Suppression of the induction of long‐term depression by carbon monoxide in rat cerebellar slices

Shibuki, Katsuei; Kimura, Satoshi; Wakatsuki, Hidemitsu

doi:10.1046/j.0953-816x.2000.01413.x

“…This result suggests a tight coupling between NMDARs and NOS that may minimize crosstalk between the Ca 2+ entry involved in transmitter release and the Ca 2+ signaling implicated in plasticity induction through the NMDAR–NOS system. These results are also consistent with the involvement of NO in PF-PC LTP described in this study, previous in vitro studies reporting a role of NO in LTD in adult rodents ( 57 , 58 ), and visuo-motor behavior studies showing a learning impairment in NOS knockout mice ( 59 ).…”

Section: Discussionsupporting

confidence: 93%

NMDARs in granule cells contribute to parallel fiber–Purkinje cell synaptic plasticity and motor learning

Schonewille¹,

Girasole

²

,

Rostaing

³

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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Long-term synaptic plasticity is believed to be the cellular substrate of learning and memory. Synaptic plasticity rules are defined by the specific complement of receptors at the synapse and the associated downstream signaling mechanisms. In young rodents, at the cerebellar synapse between granule cells (GC) and Purkinje cells (PC), bidirectional plasticity is shaped by the balance between transcellular nitric oxide (NO) driven by presynaptic N-methyl-D-aspartate receptor (NMDAR) activation and postsynaptic calcium dynamics. However, the role and the location of NMDAR activation in these pathways is still debated in mature animals. Here, we show in adult rodents that NMDARs are present and functional in presynaptic terminals where their activation triggers NO signaling. In addition, we find that selective genetic deletion of presynaptic, but not postsynaptic, NMDARs prevents synaptic plasticity at parallel fiber-PC (PF-PC) synapses. Consistent with this finding, the selective deletion of GC NMDARs affects adaptation of the vestibulo-ocular reflex. Thus, NMDARs presynaptic to PCs are required for bidirectional synaptic plasticity and cerebellar motor learning.

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“…This result suggests a tight coupling between NMDARs and NOS that may minimize crosstalk between the Ca 2+ entry involved in transmitter release and the Ca 2+ signaling implicated in plasticity induction through the NMDAR-NOS system. These results are also consistent with the involvement of NO in PF-PC LTP described in this study, previous in vitro studies reporting a role of NO in LTD in adult rodents (52,53), and visuomotor behavior studies showing a learning impairment in NOS knockout mice (54).…”

Section: Location Of Presynaptic Nmdars Presynaptic Receptors Are Often Found Within the Active Zonesupporting

confidence: 93%

NMDARs in Granule Cells contribute to parallel fiber - Purkinje cell synaptic plasticity and motor learning

Schonewille

¹

,

Girasole

²

,

Rostaing

³

et al. 2021

Preprint

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Long-term synaptic plasticity is believed to be the cellular substrate of learning and memory. Synaptic plasticity rules are defined by the specific complement of receptors at the synapse and the associated downstream signaling mechanisms. In young rodents, at the cerebellar synapse between granule cells and Purkinje cells, bidirectional plasticity is shaped by the balance between transcellular nitric oxide driven by presynaptic NMDA receptor (NMDAR) activation and postsynaptic calcium dynamics. However, the role and the location of NMDAR activation in these pathways is still debated in mature animals. Here, we show in adult rodents that NMDARs are present and functional in presynaptic terminals where their activation triggers nitric oxide (NO) signaling. In addition, we find that selective genetic deletion of presynaptic, but not postsynaptic, NMDARs prevents synaptic plasticity at parallel fiber-Purkinje cell (PF-PC) synapses. Consistent with this finding, the selective deletion of granule cells NMDARs affects adaptation of the vestibulo-ocular reflex. Thus, NMDARs presynaptic to PCs are required for bidirectional synaptic plasticity and cerebellar motor learning.Significance StatementLearning depends on synaptic plasticity. The signaling mechanisms that control induction of this plasticity determines the learning rules at the specific synapse involved. Moreover, the relationship between the activity patterns of synaptic inputs and the type, direction, and level of plasticity induced may evolve during development. Here, we establish a key link between NMDA receptor activation presynaptic to cerebellar Purkinje cells, downstream signaling, and the ability of adult animals to learn a cerebellar motor task.

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“…3). For instance, CO regulates expression of the neuronal ␣3 isoform of Na ϩ -K ϩ -ATPase in rat cerebellar slices (30,41), participates in induction of long-term potentiation in rat superior cervical ganglion (2) and mediates tonic retrograde upregulation of neurotransmitter release at the frog neuromuscular junction (43). CO also controls the level of resting membrane potential within the gut smooth muscle (14,40,44), and its presence is essential for normal inhibitory neuromuscular transmission in these muscles (16).…”

Section: Discussionmentioning

confidence: 99%

Impairment of diaphragm muscle force and neuromuscular transmission after normothermic cardiopulmonary bypass: effect of low-dose inhaled CO

Ermilov¹,

Pulido

²

,

Atchison

³

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

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Cardiopulmonary bypass (CPB) is associated with significant postoperative morbidity, but its effects on the neuromuscular system are unclear. Recent studies indicate that even relatively short periods of mechanical ventilation result in significant neuromuscular effects. Carbon monoxide (CO) has gained recent attention as therapy to reduce the deleterious effects of CPB. We hypothesized that 1) CPB results in impaired neuromuscular transmission and reduced diaphragm force generation; and 2) CO treatment during CPB will mitigate these effects. In adult male Sprague-Dawley rats, diaphragm muscle-specific force and neuromuscular transmission properties were measured 90 min after weaning from normothermic CPB (1 h). During CPB, either low-dose inhaled CO (250 ppm) or air was administered. The short period of mechanical ventilation used in the present study ( approximately 3 h) did not adversely affect diaphragm muscle contractile properties or neuromuscular transmission. CPB elicited a significant decrease in isometric diaphragm muscle-specific force compared with time-matched, mechanically ventilated rats ( approximately 25% decline in both twitch and tetanic force). Diaphragm muscle fatigability to 40-Hz repetitive stimulation did not change significantly. Neuromuscular transmission failure during repetitive activation was 60 +/- 2% in CPB animals compared with 76 +/- 4% in mechanically ventilated rats (P < 0.05). CO treatment during CPB abrogated the neuromuscular effects of CPB, such that diaphragm isometric twitch force and neuromuscular transmission were no longer significantly different from mechanically ventilated rats. Thus, CPB has important detrimental effects on diaphragm muscle contractility and neuromuscular transmission that are largely mitigated by CO treatment. Further studies are needed to ascertain the underlying mechanisms of CPB-induced neuromuscular dysfunction and to establish the potential role of CO therapy.

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Suppression of the induction of long‐term depression by carbon monoxide in rat cerebellar slices

Cited by 11 publications

References 63 publications

NMDARs in granule cells contribute to parallel fiber–Purkinje cell synaptic plasticity and motor learning

NMDARs in granule cells contribute to parallel fiber–Purkinje cell synaptic plasticity and motor learning

NMDARs in Granule Cells contribute to parallel fiber - Purkinje cell synaptic plasticity and motor learning

Impairment of diaphragm muscle force and neuromuscular transmission after normothermic cardiopulmonary bypass: effect of low-dose inhaled CO

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