title: Development and serotonergic modulation of NMDA bursting in rat trigeminal motoneurons.
abstract: 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 microM) induced a Mg(2+)-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 Mg(2+) block and induction of a negative slope conductance (NSC) region in the I(NMDA)-V relationship. Regardless of age, reduction of extracellular Mg(2+) from 1 mM to 30 microM enhanced I(NMDA) at voltages negative to -60 mV. However, in 1 mM Mg(2+), 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 Ca(2+) in the bath. Intracellular bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid application suppressed burst discharge completely, suggesting that intracellular Ca(2+) 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 microM), 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 Mg(2+) 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.
authors.affiliation: Department of Physiological Science, University of California at Los Angeles, 2859 Slichter Hall, Los Angeles, CA 90095-1568, USA.
authors.forename: Chie-Fang
authors.initials: CF
authors.lastname: Hsiao
authors.forename: Nanping
authors.initials: N
authors.lastname: Wu
authors.forename: Michael S
authors.initials: MS
authors.lastname: Levine
authors.forename: Scott H
authors.initials: SH
authors.lastname: Chandler
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000502:physiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D008409:Mastication / Q000502:physiology; D009046:Motor Neurons / Q000502:physiology*; D016202:N-Methylaspartate / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010507:Periodicity; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D012701:Serotonin / Q000502:physiology*; D013391:Sucking Behavior / Q000502:physiology; D014276:Trigeminal Nerve / Q000166:cytology* / Q000502:physiology
chemical_list: D020746:Calcium Channels, L-Type; D018690:Excitatory Amino Acid Agonists; D016194:Receptors, N-Methyl-D-Aspartate; D012701:Serotonin; D016202:N-Methylaspartate; D008274:Magnesium; D002118:Calcium