Activity-dependent shifts in the glycine response. A, An example of negative glycine response shift occurring with prolonged complex spiking. An all-simple-spiking cell with an excitatory glycine response was injected 100 pA at t = 0. Complex spikes began appearing at t = 27 s. The weakly inhibitory effect of glycine at t = 23 s became more inhibitory (t = 105 s) as complex spiking continued. After termination of depolarization, the glycine responses were hyperpolarizing until the fourth response (t = 182), and the return of the excitatory response took ∼100 s (t = 242 s). Arrowheads indicate time of a 500 μm glycine puff, and the horizontal line is drawn at −70 mV for reference. B, Comparison of the change in glycine responses following simple and complex spiking. An all-simple-spiking cell with an inhibitory glycine (2 mm) response was silenced with −110 pA bias current and induced to fire late complex spikes (top) or trains of simple spikes (bottom), with an 8 s step of 250 pA and 170 pA, respectively. The horizontal line is aligned to the peaks of glycine responses before the evoked activity. Insets show magnified responses at time points marked “1” and “2.” A positive shift in the glycine response occurred (o) immediately after simple spiking.