TETANUS-INDUCED SUSTAINED POTENTIATION OF MONOSYNAPTIC INHIBITORY TRANSMISSION IN THE RAT MEDULLA - EVIDENCE FOR A PRESYNAPTIC LOCUS

1. Whole cell voltage-clamp recordings were made from dorsomedial nucl eus tractus solitarii (dmNTS) neurons in coronal rat medullary slices. Synaptic activity was evoked by electrical stimulation in the region of the tractus solitarius (TS). Excitatory postsynaptic current/inhibi tory postsynaptic current (EPSC/IPSC) complexes were recorded with K-g luconate-containing electrodes. Monosynaptic, gamma-aminobutyric acid- A (GABA(A)) receptor-mediated evoked IPSCs (evIPSCs) were recorded in the presence of D(-)2-amino-5-phosphonopentanoic acid (AP5, 50 mu M) a nd 6,7-dinitroquinoxaline-2,3-dione (DNQX, 10 mu M) with CsCl-containi ng electrodes. Control synaptic stimulation was applied at 0.1 Hz. 2. Tetanic stimulation (50 Hz, 2 s) produced an increase in the 10-90% ri se time of the evIPSC component of mixed EPSC/IPSC complexes (assessed at V-hold = 0 mV) in three of eight recordings that remained signific antly potentiated above control for >15 min. This potentiation was fur ther characterized with the use of Cs-containing electrodes. Tetanus s imilarly potentiated the amplitude of monosynaptic evIPSCs by 168.0 +/ - 10.4% (mean +/- SE) control at 15 min posttetanus in 49 of 114 recor dings. This tetanus-induced sustained potentiation of monosynaptic evI PSCs (TIP) was reproducible after recovery to control levels.3. High M g2+/low Ca2+ solutions reversibly blocked induction of TIP. TIP was re producible in slices treated (>7 min) with the N-type voltage-dependen t Ca2+ channel (VDCC) antagonist omega-conotoxin-GVIA (1 mu M) or L-ty pe channel blocker nimodipine (10 mu M), but not in those slices treat ed with either omega-agatoxin-IVA (200 nM, 20 min) or omega-conotoxin- MVIIC (2 mu M). 4. The GABA(B) receptor antagonist CGP35348 (100 mu M) reversibly blocked induction of TIP, reduced resting, and blocked tet anus-induced increases in spontaneous IPSC frequency. Spontaneous IPSC amplitude was unaffected by CGP35348. 5. These results suggest a pres ynaptic locus for TIP in dmNTS, which depends in part on Ca2+ influx t hrough P/Q-type VDCCs.