Abteilung Funktionelle Architektur des Gedächtnisses

Vor Kurzem haben wir das erste kognitive Paradigma für wache Nagetiere entwickelt, welches während funktioneller Magnetresonanztomografie (fMRI) durchgeführt werden kann. Im September 2018 haben wir in Zusammenarbeit mit Eike Budinger einen 9,4-Tesla-Kleintierscanner samt Labor am LIN eingeweiht.

Auch eine Verhaltensstudie mit Menschen haben wir durchgeführt, um Gedächtnisdefizite zum Beispiel bei Patienten mit posttraumatischen Störungen besser charakterisieren zu können. In Zusammenarbeit mit Emrah Düzel vom DZNE Magdeburg sind wir an Experimenten im 7-Tesla-Kernspintomografen beteiligt.

Innerhalb des Sonderforschungsbereiches 874 beschäftigten wir uns mit den neuronalen Grundlagen von Vertrautheit und wir charakterisieren im Rahmen des Sonderforschungsbereichs 779 neu identifizierte Netzwerke im Hippocampus, die dem räumlichen und nicht-räumlichen Erinnern zugeschrieben werden.
 

Unsere Forschungsschwerpunkte im Überblick:

• Charakterisierung der spezifischen Rolle der MTL-Areale im räumlichen und nicht-räumlichen Gedächtnis in Abhängigkeit von visuellen oder olfaktorischen Sinnesmodalitäten (Verhaltenstest, Gehirnläsionen und neuroanatomische Bildgebung des Gehirns)
• Bewertung von Gedächtnisleistung und Untersuchung der Reorganisation der MTL- Bereiche nach Hirnverletzungen an Amnesiemodellen (Verhaltenstests, Gehirnläsionen und neuroanatomische Bildgebung des Gehirns)
• Charakterisierung von Gedächtnisleistung und Gehirnveränderungen in alternden Modellen (Verhaltenstests und neuroanatomische Bildgebung des Gehirns)
• Entwicklung von übertragbaren Verhaltenstests und übertragbaren kognitiven Verhaltenstest im fMRT an wachen Nagetieren (Verhaltenstest, stereotaktische Chirurgie, fMRT an Tieren)

Ausgewählte Publikationen

Ku S-P, Atucha E, Alavi N, Mulla-Osman H, Kayumova R, Yoshida M, Csicsvari J, Sauvage MM. 2024. Phase locking of hippocampal CA3 neurons to distal CA1 theta oscillations selectively predicts memory performance. Cell Reports. 43(6):Article 114276. https://doi.org/10.1016/j.celrep.2024.114276

Saber Marouf B, Reboreda A, Theissen F, Kaushik R, Sauvage M, Dityatev A, Yoshida M. 2023. TRPC4 Channel Knockdown in the Hippocampal CA1 Region Impairs Modulation of Beta Oscillations in Novel Context. Biology. 12(4):Article 629.https://doi.org/10.3390/biology12040629

Schott BH, Soch J, Kizilirmak JM, Schütze H, Assmann A, Maass A, Ziegler G, Sauvage M, Richter A. 2023. Inhibitory temporo-parietal effective connectivity is associated with explicit memory performance in older adults. iScience. 26(10):Article 107765.https://doi.org/10.1016/j.isci.2023.107765

Beer Z, Vavra P, Atucha E, Rentzing K, Heinze HJ,  Sauvage MM. 2018. The memory for time and space differentially engages the proximal and distal parts of the hippocampal subfields CA1 and CA3. PLoS Biology. 16(8):e2006100. https://doi.org/10.1371/journal.pbio.2006100

Behroozi M, Chwiesko C, Ströckens F, Sauvage M, Helluy X, Peterburs J, Güntürkün O. 2018. In vivo measurement of T₁ and T₂ relaxation times in awake pigeon and rat brains at 7T. Magnetic Resonance in Medicine. 79(2):1090-1100. https://doi.org/10.1002/mrm.26722

Lux V, Masseck OA, Herlitze S, Sauvage MM. 2017. Optogenetic Destabilization of the Memory Trace in CA1: Insights into Reconsolidation and Retrieval Processes. Cerebral Cortex. 27(1):841-851. https://doi.org/10.1093/cercor/bhv282

Lux V, Atucha E, Kitsukawa T, Sauvage MM. 2016. Imaging a memory trace over half a life-time in the medial temporal lobe reveals a time-limited role of CA3 neurons in retrieval. eLife. 5(FEBRUARY2016):Article e11862. https://doi.org/10.7554/eLife.11862

Nakamura NH, Sauvage MM. 2016. Encoding and reactivation patterns predictive of successful memory performance are topographically organized along the longitudinal axis of the hippocampus. Hippocampus. 26(1):67-75. https://doi.org/10.1002/hipo.22491

Sauvage MM, Beer Z, Ekovich M, Ho L, Eichenbaum H. 2010. The caudal medial entorhinal cortex: A selective role in recollection-based recognition memory. Journal of Neuroscience. 30(46):15695-15699. https://doi.org/10.1523/JNEUROSCI.4301-10.2010

Sauvage M, Fortin N, Owens C, Yonelinas AP, Eichenbaum H. 2008. Recognition memory: opposite effects of hippocampal damage on recollection and familiarity. Nature Neuroscience. 11(1): 16-8.

Alle Publikationen der Abteilung

2024

Ku S-P, Atucha E, Alavi N, Mulla-Osman H, Kayumova R, Yoshida M, Csicsvari J, Sauvage MM. 2024. Phase locking of hippocampal CA3 neurons to distal CA1 theta oscillations selectively predicts memory performance. Cell Reports. 43(6):Article 114276. https://doi.org/10.1016/j.celrep.2024.114276

2023

Atucha E, Ku S-P, Lippert MT, Sauvage MM. 2023, Recalling gist memory depends on CA1 hippocampal neurons for lifetime retention and CA3 neurons for memory precision. Cell Reports. 42(11): 113317. https://doi.org/10.1016/j.celrep.2023.113317

Ying J, Reboreda A, YoshidaM, Brandon MP. 2023, Grid cell disruption in a mouse model of early Alzheimer's disease reflects reduced integration of self-motion cues. Current Biology. 33(12): 2425-2437.e5. https://doi.org/10.1016/j.cub.2023.04.065

Brahimi Y, Knauer B, Price AT, Valero Aracama MJ, Reboreda A, Sauvage M, Yoshida M. 2023. Persistent Firing in Hippocampal CA1 Pyramidal Cells in Young and Aged Rats. eNeuro. https://doi.org/10.1523/ENEURO.0479-22.2023

2022

Grande X, Sauvage MM, Becke A, Düzel E, Berron D. 2022. Transversal functional connectivity and scene-specific processing in the human entorhinal-hippocampal circuitry. eLife. 11:Article e76479. https://doi.org/10.7554/eLife.76479

2021

Arboit A, Ku S-P, Krautwald K, Angenstein F. 2021. Brief neuronal afterdischarges in the rat hippocampus lead to transient changes in oscillatory activity and to a very long-lasting decline in BOLD signals without inducing a hypoxic state. NeuroImage. 245:Article 118769. https://doi.org/10.1016/j.neuroimage.2021.118769

Atucha E, Ku S-P, Lippert M, Sauvage M. 2021. Remembering the gist of an event over a lifetime depends on the hippocampus. bioRxiv. https://doi.org/10.1101/2021.04.14.439803

Crittenden JR, Zhai S, Sauvage M, Kitsukawa T, Burguière E, Thomsen M, Zhang H, Costa C, Martella G, Ghiglieri V, et al. 2021. CalDAG-GEFI mediates striatal cholinergic modulation of dendritic excitability, synaptic plasticity and psychomotor behaviors. Neurobiology of Disease. 158:Article 105473. https://doi.org/10.1016/j.nbd.2021.105473

Grande X, Sauvage M, Becke A, Düzel E, Berron D. 2021. Functional connectivity and information pathways in the human entorhinal-hippocampal circuitry. (bioRxiv). https://doi.org/10.1101/2021.12.17.473123

Henschke JU, Price AT, Pakan JMP. 2021. Enhanced modulation of cell-type specific neuronal responses in mouse dorsal auditory field during locomotion. Cell calcium. 96:Article 102390. https://doi.org/10.1016/j.ceca.2021.102390

Ku S-P, Hargreaves EL, Wirth S, Suzuki WA. 2021. The contributions of entorhinal cortex and hippocampus to error driven learning. Communications biology. 4(1):Article 618. https://doi.org/10.1038/s42003-021-02096-z

Mahnke L, Atucha E, Pina-Fernàndez E, Kitsukawa T, Sauvage MM. 2021. Lesion of the hippocampus selectively enhances LEC's activity during recognition memory based on familiarity. Scientific Reports. 11(1):Article 19085. https://doi.org/10.1038/s41598-021-98509-4

Oulé M, Atucha E, Wells TM, Macharadze T, Sauvage MM, Kreutz MR, Lopez-Rojas J. 2021. Dendritic Kv4.2 potassium channels selectively mediate spatial pattern separation in the dentate gyrus. iScience. 24(8):102876. https://doi.org/10.1016/j.isci.2021.102876

Valero-Aracama MJ, Reboreda A, Arboit A, Sauvage M, Yoshida M. 2021. Noradrenergic suppression of persistent firing in hippocampal CA1 pyramidal cells through cAMP-PKA pathway. eNeuro. 8(2):1-12. https://doi.org/10.1523/ENEURO.0440-20.2020

2020

Arboit A, Reboreda A, Yoshida M. 2020. Involvement of TRPC4 and 5 Channels in Persistent Firing in Hippocampal CA1 Pyramidal Cells. Cells. 9(2):Article 365. https://doi.org/10.3390/cells9020365

Kessler H, Schmidt AC, James EL, Blackwell SE, von Rauchhaupt M, Harren K, Kehyayan A, Clark IA, Sauvage M, Herpertz S, et al. 2020. Visuospatial computer game play after memory reminder delivered three days after a traumatic film reduces the number of intrusive memories of the experimental trauma. Journal of Behavior Therapy and Experimental Psychiatry. 67:Article 101454. https://doi.org/10.1016/j.jbtep.2019.01.006

Mahnke L, Atucha E, Kitsukawa T, Sauvage MM. 2020. Recognition memory: familiarity signals increase selectively in the lateral entorhinal cortex following hippocampal lesions. bioRxiv. https://doi.org/10.1101/2020.06.16.131763

Rivas-Ramírez P, Reboreda A, Rueda-Ruzafa L, Herrera-Pérez S, Lamas JA. 2020. Contribution of KCNQ and TREK Channels to the Resting Membrane Potential in Sympathetic Neurons at Physiological Temperature. International Journal of Molecular Sciences. 21(16):1-16. https://doi.org/10.3390/ijms21165796

2019

Knauer B, Yoshida M. 2019. Switching between persistent firing and depolarization block in individual rat CA1 pyramidal neurons. Hippocampus. 29(9):817-835. https://doi.org/10.1002/hipo.23078

Krautwald K, Mahnke L, Angenstein F. 2019. Electrical Stimulation of the Lateral Entorhinal Cortex Causes a Frequency-Specific BOLD Response Pattern in the Rat Brain. Frontiers in Neuroscience. 13(MAY):Article 539. https://doi.org/10.3389/fnins.2019.00539

Sauvage M, Kitsukawa T, Atucha E. 2019. Single-cell memory trace imaging with immediate-early genes. Journal of Neuroscience Methods. 326:108368. https://doi.org/10.1016/j.jneumeth.2019.108368

Crittenden J., Sauvage M, Kitsukawa T, Burguière E, Cepeda C, André VM, Canault M, Thomsen M, Zhang H, Costa C, Martella G, Ghiglieri V, Pescatore KA, Unterwald EM, Jackson W, Housman DE, Caine SB, Sulzer D, Calabresi P, Levine MS, Brefel-Courbon C,  Smith AC, Alessi MC, Azulay JP, Graybiel AM. 2019. Mutations in CalDAG-GEFI Lead to Striatal Signaling Deficits and Psychomotor Symptoms in Multiple Species Including Human. https://www.biorxiv.org/content/10.1101/709246v1

2018

Beer Z, Vavra P, Atucha E, Rentzing K, Heinze HJ, Sauvage MM. 2018. The memory for time and space differentially engages the proximal and distal parts of the hippocampal subfields CA1 and CA3. PLoS Biology. 16(8):e2006100. https://doi.org/10.1371/journal.pbio.2006100

Behroozi M, Chwiesko C, Ströckens F, Sauvage M, Helluy X, Peterburs J, Güntürkün O. 2018. In vivo measurement of T₁ and T₂ relaxation times in awake pigeon and rat brains at 7T. Magnetic Resonance in Medicine. 79(2):1090-1100. https://doi.org/10.1002/mrm.26722

Berron D, Neumann K, Maass A, Schütze H, Fliessbach K, Kiven V, Jessen F, Sauvage M, Kumaran D, Düzel E. 2018. Age-related functional changes in domain-specific medial temporal lobe pathways. Neurobiology of Aging. 65:86-97. https://doi.org/10.1016/j.neurobiolaging.2017.12.030

Fernández-Fernández D, Cadaveira-Mosquera A, Rueda-Ruzafa L, Herrera-Pérez S, Veale EL, Reboreda A, Mathie A, Antonio Lamas J. 2018. Activation of TREK currents by riluzole in three subgroups of cultured mouse nodose ganglion neurons. PLoS ONE. 13(6). https://doi.org/10.1371/journal.pone.0199282

Flasbeck V, Atucha E, Nakamura NH, Yoshida M, Sauvage MM. 2018. Spatial information is preferentially processed by the distal part of CA3: implication for memory retrieval. Behavioural Brain Research. 354:31-38. https://doi.org/10.1016/j.bbr.2018.07.023

Reboreda A, Theissen FM, Valero-Aracama MJ, Arboit A, Corbu MA, Yoshida M. 2018. Do TRPC channels support working memory? Comparing modulations of TRPC channels and working memory through G-protein coupled receptors and neuromodulators. Behavioural Brain Research. 354:64 - 83. https://doi.org/10.1016/j.bbr.2018.02.042

2017

Atucha E, Karew A, Kitsukawa T, Sauvage MM. 2017. Recognition memory: Cellular evidence of a massive contribution of the LEC to familiarity and a lack of involvement of the hippocampal subfields CA1 and CA3. Hippocampus. 27(10):1083-1092. https://doi.org/10.1002/hipo.22754

Atucha E, Vukojevic V, Fornari RV, Ronzoni G, Demougin P, Peter F, Atsak P, Coolen MW, Papassotiropoulos A, McGaugh JL, de Quervain DJF, Roozendaal B. 2017. Noradrenergic activation of the basolateral amygdala maintains hippocampus-dependent accuracy of remote memory. Proceedings of the National Academy of Sciences of the United States of America. 114(34):9176-9181. https://doi.org/10.1073/pnas.1710819114

Cutsuridis V, Yoshida M. 2017. Editorial: Memory processes in medial temporal lobe: Experimental, theoretical and computational approaches. Frontiers in Systems Neuroscience. 11:Article 19. https://doi.org/10.3389/fnsys.2017.00019

Giovannini F, Knauer B, Yoshida M, Buhry L. 2017. The CAN-In network: A biologically inspired model for self-sustained theta oscillations and memory maintenance in the hippocampus. Hippocampus. 27(4):450-463. https://doi.org/10.1002/hipo.22704

Ku SP, Nakamura NH, Maingret N, Mahnke L, Yoshida M, Sauvage MM. 2017. Regional specific evidence for memory-load dependent activity in the dorsal subiculum and the lateral entorhinal cortex. Frontiers in Systems Neuroscience. 11:Article 51. https://doi.org/10.3389/fnsys.2017.00051

Lux V, Masseck OA, Herlitze S, Sauvage MM. 2017. Optogenetic Destabilization of the Memory Trace in CA1: Insights into Reconsolidation and Retrieval Processes. Cerebral Cortex. 27(1):841-851. https://doi.org/10.1093/cercor/bhv282

2016

Hamburg H, Trossbach SV, Bader V, Chwiesko C, Kipar A, Sauvage M, Crum WR, Vernon AC, Bidmon HJ, Korth C. 2016. Simultaneous effects on parvalbumin-positive interneuron and dopaminergic system development in a transgenic rat model for sporadic schizophrenia. Scientific Reports. 6:Article 34946. https://doi.org/10.1038/srep34946

Lux V, Atucha Trevino E, Kitsukawa T, Sauvage MM. 2016. Imaging a memory trace over half a life-time in the medial temporal lobe reveals a time-limited role of CA3 neurons in retrieval. eLife. 5(FEBRUARY2016):Article e11862. https://doi.org/10.7554/eLife.11862

Nakamura NH, Sauvage MM. 2016. Encoding and reactivation patterns predictive of successful memory performance are topographically organized along the longitudinal axis of the hippocampus. Hippocampus. 26(1):67-75. https://doi.org/10.1002/hipo.22491

Trossbach SV, Bader V, Hecher L, Pum ME, Masoud ST, Prikulis I, Schäble S, de Souza Silva MA, Su P, Boulat B, Chwiesko C, Poschmann G, Stühler K, Lohr KM, Stout KA, Oskamp A, Godsave SF, Müller-Schiffmann A, Bilzer T, Steiner H, Peters PJ, Bauer A, Sauvage M, Ramsey AJ, Miller GW, Liu F, Seeman P, Brandon NJ, Huston JP, Korth C. 2016. Misassembly of full-length Disrupted-in-Schizophrenia 1 protein is linked to altered dopamine homeostasis and behavioral deficits. Molecular Psychiatry. 21(11):1561-1572. https://doi.org/10.1038/mp.2015.194

Yoshida M. 2016. Mechanisms and Roles of Intrinsic Persistent Firing in the Hippocampus. Seibutsu Butsuri. 56(5). https://doi.org/10.2142/biophys.56.262

2015

Jochems A, Yoshida M. 2015. A robust in vivo-like persistent firing supported by a hybrid of intracellular and synaptic mechanisms. PLoS ONE. 10(4):Article e0123799. https://doi.org/10.1371/journal.pone.0123799

Kabanova A, Pabst M, Lorkowski M, Braganza O, Boehlen A, Nikbakht N, Pothmann L, Vaswani AR, Musgrove R, Di Monte DA, Sauvage M, Beck H, Blaess S. 2015. Function and developmental origin of a mesocortical inhibitory circuit. Nature Neuroscience. 18(6):872-882. https://doi.org/10.1038/nn.4020

Saravanan V, Arabali D, Jochems A, Cui AX, Gootjes-Dreesbach L, Cutsuridis V, Yoshida M. 2015. Transition between encoding and consolidation/replay dynamics via cholinergic modulation of CAN current: A modeling study. Hippocampus. 25(9):1052-1070. https://doi.org/10.1002/hipo.22429

Valero-Aracama MJ, Sauvage MM, Yoshida M. 2015. Environmental enrichment modulates intrinsic cellular excitability of hippocampal CA1 pyramidal cells in a housing duration and anatomical location-dependent manner. Behavioural Brain Research. 292:209-218. https://doi.org/10.1016/j.bbr.2015.05.032

2014

Beer Z, Chwiesko C, Sauvage MM. 2014. Processing of spatial and non-spatial information reveals functional homogeneity along the dorso-ventral axis of CA3, but not CA1. Neurobiology of Learning and Memory. 111:56-64. https://doi.org/10.1016/j.nlm.2014.03.001

Herold C, Bingman VP, Ströckens F, Letzner S, Sauvage M, Palomero-Gallagher N, Zilles K, Güntürkün O. 2014. Distribution of neurotransmitter receptors and zinc in the pigeon (Columba livia) hippocampal formation: A basis for further comparison with the mammalian hippocampus. Journal of Comparative Neurology. 522(11):2553-2575. https://doi.org/10.1002/cne.23549

Wiemers US, Sauvage MM, Wolf OT. 2014. Odors as effective retrieval cues for stressful episodes. Neurobiology of Learning and Memory. 112:230-236. https://doi.org/10.1016/j.nlm.2013.10.004

2013

Beer Z, Chwiesko C, Kitsukawa T, Sauvage MM. 2013. Spatial and stimulus-type tuning in the LEC, MEC, POR, PrC, CA1, and CA3 during spontaneous item recognition memory. Hippocampus. 23(12):1425-1438. https://doi.org/10.1002/hipo.22195

Nakamura NH, Flasbeck V, Maingret N, Kitsukawa T, Sauvage MM. 2013. Proximodistal segregation of nonspatial information in CA3: Preferential recruitment of a proximal CA3-distal CA1 network in nonspatial recognition memory. Journal of Neuroscience. 33(28):11506-11514. https://doi.org/10.1523/JNEUROSCI.4480-12.2013

Sauvage MM, Nakamura NH, Beer Z. 2013. Mapping memory function in the medial temporal lobe with the immediate-early gene Arc. Behavioural Brain Research. 254:22-33. https://doi.org/10.1016/j.bbr.2013.04.048

Wiemers US, Sauvage MM, Schoofs D, Hamacher-Dang TC, Wolf OT. 2013. What we remember from a stressful episode. Psychoneuroendocrinology. 38(10):2268-2277. https://doi.org/10.1016/j.psyneuen.2013.04.015

2012

Eichenbaum H, Sauvage M, Fortin N, Komorowski R, Lipton P. 2012. Towards a functional organization of episodic memory in the medial temporal lobe. Neuroscience and Biobehavioral Reviews. 36(7):1597-1608. https://doi.org/10.1016/j.neubiorev.2011.07.006

Eichenbaum H, Sauvage M, Fortin N, Robitsek J, Komorowski R. 2012. A Comparative Analysis of Episodic Memory: Cognitive Mechanisms and Neural Substrates. In The Oxford Handbook of Comparative Cognition. Oxford University Press. https://doi.org/10.1093/oxfordhb/9780195392661.013.0017

Place R, Lykken C, Beer Z, Suh J, McHugh TJ, Tonegawa S, Eichenbaum H, Sauvage MM. 2012. NMDA signaling in CA1 mediates selectively the spatial component of episodic memory. Learning and Memory. 19(4):164-169. https://doi.org/10.1101/lm.025254.111

Sauvage MM. 2012. Neural substrates of recollection and familiarity: Further bridging human and animal recognition memory using translational paradigms. In Psychology of Memory. Nova Science Publishers, Inc. pp. 155-182.

2010

Eichenbaum H, Fortin N, Sauvage M, Robitsek RJ, Farovik A. 2010. An animal model of amnesia that uses Receiver Operating Characteristics (ROC) analysis to distinguish recollection from familiarity deficits in recognition memory. Neuropsychologia. 48(8):2281-2289. https://doi.org/10.1016/j.neuropsychologia.2009.09.015

Sauvage MM, Beer Z, Eichenbaum H. 2010. Recognition memory: Adding a response deadline eliminates recollection but spares familiarity. Learning and Memory. 17(2):104-108. https://doi.org/10.1101/lm.1647710

Sauvage MM, Beer Z, Ekovich M, Ho L, Eichenbaum H. 2010. The caudal medial entorhinal cortex: A selective role in recollection-based recognition memory. Journal of Neuroscience. 30(46):15695-15699. https://doi.org/10.1523/JNEUROSCI.4301-10.2010

Sauvage MM. 2010. ROC in animals: Uncovering the neural substrates of recollection and familiarity in episodic recognition memory. Consciousness and Cognition. 19(3):816-828. https://doi.org/10.1016/j.concog.2010.06.023

International/National

• Dr. Susumu Tonegawa (MIT/RIKEN, USA)
• Dr. Jozsef Csicsvari (IST, Austria),
• Dr. Takashi Kitsukawa (Osaka University, Japan)
• Prof. Dr. Kitamura (Northwestern U, USA)
• Prof. Dr. Mathias Hoehn (MPI for Neurological Research, Cologne)
• Prof. Dr. Stephan Herpertz (Medical Faculty, LWL, Clinic for Psychosomatic Medicine and Psychotherapy, Bochum)
• Dr. Andrew Yonelinas (UCDavis, USA)
• Prof. Dr. Dr. Onur Güntürkün and Prof. Dr. Boris Suchan (Faculty of Psychology, RUB, Germany)
• Prof. Dr. Michael Yassa (Irvine, USA)
• Dr. Sheena Josselyn (Sickkids, Toronto, Canada)

Lokal:

• Prof. Dr. Emrah Düzel (DZNE)
• Prof. Dr. Frank Angenstein (DZNE)
• Dr. Eike Budinger (LIN)
• Dr. Motoharu Yoshida (LIN/DZNE)