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 nucleus 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/inhibitory postsynaptic current (EPSC/IPSC) complexes were recorded with K-gluconate-containing electrodes. Monosynaptic, gamma-aminobutyric acid-A (GABAA) receptor-mediated evoked IPSCs (evIPSCs) were recorded in the presence of D(-)2-amino-5-phosphonopentanoic acid (AP5, 50 microM) and 6,7-dinitroquinoxaline-2,3-dione (DNQX, 10 microM) with CsCl-containing electrodes. Control synaptic stimulation was applied at 0.1 Hz. 2. Tetanic stimulation (50 Hz, 2 s) produced an increase in the 10-90% rise time of the evIPSC component of mixed EPSC/IPSC complexes (assessed at Vhold = 0 mV) in three of eight recordings that remained significantly potentiated above control for > 15 min. This potentiation was further characterized with the use of Cs-containing electrodes. Tetanus similarly potentiated the amplitude of monosynaptic evIPSCs by 168.0 +/- 10.4% (mean +/- SE) control at 15 min posttetanus in 49 of 114 recordings. This tetanus-induced sustained potentiation of monosynaptic evIPSCs (TIP) was reproducible after recovery to control levels. 3. High Mg2+/low Ca2+ solutions reversibly blocked induction of TIP. TIP was reproducible in slices treated (> 7 min) with the N-type voltage-dependent Ca2+ channel (VDCC) antagonist omega-conotoxin-GVIA (1 microM) or L-type channel blocker nimodipine (10 microM), but not in those slices treated with either omega-agatoxin-IVA (200 nM, 20 min) or omega-conotoxin-MVIIC (2 microM). 4. The GABAB receptor antagonist CGP35348 (100 microM) reversibly blocked induction of TIP, reduced resting, and blocked tetanus-induced increases in spontaneous IPSC frequency. Spontaneous IPSC amplitude was unaffected by CGP35348. 5. These results suggest a presynaptic locus for TIP in dmNTS, which depends in part on Ca2+ influx through P/Q-type VDCCs.