Abrogation of presynaptic facilitation at hippocampal mossy fiber synapses disrupts neural ensemble activity and spatial memory
Abstract
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 synaptotagmin 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 presynaptic facilitation is suppressed at Mf-CA3 PC synapses in the absence of Syt7, without any impact on basal synaptic 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-activity 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.
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BibTeX
@article{marneffe2026abrogation,
title = {{Abrogation of presynaptic facilitation at hippocampal mossy fiber synapses disrupts neural ensemble activity and spatial memory}},
author = {Catherine Marneffe and Noelle Grosjean and Kyrian Nicolay-Kritter and Cécile Chatras and Evan R Harrell and Ashley L Kees and Christophe Mulle},
journal = {Current Biology},
year = {2026},
month = oct,
doi = {10.1016/j.cub.2026.02.027},
url = {https://hal.science/hal-05790716v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Abrogation of presynaptic facilitation at hippocampal mossy fiber synapses disrupts neural ensemble activity and spatial memory
AU - Catherine Marneffe
AU - Noelle Grosjean
AU - Kyrian Nicolay-Kritter
AU - Cécile Chatras
AU - Evan R Harrell
AU - Ashley L Kees
AU - Christophe Mulle
PY - 2026
DA - 2026/10/10
JO - Current Biology
DO - 10.1016/j.cub.2026.02.027
UR - https://hal.science/hal-05790716v1
AB - 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 synaptotagmin 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 presynaptic facilitation is suppressed at Mf-CA3 PC synapses in the absence of Syt7, without any impact on basal synaptic 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-activity 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.
SN - 0960-9822
SN - 1879-0445
ER -