The Journal of Neurophysiology Vol. 87 No. 3 March 2002, pp. 1318-1328
Copyright ©2002 by the American Physiological Society

Development and Serotonergic Modulation of NMDA Bursting in Rat Trigeminal Motoneurons

 ¹Department of Physiological Science and  ²Mental Retardation Research Center, University of California at Los Angeles, Los Angeles, California 90095-1568

Hsiao, Chie-Fang, Nanping Wu, Michael S. Levine, and Scott H. Chandler. Development and Serotonergic Modulation of NMDA Bursting in Rat Trigeminal Motoneurons. J. Neurophysiol. 87: 1318-1328, 2002. The development of N-methyl-D-aspartate (NMDA)-induced burst discharge in rat trigeminal motoneurons (TMNs) between postnatal days P1 and P10 was examined using whole cell patch-clamp recording methods in brain slices. Bath application of NMDA (50 µM) induced a Mg²⁺-dependent rhythmical bursting activity starting around P8. Prior to the onset of bursting, the membrane potential depolarized and the input resistance increased. Hyperpolarization of the membrane potential with extrinsic current demonstrated a narrow window of membrane potential where maintained rhythmical burst discharge was evident. In P1-P4 neurons, NMDA application produced membrane depolarization and a minimal change in input resistance, but no burst activity at any membrane potential. Voltage-clamp analysis indicated that the bursting activity was related to the presence or absence of a voltage-dependent Mg²⁺ block and induction of a negative slope conductance (NSC) region in the I_NMDA-V relationship. Regardless of age, reduction of extracellular Mg²⁺ from 1 mM to 30 µM enhanced I_NMDA at voltages negative to 60 mV. However, in 1 mM Mg²⁺, P1-P4 neurons were devoid of a prominent NSC region compared with P8-P10 neurons, suggesting that the efficacy of depolarization in unblocking the NMDA receptors increased with age. NMDA bursting was not dependent on calcium influx through voltage-gated calcium channels (VGCC) but did require a minimal concentration of Ca²⁺ in the bath. Intracellular bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid application suppressed burst discharge completely, suggesting that intracellular Ca²⁺ directly, or via second-messenger systems, regulates NMDA receptor activity and bursting. Interestingly, NMDA bursting could be induced in P1-P4 neurons by simultaneous bath application of serotonin (5-HT, 10 µM), which by itself did not produce bursting, suggesting an "enabling" role for 5-HT. Voltage-clamp analysis demonstrated that the NMDA/5-HT bursting resulted from induction of an NSC in the I-V relationship of total membrane current. 5-HT by itself produced no such effect. The mechanisms for this effect were due to an enhancement of the NSC region of the I_NMDA-V relationship and reduction of a presumed leak current by 5-HT. These data indicate that NMDA bursting in trigeminal motoneurons is developmentally regulated and subject to neuromessenger modulation. Control of the Mg²⁺ sensitivity of the NMDA receptor and voltage-dependent block by neuromessengers could be an effective means to control the efficacy of glutamatergic synaptic drive to motoneurons during rhythmical oral-motor activity at early postnatal ages.