Control of E-S Potentiation at two different sites in the dendro-somatic axis

EPSP-Spike (E-S) Potentiation occurs alongside synaptic Long-Term Potentiation (LTP), both triggered by high-frequency synaptic stimulation (HFS). In this study, we confirm the earlier findings that E-S potentiation appears to be prevented by prior reduction of GABAA receptor-mediated inhibitory synaptic transmission. However, we demonstrate that this is a result of an occlusion of E-S potentiation, not a block. E-S potentiation and GABAA antagonism each saturate postsynaptic action potential discharge, but E-S potentiation can still be induced by high frequency activation of synapses, even in the presence of pharmacological GABAA blockade. These results suggest that GABAA blockers/antagonists and E-S potentiation share an expression mechanism, namely the reduction of GABAA-mediated synaptic inhibition. We also assayed changes in the electrical coupling between dendrite and soma, and were surprised to find that this coupling is decreased following HFS, a change that would oppose E-S potentiation. This decrease in dendritic-soma electrical coupling (D-S coupling) was induced through the action of GABAB receptors, but not maintained or expressed via the activity of these receptors. These data all together suggest that there are two distinct and opposing changes that occur as a result of HFS: 1) A decrease in passive dendro-somatic electrical coupling, and 2), an increase in coupling between the somatic EPSP and action potential generation. These two opposing influences may function as a homeostatic mechanism to balance the excitatory/inhibitory relationship between primary neurons and interneurons, and may represent a separate mechanism by which feedback and feed-forward synaptic inhibition can influence E-S coupling in opposite directions. Significance statementE-S Potentiation is an activity-dependent form of plasticity that boosts the efficiency of the coupling between synaptic input and action potential output in a neuron. Because it is induced by synaptic activity in series with the more familiar long-term potentiation (LTP), and is similarly persistent, it represents an additional mechanism by which memory traces may be stored within neural circuits. The significance of this paper is that it shows that there are at least two points of control for E-S potentiation which influence it in opposite directions, thereby providing additional basic mechanisms by which memory traces may be modulated.