Determining the Neurotransmitter Concentration Profile at Active Synapses

Scimemi, Annalisa; Beato, Marco

doi:10.1007/s12035-009-8087-7

Cited by 121 publications

(146 citation statements)

References 145 publications

(208 reference statements)

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“…Because Katsuki et al did not use DCG-IV or assess any other features of short-term plasticity at mossy fiber-CA3 synapses to confirm the pure mossy fiber signals, it is possible that NMDA receptor-dependent potentiation at the CA3 recurrent collaterals was contaminated in their study. While we used 1 ng/mL IL-1β in the current study, it is difficult to determine precise synaptic concentrations under pathological conditions (27). Most investigators consider concentration of IL-1β in picograms per milliliters to be healthy (1, 23,25), and this is essential for sustained LTP expression (25).…”

Section: Resultsmentioning

confidence: 99%

Synapse-specific effects of IL-1β on long-term potentiation in the mouse hippocampus

et al. 2017

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Interleukin-1β (IL-1β) is a key molecule in the inflammatory responses elicited during infection and injury. It exerts local effects on synaptic plasticity by binding to IL-1 receptors that are expressed at high levels in the hippocampus. We examined the effects of IL-1β on synaptic plasticity in different hippocampal regions in acute mouse brain slices by measuring long-term potentiation (LTP). IL-1β (1 ng/mL) was applied for 30 min before LTP was induced with high-frequency stimulation (HFS). LTP was significantly impaired by either IL-1β application to the Schaffer collateral-CA1 synapses or the associational/commissural (A/C) fiber-CA3 synapses, which are both dependent on N-methyl-D-aspartate (NMDA) receptor activation. However, mossy fiber-CA3 LTP, which is expressed presynaptically in an NMDA-independent manner, was not impaired by IL-1β. Our results demonstrate that IL-1β exerts variable effects on LTP at different kinds of synapses, indicating that IL-1β has synapse-specific effects on hippocampal synaptic plasticity.The immune system and brain constantly communicate with each other in both sickness and health.

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Section: Resultsmentioning

confidence: 99%

Synapse-specific effects of IL-1β on long-term potentiation in the mouse hippocampus

et al. 2017

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“…We would like to comment that despite this concentration could be considered quite high, the fact is it is not. Concentrations inside carrying vesicles are around 250 mM [30], warranting transients of high concentrations liberated in the synaptic clefts [56]. Figure 1 shows the calorimetric profiles of DPPC:SM and DPPC:DPPA vesicles interacting with ACh and LGlu (excitatory neurotransmitters) and GABA (an inhibitory neurotransmitter).…”

Section: Resultsmentioning

confidence: 99%

Calcium and protons affect the interaction of neurotransmitters and anesthetics with anionic lipid membranes

Pérez-Isidoro¹,

Ruiz‐Suárez²

2016

Biochimica et Biophysica Acta (BBA) - Biomembranes

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We study how zwitterionic and anionic biomembrane models interact with neurotransmitters (NTs) and anesthetics (ATs) in the presence of Ca(2+) and different pH conditions. As NTs we used acetylcholine (ACh), γ-aminobutyric acid (GABA), and l-glutamic acid (LGlu). As ATs, tetracaine (TC), and pentobarbital (PB) were employed. By using differential scanning calorimetry (DSC), we analyzed the changes such molecules produce in the thermal properties of the membranes. We found that calcium and pH play important roles in the interactions of NTs and ATs with the anionic lipid membranes. Changes in pH promote deprotonation of the phosphate groups in anionic phospholipids inducing electrostatic interactions between them and NTs; but if Ca(2+) ions are in the system, these act as bridges. Such interactions impact the physical properties of the membranes in a similar manner that anesthetics do. Beyond the usual biochemical approach, we claim that these effects should be taken into account to understand the excitatory-inhibitory orchestrated balance in the nervous system.

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“…Without significantly altering activation of receptors in the synaptic cleft, EAAC1 reduces recruitment of perisynaptic/extrasynaptic NR2B-containing NMDARs, thereby facilitating induction of long-term potentiation by short bursts of high-frequency stimulation. If the intrinsic K d for glutamate binding is 200 M (Grewer and Rauen, 2005;Grewer et al, 2008), then rapid buffering is possible at the concentration expected perisynaptically after release (Danbolt, 2001;Scimemi and Beato, 2009) even though the turnover or cycling rate of EAAC1 (Grewer et al, 2000) is not dramatically different from GLT-1 and GLAST (Wadiche et al, 1995;Wadiche and Kavanaugh, 1998). In addition, recent studies indicate that EAAC1 regulates the abundance of AMPA receptors at synapses formed between young cortical neurons in vitro by regulating the activation of perisynaptic NR2B-containing NMDA receptors (Jarzylo and Man, 2012), further supporting a role for EAAC1 in controlling the availability of glutamate released at synapses.…”

Section: Is Eaac1 Present In Nerve Terminals?mentioning

confidence: 99%

The Density of EAAC1 (EAAT3) Glutamate Transporters Expressed by Neurons in the Mammalian CNS

et al. 2012

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The extracellular levels of excitatory amino acids are kept low by the action of the glutamate transporters. Glutamate/aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1) are the most abundant subtypes and are essential for the functioning of the mammalian CNS, but the contribution of the EAAC1 subtype in the clearance of synaptic glutamate has remained controversial, because the density of this transporter in different tissues has not been determined. We used purified EAAC1 protein as a standard during immunoblotting to measure the concentration of EAAC1 in different CNS regions. The highest EAAC1 levels were found in the young adult rat hippocampus. Here, the concentration of EAAC1 was ϳ0.013 mg/g tissue (ϳ130 molecules m Ϫ3 ), 100 times lower than that of GLT-1. Unlike GLT-1 expression, which increases in parallel with circuit formation, only minor changes in the concentration of EAAC1 were observed from E18 to adulthood. In hippocampal slices, photolysis of MNI-D-aspartate (4-methoxy-7-nitroindolinyl-D-aspartate) failed to elicit EAAC1-mediated transporter currents in CA1 pyramidal neurons, and D-aspartate uptake was not detected electron microscopically in spines. Using EAAC1 knock-out mice as negative controls to establish antibody specificity, we show that these relatively small amounts of EAAC1 protein are widely distributed in somata and dendrites of all hippocampal neurons. These findings raise new questions about how so few transporters can influence the activation of NMDA receptors at excitatory synapses.

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Determining the Neurotransmitter Concentration Profile at Active Synapses

Cited by 121 publications

References 145 publications

<b>Synapse-specific effects of IL-1β on long-term potentiation in the mouse hip</b><b>pocampus </b>

<b>Synapse-specific effects of IL-1β on long-term potentiation in the mouse hip</b><b>pocampus </b>

Calcium and protons affect the interaction of neurotransmitters and anesthetics with anionic lipid membranes

The Density of EAAC1 (EAAT3) Glutamate Transporters Expressed by Neurons in the Mammalian CNS

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