Fig. 5.
Gliotransmission drives increased action potential generation in MSNs at up-state membrane potentials. (A) Average traces of SICs (n = 19) at holding potentials of −85 and −65 mV showing the enhancement of SIC amplitude at up-state (−65 mV) compared with down-state (−85 mV) membrane potentials (error bars are SEM). All experiments reported in this figure were made in 1 mM Mg2+-containing ACSF. (B) Average amplitude of the SICs at the two different holding potentials. (C) Average SIC frequency after stimulation of class I mGluRs with DHPG (20 μM) at Vh of −85 and −65 mV (n = 10). (D) The EPSC (Left) and pure NMDA-mediated EPSC (Right) at holding potentials of −85 and −65 mV. NMDA currents were recorded in NBQX (30 μM). Note the reduction of EPSC amplitude at up-state (−65 mV) compared with down-state (−85 mV) membrane potentials in contrast to the augmentation of the SIC (A). Traces in D are averages of 10 evoked EPSCs. (E) −65/−85 mV ratio of amplitude the EPSC and pure NMDA-mediated EPSC currents at the two different voltages (n = 5). (F) Paired whole-cell recordings from two closely spaced MSNs in Mg2+-containing ACSF. Glutamatergic afferents were stimulated with 10 trains of seven 30-Hz stimuli (one train shown) that evoked EPSPs in the neuron recorded in current-clamp (Upper) and EPSCs in the voltage-clamped neuron (Lower). With a delay after afferent stimulation, synchronous excitation of paired MSNs show that gliotransmission powerfully excites MSNs to generate a burst of action potentials. (G) In contrast, gliotransmission evokes few action potentials when MSNs are at down-state membrane potentials. (H) Comparison on the kinetics of SICs at up- and down-state membrane potentials (n = 13 events). (I) Average number of action potentials during gliotransmission-mediated depolarization (black bars, n = 6; gray bars, n = 5).