[Abstract Title]. - Society for Neuroscience

Poster
242. Glial Neuronal Interactions: Glutamate and Calcium
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 242.8/I3
Topic: B.11.a. Synapses
Title: Impaired glutamate uptake increases activation of synaptic and extrasynaptic NMDA
receptors in the spinal substantia gelatinosa (SG) neurons
Authors: *H. NIE, H.-R. WENG;
MD Anderson Cancer Ctr., Houston, TX
Abstract: Activation of N-methyl-D-aspartate (NMDA) receptors in spinal dorsal horn neurons
is a key process related to sensory transmission, neural plasticity, and pathogenesis of pain. In
this study, we investigated how activation of NMDA receptors in spinal SG neurons is regulated
by glutamate re-uptake through glutamate transporters located in the astrocytic and neuronal
plasma membrane. Using visualized whole cell patch recording techniques, we analyzed NMDA
excitatory postsynaptic currents (EPSCs) evoked by graded inputs from primary afferents
recorded in spinal slices of young adult rats before and after pharmacological blockade of both
glial and neuronal glutamate transporters by DL-threo-β-benzyloxyaspartate (DL-TBOA).
Blockade of glutamate transporters led to increases in the number and duration of NMDA
receptors activated by monosynaptic or polysynaptic inputs and exogenous glutamate. Blockade
of glutamate transporters also resulted in increased activation of NR2B subunits by primary
afferent inputs. The degree of enhancement in activation of NMDA receptors induced by DL-
TBOA was greater in neurons having weaker synaptic input at baseline than in those having
stronger synaptic input. We observed that impaired glutamate uptake caused glutamate spillover
outside the active synaptic cleft and activation of NMDA receptors outside the active synapses,
including extrasynaptic NMDA receptors and NMDA receptors in neighboring synapses.
Blockade of glutamate transporters also caused glutamate accumulation and dwelling, leading to
increased activation of unsaturated NMDA receptors and prolonged the duration of NMDA
receptors activated. Taken together, our results indicate that the number, duration, and type of
NMDA receptors activated in spinal SG neurons are regulated by glutamate transporters.
Reversing impaired glutamate uptake may be a new avenue to relieve the pathological pain
related to abnormal activation of NMDA receptors.
Supported by funds from The University of Texas M. D. Anderson Cancer Center to H.R.W.
Disclosures: H. Nie , None; H. Weng, None.
Poster