How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus

programmed text How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network José Guzmán author 30CC5506-F248-11E8-B48F-1D18A9856A870000-0003-2209-5242 Alois Schlögl author 45BF87EE-F248-11E8-B48F-1D18A9856A870000-0002-5621-8100 Claudia Espinoza Martinez author 31FFEE2E-F248-11E8-B48F-1D18A9856A870000-0003-4710-2082 Xiaomin Zhang author 423EC9C2-F248-11E8-B48F-1D18A9856A870000-0003-0256-6529 Benjamin Suter author 4952F31E-F248-11E8-B48F-1D18A9856A870000-0002-9885-6936 Peter M Jonas author 353C1B58-F248-11E8-B48F-1D18A9856A870000-0001-5001-4804 PeJo department ScienComp department Pattern separation is a fundamental brain computation that converts small differences in input patterns into large differences in output patterns. Several synaptic mechanisms of pattern separation have been proposed, including code expansion, inhibition and plasticity; however, which of these mechanisms play a role in the entorhinal cortex (EC)–dentate gyrus (DG)–CA3 circuit, a classical pattern separation circuit, remains unclear. Here we show that a biologically realistic, full-scale EC–DG–CA3 circuit model, including granule cells (GCs) and parvalbumin-positive inhibitory interneurons (PV+-INs) in the DG, is an efficient pattern separator. Both external gamma-modulated inhibition and internal lateral inhibition mediated by PV+-INs substantially contributed to pattern separation. Both local connectivity and fast signaling at GC–PV+-IN synapses were important for maximum effectiveness. Similarly, mossy fiber synapses with conditional detonator properties contributed to pattern separation. By contrast, perforant path synapses with Hebbian synaptic plasticity and direct EC–CA3 connection shifted the network towards pattern completion. Our results demonstrate that the specific properties of cells and synapses optimize higher-order computations in biological networks and might be useful to improve the deep learning capabilities of technical networks. https://research-explorer.ista.ac.at/download/10110/10114/patternseparation-main (1).zip application/x-zip-compressedno https://opensource.org/licenses/GPL-3.0 IST Austria2021 10.15479/AT:ISTA:10110 https://research-explorer.ista.ac.at/record/10816 https://ist.ac.at/en/news/spot-the-difference/ J. Guzmán, A. Schlögl, C. Espinoza Martinez, X. Zhang, B. Suter, P.M. Jonas, (2021). Guzmán, J., Schlögl, A., Espinoza Martinez, C., Zhang, X., Suter, B., & Jonas, P. M. (2021). How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network. IST Austria. <a href="https://doi.org/10.15479/AT:ISTA:10110">https://doi.org/10.15479/AT:ISTA:10110</a> Guzmán, José, Alois Schlögl, Claudia Espinoza Martinez, Xiaomin Zhang, Benjamin Suter, and Peter M Jonas. “How Connectivity Rules and Synaptic Properties Shape the Efficacy of Pattern Separation in the Entorhinal Cortex–Dentate Gyrus–CA3 Network.” IST Austria, 2021. <a href="https://doi.org/10.15479/AT:ISTA:10110">https://doi.org/10.15479/AT:ISTA:10110</a>. J. Guzmán, A. Schlögl, C. Espinoza Martinez, X. Zhang, B. Suter, and P. M. Jonas, “How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network.” IST Austria, 2021. Guzmán, José, et al. <i>How Connectivity Rules and Synaptic Properties Shape the Efficacy of Pattern Separation in the Entorhinal Cortex–Dentate Gyrus–CA3 Network</i>. IST Austria, 2021, doi:<a href="https://doi.org/10.15479/AT:ISTA:10110">10.15479/AT:ISTA:10110</a>. Guzmán J, Schlögl A, Espinoza Martinez C, Zhang X, Suter B, Jonas PM. How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network. 2021. doi:<a href="https://doi.org/10.15479/AT:ISTA:10110">10.15479/AT:ISTA:10110</a> Guzmán J, Schlögl A, Espinoza Martinez C, Zhang X, Suter B, Jonas PM. 2021. How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network, IST Austria, <a href="https://doi.org/10.15479/AT:ISTA:10110">10.15479/AT:ISTA:10110</a>. 101102021-10-08T06:44:22Z2026-07-15T22:30:45Z