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Astrocyte glutamate transporters regulate metabotropic glutamate receptor-mediated excitation of hippocampal interneurons.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Huang, Yanhua H. Tanaka, Kohichi Rothstein, Jeffrey D. Bergles, Dwight E. |
| Copyright Year | 2004 |
| Abstract | Clearance of extracellular glutamate is essential for limiting the activity of metabotropic glutamate receptors (mGluRs) at excitatory synapses; however, the relative contribution of transporters found in neuronal and glial membranes to this uptake is poorly understood. Hippocampal interneurons located at the oriens-alveus border express mGluR1alpha, a metabotropic glutamate receptor that regulates excitability and synaptic plasticity. To determine which glutamate transporters are essential for removing glutamate at these excitatory synapses, we recorded mGluR1-mediated EPSCs from oriens-lacunosum moleculare (O-LM) interneurons in acute hippocampal slices. Stimulation in stratum oriens reliably elicited a slow mGluR1-mediated current in O-LM interneurons if they were briefly depolarized to allow Ca2+ entry before stimulation. Selective inhibition of GLT-1 [for glutamate transporter; EAAT2 (for excitatory amino acid transporter)] with dihydrokainate increased the amplitude of these responses approximately threefold, indicating that these transporters compete with mGluRs for synaptically released glutamate. However, inhibition of all glutamate transporters with TBOA (DL-threo-b-benzyloxyaspartic acid) increased mGluR1 EPSCs >15-fold, indicating that additional transporters also shape activation of these receptors. To identify these transporters, we examined mGluR1 EPSCs in mice lacking GLAST (for glutamate-aspartate transporter; EAAT1) or EAAC1 (for excitatory amino acid carrier; EAAT3). A comparison of responses recorded from wild-type and transporter knock-out mice revealed that the astroglial glutamate transporters GLT-1 and GLAST, but not the neuronal transporter EAAC1, restrict activation of mGluRs in O-LM interneurons. Transporter-dependent potentiation of mGluR1 EPSCs led to a dramatic increase in interneuron firing and enhanced inhibition of CA1 pyramidal neurons, suggesting that acute or prolonged disruption of transporter activity could lead to changes in network activity as a result of enhanced interneuron excitability. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.jneurosci.org/content/jneuro/24/19/4551.full.pdf |
| Alternate Webpage(s) | http://bergleslab.com/pdf/Huang_et_al_2004b.pdf |
| Alternate Webpage(s) | http://www.jneurosci.org/content/24/19/4551.full.pdf |
| PubMed reference number | 15140926v1 |
| Volume Number | 24 |
| Issue Number | 19 |
| Journal | The Journal of neuroscience : the official journal of the Society for Neuroscience |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Amino Acid Transporter Aspartic Acid Astrocytes CA1 field CA3 Stratum Lucidum DL-threo-beta-benzyloxyaspartate Excitation Excitatory Amino Acids Glutamic Acid Interneurons Knock-out Membrane Transport Proteins Neuroglia Neuronal Plasticity Pyramidal Cells Receptors, Metabotropic Glutamate SLC1A1 gene SLC1A2 gene SLC1A2 wt Allele SLC1A3 gene Structure of alveus of hippocampus Synapses Thioctic Acid Tissue membrane chemosensitization/potentiation dihydrokainate metabotropic glutamate receptor type 1 |
| Content Type | Text |
| Resource Type | Article |
