmentioning

confidence: 99%

“…The only previous test of nNOS deletion on cerebellar neurons was by Linden et al (1995), who cultured PCs from embryonic knockout mice and found no deficit in their ability to desensitize in response to simultaneous glutamate application and depolarization. This result confirmed their extensive previous data (including the lack of effect of NO donors or NOS inhibitors) showing that NO is not essential for LTD in cultured PCs (Linden and Connor 1992).…”

Section: Introductionmentioning

confidence: 99%

Absence of cerebellar long-term depression in mice lacking neuronal nitric oxide synthase.

Lev‐Ram

Nebyelul²,

Ellisman³

et al. 1997

Learn. Mem.

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IntroductionExtensive pharmacological evidence suggests that nitric oxide (NO) is a crucial transmitter for cerebellar long-term depression (LTD), a long-lasting decrease in efficacy of the synapses from parallel fibers onto Purkinje neurons, triggered by coincident presynaptic activity and postsynaptic depolarization. We now show that LTD cannot be induced in Purkinje neurons under whole-cell patch clamp in cerebellar slices from young adult mice genetically lacking neuronal nitric oxide synthase (nNOS). This genetic evidence confirms the essentiality of NO and nNOS for LTD in young adult rodents. Surprisingly, LTD in cells from nNOS knockout mice cannot be rescued by photolytic uncaging of NO and cGMP inside Purkinje neurons, although such stimuli circumvent acute pharmacological inhibition of nNOS and soluble guanylate cyclase in normal rodents. Also slices from knockout mice show no deficit in cGMP elevation in response to exogenous NO. Therefore, prolonged absence of nNOS allows atrophy of the signaling pathway downstream of cGMP.

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“…Studies in intact heart cells have yielded results consistent with a role for endogenous cADPR in the regulation of excitation-contraction coupling. In guinea pig cardiac myocytes stimulated to fire action potentials, Ca 2ϩ transients and contractions are enhanced by intracellular applications of cADPR (12) and reduced by antagonists of cADPR, 8-amino-cADPR and 8-bromo-cADPR (12)(13)(14)(15)(16)(17). These observations are consistent with endogenous cADPR, acting to enhance the Ca 2ϩ sensitivity of CICR, an action that may be antagonized by 8-amino-cADPR and 8-bromo-cADPR.…”

Section: Oscillations Of Camentioning

confidence: 99%

An Antagonist of cADP-ribose Inhibits Arrhythmogenic Oscillations of Intracellular Ca2+ In Heart Cells

Rakovic

Cui

Iino

et al. 1999

Journal of Biological Chemistry

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Oscillations of Ca2؉ in heart cells are a major underlying cause of important cardiac arrhythmias, and it is known that Ca 2؉ -induced release of Ca 2؉ from intracellular stores (the sarcoplasmic reticulum) is fundamental to the generation of such oscillations. There is now evidence that cADP-ribose may be an endogenous regulator of the Ca 2؉ release channel of the sarcoplasmic reticulum (the ryanodine receptor), raising the possibility that cADP-ribose may influence arrhythmogenic mechanisms in the heart. 8-Amino-cADP-ribose, an antagonist of cADP-ribose, suppressed oscillatory activity associated with overloading of intracellular Ca 2؉ stores in cardiac myocytes exposed to high doses of the ␤-adrenoreceptor agonist isoproterenol or the Na

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An evaluation of the nitric oxide/cGMP/cGMP-dependent protein kinase cascade in the induction of cerebellar long-term depression in culture

Cited by 192 publications

References 37 publications

Persistent Changes in Spontaneous Firing of Purkinje Neurons Triggered by the Nitric Oxide Signaling Cascade

Persistent Changes in Spontaneous Firing of Purkinje Neurons Triggered by the Nitric Oxide Signaling Cascade

Absence of cerebellar long-term depression in mice lacking neuronal nitric oxide synthase.

An Antagonist of cADP-ribose Inhibits Arrhythmogenic Oscillations of Intracellular Ca2+ In Heart Cells

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