ELECTROPHYSIOLOGICAL CHARACTERIZATION OF EXCITATORY AMINO-ACID RESPONSES IN RAT LATERAL PARABRACHIAL NEURONS INVITRO

The pontine parabrachial nucleus (PBN) is a major recipient of a diver se array of autonomic-related information from the caudal brainstem. R ecent data indicate the presence of glutamate-like immunoreactivity wi thin this nucleus. The effect of specific excitatory amino acid (EAA) receptor agonists and antagonists were studied in the lateral PBN (LPB N) by the use of whole-cell patch recordings in an in vitro brainstem slice preparation. Under current and voltage clamp conditions, indepen dent bath applications of N-methyl-D-aspartate (NMDA; 10 muM), quisqua lic acid (QUIS; 10 muM) and kainic acid (kainate; 10 muM) evoked membr ane depolarization and an inward current in 28 of 31 LPBN neurons. In voltage clamp mode, the NMDA current (I(NMDA)) was undetectable at pot entials negative to -70 mV and a small inward current was observed at more depolarized potentials. However, in the absence of external Mg2+, the voltage dependence of I(NMDA) was similar to that observed for QU IS and kainate. The allosteric modulation of the NMDA receptor by the strychnine-insensitive glycine binding site was examined by the applic ation of the amino acid D-serine (0.5 mM). A marked and sustained pote ntiation of the steady-state I(NMDA) (-60 mV holding potential) was ob served. The selective NMDA-antagonist DL-2-amino-5-phosphonovaleric ac id (APV; 10 muM) completely and reversibly blocked the NMDA-induced cu rrent, that was maximized in the absence of external Mg2+. Furthermore , this dose of APV was found to reversibly reduce the firing frequency of spontaneously active LPBN neurons. The lpha-amino-3-hydroxy-5-meth yl-4-isoxazolepropionic acid (AMPA)/kainate receptor selective antagon ist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10 muM) strongly atten uated QUIS-evoked responses without influencing the resting current. C NQX also reversibly reduced the firing rate of spontaneously active LP BN neurons. These results suggest that LPBN neurons, which are implica ted in cardiovascular regulatory responses, express both NMDA and non- NMDA receptors. Furthermore, EAAs may serve an important function in r egulating the basal excitability of LPBN neurons.