Abrogation of presynaptic facilitation at hippocampal mossy fiber synapses impacts neural ensemble activity and spatial memory

Presynaptic short-term plasticity is thought to play a major role in the process of spike transfer within local circuits. Mossy fiber synapses between the axons of dentate gyrus (DG) granule cells and CA3 pyramidal cells (Mf-CA3 synapses) display a remarkable extent of presynaptic plasticity which endows these synaptic connections with detonator properties. The pattern of action potential firing, in the form of high frequency bursts in the DG, strongly controls the amplitude of synaptic responses and information transfer to CA3. Here we have investigated the role of presynaptic facilitation at Mf-CA3 synapses in the operation of CA3 circuits in vivo and in memory encoding. Syt7, a calcium sensor necessary for presynaptic facilitation, was selectively abrogated, in DG granule cells using Syt7 conditional KO mice (DG Syt7 KO mice). In hippocampal slices, we extend previous analysis to show that short-term presynaptic facilitation is selectively suppressed at Mf-CA3 synapses in the absence of Syt7, without any impact on basal synaptic properties and long-term potentiation. Short-term plasticity was found to be crucial for spike transfer between the DG and CA3 in conditions of naturalistic patterns of presynaptic firing. At the network level, in awake head-fixed mice, the abrogation of short-term plasticity largely reduced the co-activity of CA3 pyramidal cells. Finally, whereas DG Syt7 KO mice are not impaired in behavioral tasks based on pattern separation, they show deficits in spatial memory tasks which rely on the process of pattern completion. These results shed new light on the role of the detonator properties of DG-CA3 synapses, and give important insights into how this key synaptic feature translate at the population and behavioral levels.