Herman MA, Jahr CE. Extracellular glutamate concentration in hippocampal slice. J Neurosci 27: 9736-9741

Oregon Health and Science University, Portland, Oregon, United States
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 10/2007; 27(36):9736-41. DOI: 10.1523/JNEUROSCI.3009-07.2007
Source: PubMed


Synaptic glutamate transients resulting from vesicular exocytosis are superimposed on a low baseline concentration of glutamate in the extracellular space. Reported values of baseline glutamate concentrations range up to 4 microM. If glutamate were present tonically at low micromolar concentrations, many receptors, especially the high-affinity NMDA receptors (NMDARs), would be activated or desensitized, altering neuronal excitability. Using NMDARs expressed by CA1 pyramidal cells in acute hippocampal slices to monitor extracellular glutamate, we find that its baseline concentration is much lower, near 25 nM. In addition, superfusion of low micromolar concentrations of glutamate had no effect on neurons, indicating that glutamate transport prevents access to receptors within the slice. However, equipotent concentrations of NMDA, a nontransported agonist, depolarized neurons dramatically. We suggest that ambient concentrations of glutamate in vivo are also in the nanomolar range and are too low to cause significant receptor activation.

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    • "In vitro experiments showed a 10-fold reduction in glutamate uptake by primary glioblastoma cells compared to normal astrocytes. In addition, these glioblastoma cells are able to release significant quantities of glutamate, resulting in an increase in glutamate concentration in the range of 100 to 700 µM[84], well above the extracellular glutamate concentrations measured in normal brain tissues (25 nM -0.6 µM)[128,129]. This capacity of glioblastoma cells to release glutamate has been observed also in ambulatory patients using microdialysis probes[130]. "

    Full-text · Article · Jan 2016 · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
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    • "Thus, estimates of the basal concentration of glutamate within the extracellular space vary over three orders of magnitude, ranging from 0.02 to 30 μm, and depend on the methods of measurement (Herman and Jahr, 2007; Chefer et al., 2009; Moussawi et al., 2011). Estimates of ambient glutamate based on microdialysis measurements are approximately 100-fold higher than those based on electrophysiological measurements of tonic NMDA receptor activity (Suna et al., 2014). "
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    ABSTRACT: Mechanisms for maintenance of the extracellular level of glutamate in brain tissue and its regulation still remain almost unclear, and criticism of the current paradigm of glutamate transport and homeostasis has recently appeared. The main premise for this study is the existence of a definite and non-negligible concentration of ambient glutamate between the episodes of exocytotic release in our experiments with rat brain nerve terminals (synaptosomes), despite the existence of a very potent Na+-dependent glutamate uptake. Glutamate transporter reversal is considered as the main mechanisms of glutamate release under special conditions of energy deprivation, hypoxia, hypoglycemia, brain trauma, and stroke, underlying an increase in the ambient glutamate concentration and development of excitotoxicity. In the present study, a new vision on transporter-mediated release of glutamate as one of the main mechanisms involved in the maintenance of definite concentration of ambient glutamate under normal energetical status of nerve terminals is forwarded. It has been suggested that glutamate transporters act effectively in outward direction in a non-pathological manner, and this process is thermodynamically synchronized with uptake and provides effective outward glutamate current, thereby establishing and maintaining permanent and dynamic glutamatein/glutamateout gradient and turnover across the plasma membrane. In this context, non-transporter tonic glutamate release by diffusion, spontaneous exocytosis, cystine-glutamate exchanger, and leakage through anion channels can be considered as a permanently added 'new' exogenous substrate using two-substrate kinetic model calculations. Permanent glutamate turnover is of value for tonic activation of post/presynaptic glutamate receptors, long-term potentiation, memory formation, etc. Counterarguments against this mechanism are also considered.
    Full-text · Article · Jan 2016 · Reviews in the neurosciences
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    • "The presence of AMPARs may be important for responding to local activity-driven glutamate release and it has been proposed that glutamate transporters in Type 1 cells contribute to transmitter clearance (Regan and Smalley, 2007; Regan et al., 2007). However the functional impact of AMPARs and glutamate transporters in the absence of synaptic innervation needs further clarification since the ambient extracellular concentration of glutamate is extremely low (Herman and Jahr, 2007). "
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    ABSTRACT: The dentate gyrus is the entrance of the hippocampal formation and a primary target of excitatory afferents from the entorhinal cortex that carry spatial and sensory information. Mounting evidence suggests that continual adult neurogenesis contributes to appropriate processing of cortical information. The ongoing integration of adult born neurons dynamically modulates connectivity of the network, potentially contributing to dentate cognitive function. Here we review the current understanding of how glutamatergic innervation develops during the progression of adult-born neuron maturation. Summarizing the developmental stages of dentate neurogenesis, we also demonstrate that new neurons at an immature stage of maturation begin to process afferent activity from both medial and lateral entorhinal cortices. © 2015, Higher Education Press and Springer-Verlag Berlin Heidelberg.
    Full-text · Article · Jul 2015
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