Figure 4.

Glutamate release from astrocytes leads to action potential (AP) firing and TTX-insensitive neuronal synchronization. A, Paired recording from two closely spaced CA1 neurons showing spontaneous SIC activity in voltage clamp (VC, first panel on the left) and current clamp (CC, second panel) in the absence of extracellular Mg²⁺. SIC-mediated membrane depolarizations lead to action potential firing in cell 1 (for expanded traces, see inset). Subsequent application of TTX (1 μm) blocks action potential generation but not the membrane depolarizations (third panel) or SICs (last panel on the right). SICs measured in voltage clamp before and after TTX application share similar kinetics: rise time, 71.2 ± 5.7 and 75.0 ± 10.9 ms (p > 0.8); decay time, 441.1 ± 64.6 and 399.2 ± 49.4 ms (n = 21 and 31; p > 0.5), respectively. The paired recording experiment shown in this portion of this figure has an unusual high frequency of spontaneous SICs with respect to the average (Fellin et al., 2004) and is shown here because this frequency allowed a sequence of manipulations to be performed in the same experiment. Other recordings with SIC frequency similar to the average value showed similar properties. SICs and SIC-mediated depolarization frequency in each portion of the experiment shown in the figure was as follows (in SICs/min): voltage clamp, 7 ± 1; current clamp, 13 ± 5; current clamp plus TTX, 11 ± 3; voltage clamp plus TTX, 7 ± 1. B, Left, Average value of the SIC-mediated membrane depolarization in the absence (n = 36 from 5 cells) and presence (1 μm; n = 49) of TTX. Right, Average number of action potentials per SIC in the absence (n = 36 from 5 cells) and presence (n = 49) of TTX. C, Mean rise and decay time of SIC-mediated membrane depolarization under control conditions (n = 36) and in the presence of TTX (n = 49; p > 0.4). D, Paired recording from two closely spaced CA3 neurons in the presence of TTX (1 μm), showing synchronous SICs (bottom traces in voltage clamp) and membrane depolarizations (top traces in current clamp). E, The event highlighted in D is shown at an expanded timescale. F, Average membrane depolarization (left) and average amplitude (right) for SIC-mediated depolarization and for SICs in CA3 neurons (n = 8 and 16, respectively). G, Kinetics of SICs recorded from CA3 neurons in current (CC) and voltage clamp (VC) configuration (n = 8 and 16, respectively).