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Ambient glutamate levels under astrocytic control enhance excitability of supraoptic nucleus (SON) neurons. An in vitro and in vivo study
Author(s) -
Fleming Tiffany Marie,
Scott Victoria,
Brown Colin H.,
Stern Javier E
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.792.16
Subject(s) - tonic (physiology) , glutamate receptor , nmda receptor , ifenprodil , chemistry , microdialysis , neurotransmission , neuroscience , electrophysiology , medicine , endocrinology , extracellular , receptor , biology , biochemistry
In addition to mediating conventional quantal synaptic transmission, glutamate (GLU) mediates a persistent, tonic form of excitation (GLU tonic ) mediated by NMDA receptors. Here, we aimed to determine 1) if ambient GLU tonically activates NMDARs in SON neurons 2) the role of astrocytes in regulating GLU tonic 3) the functional relevance of GLU tonic and 4) if GLU tonic is altered in dehydration (48DH). In electrophysiological recordings obtained from hypothalamic slices, the NMDA receptor antagonist D‐AP5 blocked a tonic inward current of 54.0. ±2.4 pA, a proportion of which (35.3%) was sensitive to the NR2B subunit selective blocker ifenprodil. Blockade of the glial glutamate transporter GLT‐1 by dihydrokainate (DHK) increased GLU tonic (23.3 pA ± 2.0 pA, n = 7, P < 0.01) but effects were blunted in 48DH rats (13.5 pA ± 1.0 pA, n = 5). In single‐unit extracellular recordings obtained from SON neurons in vivo , firing rate was higher in 48DH rats (10.5 ± 2.1 Hz, n = 12, P<0.01) than in controls (4.2 ± 0.6 Hz, n = 11). Microdialysis administration of DHK increased SON neuron firing rate (by 121.7 ± 31.3%, n = 7, P < 0.02) in controls, but not in 48DH rats (4.3 ± 7.3%, n = 4). Our results support that by controlling ambient GLU levels, SON astrocytes regulate GLU tonic and SON neuronal activity, a function that is diminished during dehydration. Ongoing experiments assess the effects of GLU tonic on SON somatodendritic VP and OT release. Supported by NIH RO1HL68725 , NIH R01HL090948‐01, the Otago School of Medical Sciences Bequest Fund, NSF EAPSI.