Activity-induced depression of synaptic inhibition during LTP-inducing patterned stimulation

In the hippocampus, patterns of electrical stimulation that approximate bursting neuronal activity during theta rhythm have been shown to induce a long-term potentiation (LTP) of excitatory synapses. In this study, a single subthreshold stimulus applied to one set of Schaffer/commissural fibers affected the response to a second stimulation delivered 200 ms later to a separate set of Schaffer/commissural fibers in the CA1 field of rat hippocampal slices. The first (priming) stimulus caused a prolongation of the synaptic response elicited by the second (primed) stimulus. In addition, the priming stimulation facilitated the induction of LTP by bursts of stimulation (4 pulses at 100 Hz) of the second afferent pathway. Analysis of the shape of the synaptic responses indicates that the prolongation is due to the removal of an inhibitory component rather than the addition of a novel excitatory component. Blockade of GABAA-ergic transmission with picrotoxin mimicked the priming effect in that it also widened synaptic responses and facilitated burst-induced LTP. We suggest that these patterns of stimulation result in a transient loss of inhibition during the primed stimulation. This, in turn, brings about a prolongation of the synaptic response that allows short bursts of excitatory synaptic activity to depolarize postsynaptic cells sufficiently to trigger LTP.