{"id":1756,"date":"2004-05-12T00:00:33","date_gmt":"2004-05-12T00:00:33","guid":{"rendered":"http:\/\/bergleslab.com\/wordpress\/?p=1756"},"modified":"2017-10-18T19:57:18","modified_gmt":"2017-10-18T19:57:18","slug":"huang-2004-3","status":"publish","type":"post","link":"http:\/\/bergleslab.com\/index.php\/2004\/05\/12\/huang-2004-3\/","title":{"rendered":"Astrocyte glutamate transporters regulate metabotropic glutamate receptor-mediated excitation of hippocampal interneurons."},"content":{"rendered":"
J Neurosci.<\/a> 2004 May 12;24(19):4551-9.<\/div>\n

Astrocyte glutamate transporters regulate metabotropic glutamate receptor-mediated excitation of hippocampal interneurons.<\/h4>\n
Huang YH<\/a>1<\/sup>, Sinha SR<\/a>, Tanaka K<\/a>, Rothstein JD<\/a>, Bergles DE<\/a>.<\/div>\n

 <\/p>\n

Abstract<\/h4>\n
\n

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. Hippocampalinterneurons 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.<\/p>\n

PDF<\/a><\/p>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

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. Hippocampalinterneurons 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.<\/p>\n","protected":false},"author":1,"featured_media":1938,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[78,33],"tags":[88,89,34,36],"class_list":["post-1756","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-original-research","category-publications","tag-glutamate-transporter","tag-hippocampus","tag-interneuron","tag-neuron-glia-interactions"],"_links":{"self":[{"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/posts\/1756","targetHints":{"allow":["GET"]}}],"collection":[{"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/comments?post=1756"}],"version-history":[{"count":4,"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/posts\/1756\/revisions"}],"predecessor-version":[{"id":2144,"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/posts\/1756\/revisions\/2144"}],"wp:featuredmedia":[{"embeddable":true,"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/media\/1938"}],"wp:attachment":[{"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/media?parent=1756"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/categories?post=1756"},{"taxonomy":"post_tag","embeddable":true,"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/tags?post=1756"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}