Nicotinic EPSCs in intact rat ganglia feature depression except if evoked during intermittent postsynaptic depolarization.

The involvement of the postsynaptic membrane potential level in controlling synaptic strength at the ganglionic synapse was studied by recording nicotinic fast synaptic currents (EPSCs) from neurons in the intact, mature rat superior cervical ganglion, using the two-electrode voltage-clamp technique. EPSCs were evoked by 0.05-Hz supramaximal stimulation of the preganglionic sympathetic trunk over long periods; their peak amplitude (or synaptic charge transfer) over time appeared to depend on the potential level of the neuronal membrane where the nicotinic receptors are embedded. EPSC amplitude remained constant (n = 6) only if ACh was released within repeated depolarizing steps of the postganglionic neuron, which constantly varied between -50 and -20 mV in consecutive 10-mV steps, whereas it decreased progressively by 45% (n = 9) within 14 min when the sympathetic neuron was held at constant membrane potential. Synaptic channel activation, channel ionic permeation and depolarization of the membrane in which the nicotinic receptor is localized must occur simultaneously to maintain constant synaptic strength at the ganglionic synapse during low-rate stimulation (0.03-1 Hz). Different posttetanic (20 Hz for 10 s) behaviors were observed depending on the mode of previous stimulation. In the neuron maintained at constant holding potential during low-rate stimulation, the depressed EPSC showed posttetanic potentiation, recovering approximately 23% of the mean pretetanic values (n = 10). The maximum effect was immediate in 40% of the neurons tested and developed over a 3- to 6-min period in the others; thereafter potentiation vanished within 40 min of 0.05-Hz stimulation. In contrast, no statistically significant synaptic potentiation was observed when EPSC amplitudes were kept constant by repeated -50/-20-mV command cycles (n = 12). It is suggested that, under these conditions, posttetanic potentiation could represent an attempt at recovering the synaptic strength lost during inappropriate functioning of the ganglionic synapse.