DUAL COMPONENT EXCITATORY AMINO ACID MEDIATED RESPONSES IN TRIGEMINAL MOTONEURONS AND THEIR MODULATION BY SEROTONIN IN VITRO. Trueblood, P.R., M.S. Levine, and S.H. Chandler. Department of Physiological Science and the Mental Retardation Research Center, University of California at Los Angeles, California 90095.
APStracts 3:0112N, 1996.
1. Intracellular recordings were made from guinea pig trigeminal motoneurons (TMNs) in brainstem slices. Monosynaptic excitatory synaptic potentials (EPSP) were evoked in TMNs by focal stimulation of the Mesencephalic Nucleus of V (Mes V), a region containing cell bodies of primary afferent fibers of jaw muscle spindle and periodontal receptor origin. 2. The presence of N-methyl- D,L-aspartate (NMDA) and non-NMDA excitatory amino acid receptors (EAA) was determined by iontophoretic application of NMDA and ( + )- [alpha] -amino-3- hydroxy-5-methylisoxazole-4-propionic acid (AMPA) from multibarrelled micropipettes. Application of either agonist in normal Mg 2+ -containing extracellular solutions produced a membrane depolarization or inward current from resting potential in current or voltage clamp modes, respectively. However, the voltage and current responses to NMDA and AMPA differed in their dependence on initial membrane potential. In voltage clamp between -70 and -50 mV the peak current response to NMDA application increased while the response to AMPA application decreased as a function of holding potential. 3. Mes V induced synaptic potentials were examined for the presence of NMDA and non- NMDA components in extracellular solutions devoid of Mg 2+ . In the presence of DL-2-amino-5-phosphonopentanoic acid (AP5, 30[mu]M) the peak amplitude and half-amplitude duration were decreased 52% and 36% (n=2), respectively, compared to control. In the presence of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX,10-15 [mu]M), a specific non-NMDA antagonist, the mean decrease in evoked synaptic potential amplitude was 55% (n=5) but the half-amplitude duration increased by a mean of 63% (n=5). 4. The non-NMDA component of the evoked EPSP obtained in the presence of APV showed a linear decrease in peak amplitude as a function of holding potential. In contrast, the NMDA EPSP component obtained in the presence of CNQX increased in peak amplitude as a function of holding potential between -70 and -40 mV. The increase in EPSP peak amplitude was abolished by removal of Mg 2+ from the extracellular media. 5. Bath application of 5-HT (50-100 [mu]M) increased the peak NMDA and non- NMDA EPSP components by 31% (n=10) and 23% (n=8), respectively, while producing a mean increase in half-amplitude duration of 67% and 88%, respectively. Concomitantly, 5-HT increased input resistance by approximately 40% and produced a membrane depolarization. 6. In the presence of tetrodotoxin (TTX), serotonin (5-HT) enhanced both iontophoretic NMDA and AMPA voltage responses. In cells voltage clamped between -60 and -70 mV in Mg 2+ -free solutions, iontophoretic NMDA and AMPA peak currents were enhanced 27% and 32% by 5-HT, respectively. 7. The enhancement of the iontophoretic NMDA and non- NMDA responses was mimicked by (+/-)-1-(2,5-Dimethyoxy-4-iodophenyl)-2- aminopropane HCL (DOI), and blocked by ketanserin and mesulergine suggesting 5-HT 2 receptor involvement. 8. The results demonstrate that trigeminal motoneurons posses both NMDA and non-NMDA receptors which are activated during Mes V-induced synaptic transmission. The data suggest that EAA mediated responses in trigeminal motoneurons are substrates for modulation by 5-HT via changes in membrane resistance and modulation of the EAA- induced synaptic current.

Received 13 December 1995; accepted in final form 21 May 1996.
APS Manuscript Number J846-5.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 17 June 96