Nitric Oxide Acts Directly in the Presynaptic Neuron to Produce Long-Term Potentiationin Cultured Hippocampal Neurons

Arancio, Ottavio; Kiebler, Michael; Lee, C. Justin; Lev‐Ram, Varda; Tsien, Roger Y.; Kandel, Eric R.; Hawkins, Robert D.

doi:10.1016/s0092-8674(00)81797-3

Cited by 342 publications

(240 citation statements)

References 28 publications

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“…Candidate molecules fulfilling the criteria of a retrograde messenger are arachidonic acid, nitric oxide (NO), and carbon monoxide. An involvement of NO in the generation of LTP has been shown for the hippocampus (Zhuo et al, 1993;O'Dell et al, 1994;Arancio et al, 1996) as well as the neocortex (Haul et al, 1999;Volgushev et al, 2000). Mediated by a retrograde messenger, presynaptic LTP should result from an enhanced release of neurotransmitter.…”

Section: Discussionmentioning

confidence: 98%

Neocortical Long-Term Potentiation and Long-Term Depression: Site of Expression Investigated by Infrared-Guided Laser Stimulation

2002

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The synaptic site of expression of long-term potentiation (LTP) and long-term depression (LTD) is still a matter of debate. To address the question of presynaptic versus postsynaptic expression of neocortical LTP and LTD in a direct approach, we measured the glutamate sensitivity of apical dendrites of layer 5 pyramidal neurons during LTP and LTD. We used infraredguided laser stimulation to release glutamate from its "caged" form with high spatial and temporal resolution. Responses to photolytically released glutamate and synaptically evoked EPSPs were recorded with patch-clamp pipettes from the neuronal somata. LTP and LTD could be induced by electrical stimulation at the same synapses in succession. The NMDA receptor-dependent LTD was accompanied by a decrease in the dendritic glutamate sensitivity, suggesting a postsynaptic expression of neocortical LTD. In contrast, LTP was never accompanied by a change in the dendritic glutamate sensitivity. A possible explanation for this finding is a presynaptic expression of neocortical LTP. Another set of experiments corroborated these results: Photolytic application of glutamate with a frequency of 5 Hz caused a long-lasting Ca 2ϩ and NMDA receptor-dependent decrease in the dendritic glutamate sensitivity. In contrast, LTP of dendritic glutamate sensitivity was never induced by photostimulation, despite several experimental modifications to prevent washout of the induction mechanism and to induce a stronger postsynaptic Ca 2ϩ influx. In conclusion, our findings provide strong evidence for a postsynaptic expression of neocortical LTD and favor a primarily presynaptic locus of neocortical LTP. Key words: caged compounds; expression site; LTP; LTD; neocortex; photostimulationLong-term potentiation (LTP) and long-term depression (LTD) of glutamatergic synapses are considered cellular correlates for learning and memory. The molecular mechanisms that underlie the induction and expression of LTP and LTD have been investigated extensively, primarily in the hippocampus. Most of the available evidence speaks in favor of a postsynaptic induction of LTP and LTD by a rise in the intracellular Ca 2ϩ concentration. However, the synaptic site of expression of LTP and LTD is still a matter of debate.Evidence for a postsynaptic expression of LTP and LTD is provided by several observations. (1) The amplitude of miniature EPSCs (mEPSCs) is increased (decreased) during LTP (LTD) (Manabe et al., 1992;Oliet et al., 1996). (2) Hippocampal LTP (LTD) is accompanied by a higher (lower) sensitivity of the postsynaptic membrane for exogenously applied agonists (Davies et al., 1989;Kandler et al., 1998). (3) A synaptic insertion (redistribution) of AMPA receptors occurs after the induction of LTP (LTD) (Liao et al

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Section: Discussionmentioning

confidence: 98%

Neocortical Long-Term Potentiation and Long-Term Depression: Site of Expression Investigated by Infrared-Guided Laser Stimulation

2002

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“…This is required because it is well established that NMDAR-dependent LTP and LTD are triggered in the postsynaptic cell. Indeed, during the debate about the locus of expression for LTP (and LTD), there was much discussion about the possible identity of so-called retrograde messengers, the substances that might be released from postsynaptic cells following appropriate activation of NMDARs and modify presynaptic function (Arancio et al 1996; but see Williams et al 1993).…”

Section: Expression Mechanismmentioning

confidence: 99%

NMDA Receptor-Dependent Long-Term Potentiation and Long-Term Depression (LTP/LTD)

Lüscher¹,

Malenka²

2012

Cold Spring Harbor Perspectives in Biology

815

647

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Long-term potentiation and long-term depression (LTP/LTD) can be elicited by activating N-methyl-D-aspartate (NMDA)-type glutamate receptors, typically by the coincident activity of pre-and postsynaptic neurons. The early phases of expression are mediated by a redistribution of AMPA-type glutamate receptors: More receptors are added to potentiate the synapse or receptors are removed to weaken synapses. With time, structural changes become apparent, which in general require the synthesis of new proteins. The investigation of the molecular and cellular mechanisms underlying these forms of synaptic plasticity has received much attention, because NMDA receptor-dependent LTP and LTD may constitute cellular substrates of learning and memory.L ong-term synaptic plasticity is a generic term that applies to a long-lasting experience-dependent change in the efficacy of synaptic transmission. Here we will focus on N-methyl-D-aspartate (NMDA) receptor-dependent synaptic potentiation (LTP) and depression (LTD), two forms of activity-dependent long-term changes in synaptic efficacy that have been extensively studied. Because both LTP and LTD are believed to represent cellular correlates of learning and memory, they have attracted considerable interest. In this article we will focus on the molecular and cellular mechanisms associated with LTP and LTD. As for other forms of long-term synaptic plasticity, a characterization of LTP and LTD involves describing the molecular mechanisms that are required to elicit the change (induction), followed by an investigation of the mechanism of expression (hours) and maintenance (days). The best-characterized form of NMDA receptor (NMDAR)-dependent LTP occurs between CA3 and CA1 pyramidal neurons of the hippocampus (Fig. 1). Throughout the chapter we will mostly refer to this specific form of LTP. At these CA3-CA1 Schaffer collateral synapses, the loci of both induction and expression are situated in the postsynaptic neuron. AMPA-TYPE AND NMDA-TYPE GLUTAMATE RECEPTORSAfter exocytotic release of the content of the synaptic vesicle from the presynaptic specialization (see Castillo 2012), the neurotransmitter

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Section: Possible Cooperative Effects Of Bdnf and No In In Vitro Condmentioning

confidence: 99%

“…NO promotes neurotransmitter release through a cGMP-dependent mechanism (Arancio et al, 1996), and may modulate postsynaptic signaling cascades necessary for the induction of synaptic potentiation (Ko and Kelly, 1999). Interestingly, NO behaves in a manner similar to the bidirectional signaling properties of BDNF (Arancio et al, 1996;Shibuki and Kimura, 1997). Like BDNF that could be elicited by glutamate (Griesbeck et al, 1999), NO release is generally linked to the activation of NMDA receptors, which induces influx of Ca 2+ and consequently activation of NOS (for a review, see Garthwaite and Boulton, 1995).…”

Section: Possible Cooperative Effects Of Bdnf and No In In Vitro Condmentioning

confidence: 99%

Coordinate action of pre- and postsynaptic brain-derived neurotrophic factor is required for AMPAR trafficking and acquisition of in vitro classical conditioning

Keifer

2008

Neuroscience

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Brain-derived neurotrophic factor (BDNF) has been implicated in mechanisms of synaptic plasticity such as long-term potentiation (LTP), but its role in associative learning remains largely unknown. In the present study, we investigated the function of BDNF and its receptor tropomyosin-related kinase B (TrkB) in an in vitro model of classical conditioning. Conditioning resulted in a significant increase in BDNF and phospho (p)-Trk expression. Bath application of antibodies directed against TrkB, but not TrkA or TrkC, abolished acquisition of conditioning, as did a receptor tyrosine kinase inhibitor K252a and an inhibitor of nitric oxide synthase 7-nitroindazole. Significantly, injections of BDNF Ab into the nerve roots of presynaptic axonal projections or postsynaptic motor neurons prevented acquisition of conditioning, suggesting that BDNF is required on both sides of the synapse for modification to occur. The presynaptic proteins synaptophysin and synapsin I were increased upon conditioning or BDNF application. Furthermore, BDNF application alone mimicked conditioning-induced synaptic insertion of GluR1 and GluR4 AMPAR subunits into synapses, which was inhibited by co-application of BDNF and K252a. Data also show that extracellular signalregulated kinase (ERK) was activated in BDNF-treated preparations. We conclude that coordinate pre-and postsynaptic actions of BDNF are required for acquisition of in vitro classical conditioning.

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Nitric Oxide Acts Directly in the Presynaptic Neuron to Produce Long-Term Potentiationin Cultured Hippocampal Neurons

Cited by 342 publications

References 28 publications

Neocortical Long-Term Potentiation and Long-Term Depression: Site of Expression Investigated by Infrared-Guided Laser Stimulation

Neocortical Long-Term Potentiation and Long-Term Depression: Site of Expression Investigated by Infrared-Guided Laser Stimulation

NMDA Receptor-Dependent Long-Term Potentiation and Long-Term Depression (LTP/LTD)

Coordinate action of pre- and postsynaptic brain-derived neurotrophic factor is required for AMPAR trafficking and acquisition of in vitro classical conditioning

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