scholarly journals Nitric Oxide Regulates GluA2-Lacking AMPAR Contribution to Synaptic Transmission of CA1 Apical but Not Basal Dendrites

2021 ◽  
Vol 13 ◽  
Author(s):  
Violetta O. Ivanova ◽  
Pavel M. Balaban ◽  
Natalia V. Bal
Keyword(s):  
Nitric Oxide ◽  
Synaptic Transmission ◽  
Ampa Receptors ◽  
Soluble Guanylate Cyclase ◽  
Long Term Potentiation ◽  
Stratum Radiatum ◽  
Stratum Oriens ◽  
Basal Dendrites ◽  
Local Circuits ◽  
Apical Dendrites

The mechanisms of synaptic plasticity differ in distinct local circuits. In the CA1 region of the hippocampus, the mechanisms of long-term potentiation (LTP) at apical dendrites in stratum radiatum and basal dendrites in stratum oriens involve different molecular cascades. For instance, participation of nitric oxide in LTP induction was shown to be necessary only for apical dendrites. This phenomenon may play a key role in information processing in CA1, and one of the reasons for this difference may be differing synaptic characteristics in these regions. Here, we compared the synaptic responses to stimulation of apical and basal dendrites of CA1 pyramidal neurons and found a difference in the current–voltage characteristics of these inputs, which is presumably due to a distinct contribution of GluA2-lacking AMPA receptors to synaptic transmission. In addition, we obtained data that indicate the presence of these receptors in pyramidal dendrites in both stratum radiatum and stratum oriens. We also demonstrated that inhibition of NO synthase reduced the contribution of GluA2-lacking AMPA receptors at apical but not basal dendrites, and inhibition of soluble guanylate cyclase did not affect this phenomenon.

scholarly journals Evidence of calcium-permeable AMPA receptors in dendritic spines of CA1 pyramidal neurons

2014 ◽  
Vol 112 (2) ◽  
pp. 263-275 ◽  
Author(s):  
Hayley A. Mattison ◽  
Ashish A. Bagal ◽  
Michael Mohammadi ◽  
Nisha S. Pulimood ◽  
Christian G. Reich ◽  
...  
Keyword(s):  
Dendritic Spines ◽  
Ampa Receptors ◽  
Pyramidal Neurons ◽  
Calcium Influx ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Stratum Radiatum ◽  
Acute Hippocampal Slices ◽  
Cultured Slices ◽  
Apical Dendrites

GluA2-lacking, calcium-permeable α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors (AMPARs) have unique properties, but their presence at excitatory synapses in pyramidal cells is controversial. We have tested certain predictions of the model that such receptors are present in CA1 cells and show here that the polyamine spermine, but not philanthotoxin, causes use-dependent inhibition of synaptically evoked excitatory responses in stratum radiatum, but not s. oriens, in cultured and acute hippocampal slices. Stimulation of single dendritic spines by photolytic release of caged glutamate induced an N-methyl-d-aspartate receptor-independent, use- and spermine-sensitive calcium influx only at apical spines in cultured slices. Bath application of glutamate also triggered a spermine-sensitive influx of cobalt into CA1 cell dendrites in s. radiatum. Responses of single apical, but not basal, spines to photostimulation displayed prominent paired-pulse facilitation (PPF) consistent with use-dependent relief of cytoplasmic polyamine block. Responses at apical dendrites were diminished, and PPF was increased, by spermine. Intracellular application of pep2m, which inhibits recycling of GluA2-containing AMPARs, reduced apical spine responses and increased PPF. We conclude that some calcium-permeable, polyamine-sensitive AMPARs, perhaps lacking GluA2 subunits, are present at synapses on apical dendrites of CA1 pyramidal cells, which may allow distinct forms of synaptic plasticity and computation at different sets of excitatory inputs.

scholarly journals Opposing actions of nitric oxide on synaptic inputs of identified interneurones in the central nervous system of the crayfish

2001 ◽  
Vol 204 (7) ◽  
pp. 1319-1332 ◽  
Author(s):  
H. Aonuma ◽  
P.L. Newland
Keyword(s):  
Nitric Oxide ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Sensory Nerve ◽  
Signal Transduction Pathway ◽  
Response Class ◽  
No Donor ◽  
Synaptic Inputs ◽  
Class 1 ◽  
Local Circuits

Little is known of the action of nitric oxide (NO) at the synaptic level on identified interneurones in local circuits that process mechanosensory signals. Here, we examine the action of NO in the terminal abdominal ganglion of the crayfish Pacifastacus leniusculus, where it has modulatory effects on the synaptic inputs of 17 identified ascending interneurones mediated by electrical stimulation of a sensory nerve. To analyse the role of NO in the processing of sensory signals, we bath-applied the NO donor SNAP, the NO scavenger PTIO, the nitric oxide synthase (NOS) inhibitor l-NAME, the NOS substrate l-arginine, a cyclic GMP (cGMP) analogue, 8-Br-cGMP, and the soluble guanylate cyclase (sGC) inhibitor ODQ. The effects of these chemicals on the synaptic inputs of the interneurones could be divided into two distinct classes. The NO donor SNAP enhanced the inputs to one class of interneurone (class 1) and depressed those to another (class 2). Neither the inactive isomer NAP nor degassed SNAP had any effect on the inputs to these same classes of interneurone. The NO scavenger PTIO caused the opposite effects to those of the NO donor SNAP, indicating that endogenous NO may have an action in local circuits. Preventing the synthesis of NO using l-NAME had the opposite effect to that of SNAP on each response class of interneurone. Increasing the synthesis of endogenous NO by applying l-arginine led to effects on both response classes of interneurone similar to those of SNAP. Taken together, these results suggested that NO was the active component in mediating the changes in amplitude of the excitatory postsynaptic potentials. Finally, the effects of 8-Br-cGMP were similar to those of the NO donor, indicating the possible involvement of a NO-sensitive guanylate cyclase. This was confirmed by preventing the synthesis of cGMP by sGC using ODQ, which caused the opposite effects to those of 8-Br-cGMP on the two response classes of interneurone. The results indicate that a NO-cGMP signal transduction pathway, in which NO regulates transmitter release from mechanosensory afferents onto intersegmental ascending interneurones, is probably present in the local circuits of the crayfish.

scholarly journals Nitric Oxide-Mediated Posttranslational Modifications: Impacts at the Synapse

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Sophie A. Bradley ◽  
Joern R. Steinert
Keyword(s):  
Nitric Oxide ◽  
Synaptic Transmission ◽  
Posttranslational Modifications ◽  
Nitrosative Stress ◽  
Long Term Potentiation ◽  
No Production ◽  
Normal Brain ◽  
Calcium Dependent ◽  
Physiological Processes

Nitric oxide (NO) is an important gasotransmitter molecule that is involved in numerous physiological processes throughout the nervous system. In addition to its involvement in physiological plasticity processes (long-term potentiation, LTP; long-term depression, LTD) which can include NMDAR-mediated calcium-dependent activation of neuronal nitric oxide synthase (nNOS), new insights into physiological and pathological consequences of nitrergic signalling have recently emerged. In addition to the canonical cGMP-mediated signalling, NO is also implicated in numerous pathways involving posttranslational modifications. In this review we discuss the multiple effects of S-nitrosylation and 3-nitrotyrosination on proteins with potential modulation of function but limit the analyses to signalling involved in synaptic transmission and vesicular release. Here, crucial proteins which mediate synaptic transmission can undergo posttranslational modifications with either pre- or postsynaptic origin. During normal brain function, both pathways serve as important cellular signalling cascades that modulate a diverse array of physiological processes, including synaptic plasticity, transcriptional activity, and neuronal survival. In contrast, evidence suggests that aging and disease can induce nitrosative stressviaexcessive NO production. Consequently, uncontrolled S-nitrosylation/3-nitrotyrosination can occur and represent pathological features that contribute to the onset and progression of various neurodegenerative diseases, including Parkinson’s, Alzheimer’s, and Huntington’s.

scholarly journals Mechanisms of heterosynaptic metaplasticity

2014 ◽  
Vol 369 (1633) ◽  
pp. 20130148 ◽  
Author(s):  
Sarah R. Hulme ◽  
Owen D. Jones ◽  
Clarke R. Raymond ◽  
Pankaj Sah ◽  
Wickliffe C. Abraham
Keyword(s):  
Synaptic Plasticity ◽  
Long Range ◽  
Intercellular Communication ◽  
Atp Hydrolysis ◽  
Long Term Potentiation ◽  
Stratum Radiatum ◽  
Signalling Pathways ◽  
Stratum Oriens ◽  
Term Potentiation

Synaptic plasticity is fundamental to the neural processes underlying learning and memory. Interestingly, synaptic plasticity itself can be dynamically regulated by prior activity, in a process termed ‘metaplasticity’, which can be expressed both homosynaptically and heterosynaptically. Here, we focus on heterosynaptic metaplasticity, particularly long-range interactions between synapses spread across dendritic compartments, and review evidence for intra cellular versus inter cellular signalling pathways leading to this effect. Of particular interest is our previously reported finding that priming stimulation in stratum oriens of area CA1 in the hippocampal slice heterosynaptically inhibits subsequent long-term potentiation and facilitates long-term depression in stratum radiatum. As we have excluded the most likely intracellular signalling pathways that might mediate this long-range heterosynaptic effect, we consider the hypothesis that intercellular communication may be critically involved. This hypothesis is supported by the finding that extracellular ATP hydrolysis, and activation of adenosine A2 receptors are required to induce the metaplastic state. Moreover, delivery of the priming stimulation in stratum oriens elicited astrocytic calcium responses in stratum radiatum. Both the astrocytic responses and the metaplasticity were blocked by gap junction inhibitors. Taken together, these findings support a novel intercellular communication system, possibly involving astrocytes, being required for this type of heterosynaptic metaplasticity.

scholarly journals Associative spike timing-dependent potentiation of the basal dendritic excitatory synapses in the hippocampus in vivo

2016 ◽  
Vol 115 (6) ◽  
pp. 3264-3274 ◽  
Author(s):  
Thomas K. Fung ◽  
Clayton S. Law ◽  
L. Stan Leung
Keyword(s):  
Current Source ◽  
Long Term Potentiation ◽  
Spike Timing ◽  
Stratum Radiatum ◽  
Adult Rats ◽  
Synaptic Excitation ◽  
Stratum Oriens ◽  
Term Potentiation

Spike timing-dependent plasticity in the hippocampus has rarely been studied in vivo. Using extracellular potential and current source density analysis in urethane-anesthetized adult rats, we studied synaptic plasticity at the basal dendritic excitatory synapse in CA1 after excitation-spike (ES) pairing; E was a weak basal dendritic excitation evoked by stratum oriens stimulation, and S was a population spike evoked by stratum radiatum apical dendritic excitation. We hypothesize that positive ES pairing—generating synaptic excitation before a spike—results in long-term potentiation (LTP) while negative ES pairing results in long-term depression (LTD). Pairing (50 pairs at 5 Hz) at ES intervals of −10 to 0 ms resulted in significant input-specific LTP of the basal dendritic excitatory sink, lasting 60–120 min. Pairing at +10- to +20-ms ES intervals, or unpaired 5-Hz stimulation, did not induce significant basal dendritic or apical dendritic LTP or LTD. No basal dendritic LTD was found after stimulation of stratum oriens with 200 pairs of high-intensity pulses at 25-ms interval. Pairing-induced LTP was abolished by pretreatment with an N-methyl-d-aspartate receptor antagonist, 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), which also reduced spike bursting during 5-Hz pairing. Pairing at 0.5 Hz did not induce spike bursts or basal dendritic LTP. In conclusion, ES pairing at 5 Hz resulted in input-specific basal dendritic LTP at ES intervals of −10 ms to 0 ms but no LTD at ES intervals of −20 to +20 ms. Associative LTP likely occurred because of theta-rhythmic coincidence of subthreshold excitation with a backpropagated spike burst, which are conditions that can occur naturally in the hippocampus.

scholarly journals Enhancing Plasticity Mechanisms in the Mouse Motor Cortex by Anodal Transcranial Direct-Current Stimulation: The Contribution of Nitric Oxide Signaling

2019 ◽  
Vol 30 (5) ◽  
pp. 2972-2985 ◽  
Author(s):  
Saviana Antonella Barbati ◽  
Sara Cocco ◽  
Valentina Longo ◽  
Matteo Spinelli ◽  
Katia Gironi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Motor Cortex ◽  
Synaptic Transmission ◽  
Direct Current ◽  
Transcranial Direct Current Stimulation ◽  
Molecular Mechanisms ◽  
Primary Motor Cortex ◽  
Long Term Potentiation ◽  
Anodal Tdcs ◽  
Direct Current Stimulation

Abstract Consistent body of evidence shows that transcranial direct-current stimulation (tDCS) over the primary motor cortex (M1) facilitates motor learning and promotes recovery after stroke. However, the knowledge of molecular mechanisms behind tDCS effects needs to be deepened for a more rational use of this technique in clinical settings. Here we characterized the effects of anodal tDCS of M1, focusing on its impact on glutamatergic synaptic transmission and plasticity. Mice subjected to tDCS displayed increased long-term potentiation (LTP) and enhanced basal synaptic transmission at layer II/III horizontal connections. They performed better than sham-stimulated mice in the single-pellet reaching task and exhibited increased forelimb strength. Dendritic spine density of layer II/III pyramidal neurons was also increased by tDCS. At molecular level, tDCS enhanced: 1) BDNF expression, 2) phosphorylation of CREB, CaMKII, and GluA1, and 3) S-nitrosylation of GluA1 and HDAC2. Blockade of nitric oxide synthesis by L-NAME prevented the tDCS-induced enhancement of GluA1 phosphorylation at Ser831 and BDNF levels, as well as of miniature excitatory postsynaptic current (mEPSC) frequency, LTP and reaching performance. Collectively, these findings demonstrate that anodal tDCS engages plasticity mechanisms in the M1 and highlight a role for nitric oxide (NO) as a novel mediator of tDCS effects.

Voltage-Controlled Plasticity at GluR2-Deficient Synapses Onto Hippocampal Interneurons

2004 ◽  
Vol 92 (6) ◽  
pp. 3575-3581 ◽  
Author(s):  
Fernanda Laezza ◽  
Raymond Dingledine
Keyword(s):  
Membrane Potential ◽  
Nmda Receptors ◽  
Ampa Receptors ◽  
High Frequency ◽  
Long Term Potentiation ◽  
Receptor Expression ◽  
Stratum Radiatum ◽  
High Frequency Stimulation ◽  
Frequency Stimulation

High-frequency stimulation of pyramidal cell inputs to developing (P9-12) hippocampal stratum radiatum interneurons expressing GluR2-lacking, Ca2+-permeable AMPA receptors produces long-term depression of synaptic transmission, if N-methyl-d-aspartate (NMDA) receptors are blocked. Here we show that these same synapses display a remarkably versatile signal integration if postsynaptic NMDA receptors are activated. At synapses expressing GluR2-deficient AMPA receptors, tetanic stimulation that activates NMDA receptors triggered long-term potentiation or depression (LTP or LTD) depending on membrane potential. LTP was elicited at most synapses when the interneuron was held at –30 mV during the stimulus train but was typically prevented by postsynaptic hyperpolarization to –70 mV, by strong depolarization to 0 mV, by d-2-amino-5-phosphonovaleric acid, or by postsynaptic injection of the Ca2+ chelator bis-( o-aminophenoxy)- N,N,N′,N′-tetraacetic acid. At synapses with predominantly GluR2-containing AMPA receptors, repetitive stimulation did not change synaptic strength regardless of whether NMDA receptors were activated. The interactions among GluR2 expression, NMDA receptor expression, and membrane potential thus confer on hippocampal interneurons a distinctive means for differential decoding of high-frequency inputs, resulting in enhanced or depressed transmission depending on the functional state of the interneuron.

Altered Plasticity in Hippocampal CA1, But Not Dentate Gyrus, Following Long-Term Environmental Enrichment

2010 ◽  
Vol 103 (6) ◽  
pp. 3320-3329 ◽  
Author(s):  
Michael J. Eckert ◽  
David K. Bilkey ◽  
Wickliffe C. Abraham
Keyword(s):  
Synaptic Transmission ◽  
Dentate Gyrus ◽  
Long Term Potentiation ◽  
Enriched Environment ◽  
Cognitive Improvement ◽  
Stratum Oriens ◽  
Hippocampal Ca1

Exposure to an enriched environment can improve cognitive functioning in normal animals as well as in animal models of neurological disease and impairment. However, the physiological processes that mediate these changes are poorly understood. Previously we and others have found changes in hippocampal synaptic transmission and plasticity after 2–4 wk of enrichment although others have not observed effects. To determine whether long-term enrichment produces more robust changes, we housed rats continuously in an enriched environment for a minimum of 3 mo and then tested for effects on hippocampal physiology in vitro and in vivo. Enriched housing improved spatial learning compared with social and isolated housing, but surprisingly this was not accompanied by changes in basal synaptic transmission in either CA1 or the dentate gyrus as measured either in vitro or in vivo. This lack of change may reflect the operation of homeostatic mechanisms that keep global synaptic weights within a narrow range. In tests of synaptic plasticity, the induction of long-term potentiation was not changed in either CA1 or the dentate gyrus. However, in CA1 of enriched rats, there was less long-term depression in stratum radiatum, less depotentiation in stratum oriens, and altered paired-pulse inhibition of population spikes evoked in stratum oriens. These effects suggest that there are altered synaptic and network dynamics in hippocampal CA1 that contribute to the enrichment-related cognitive improvement.

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