Abrogation of presynaptic facilitation at hippocampal mossy fiber synapses disrupts 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 (Mf) synapses between the axons of dentate gyrus (DG) granule cells (GCs) and cornu
ammonis area 3 pyramidal cells (CA3-PCs) (Mf-CA3 synapses) display a remarkable extent of presynaptic
plasticity. Here, we have investigated the role of short-term presynaptic facilitation at Mf synapses in the
operation of CA3 circuits in vivo and in memory encoding by analyzing mice with selective abrogation of syn-
aptotagmin 7 (Syt7) in DG granule cells (DG-Syt7 knockout [KO] mice), hence in all presynaptic Mf targets,
including mossy cells and interneurons (INs). We extend previous studies to show that short-term presynap-
tic facilitation is suppressed at Mf-CA3 PC synapses in the absence of Syt7, without any impact on basal syn-
aptic properties and on long-term potentiation (LTP). 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 facilitation was associated with reduced co-ac-
tivity of CA3-PCs. Finally, DG-Syt7 KO mice show deficits in spatial memory tasks that rely on the process of
pattern completion, but not on pattern separation, and display altered emotional processes. These results
give important insights into how short-term presynaptic facilitation of DG-CA3 synapses may contribute to
hippocampal function at the circuit and behavioral levels.

Auteurs Bordeaux Neurocampus