Der Zusammenhang zwischen funktioneller Vielfalt bei CA1 Pyramidenzellen und ihrem embryonalen Entwicklungszeitpunkt im Hippokampus der Maus in vivo
Anatomie und Physiologie
Zusammenfassung der Projektergebnisse
The hippocampus is known to be substantial for episodic and declarative memory. During memory performances, an ordered co-activation of neurons (sequences) was described manifold and the following reactivation of these sequences during the awake resting state or sleep was proven to be crucial for memory performance. The awake reactivation is often associated with sharp-wave ripples, a high-frequency population burst (180-220 Hz), and has been shown to support encoding, consolidation and retrieval of event memories as well as guiding memory-guided decision-making. All of these studies used electrophysiological approaches which do not allow a precise recognition of a specific neuron, especially not over consecutive days. We used calcium imaging in vivo (optical detection of neuronal activity) to map patterns of synchronous neuronal activation in the CA1 region of awake mice running on a treadmill distinguishing between run-related coactivity and sharp-wave ripple associated activity (SPW-R). So far, the organization and lifetime of these coactive neurons (assemblies) remains unknown and our investigation adds profound information about the network organization of memory and its rigidity or failures. I discovered that SPW-R associated events (SCE) fall into three distinct categories. Most of them recruit neurons coming from a finite repertoire of preconfigured anatomically intermingled cell assemblies. The activity of neurons between e.g. two different assemblies are mutually exclusive, mathematically speaking “orthogonal”, and reactivated discrete temporal segments of neuronal sequences observed during run. They can be stable across days whereby up to 40% of cells pairs rather re-activate in the same assembly from one day to the next than mingling with others. Additionally, prolonged activation phases binding different assemblies into longer chains revealed temporally ordered replay of previous running experience of the mouse. Multiple-assembly SCEs preferentially bind these assemblies into the replay of ongoing internal dynamics on a compressed time scale, as described electrophysiological for the extended replay phenomenon. These modules may therefore represent the default building blocks or attractor states to encode or retrieve experience. Furthermore, I obtained a dataset to rule out if a developmental factor might lead this process. It is clear that the recently described differences in rigid and flexible learned hippocampal sequences are important especially considering memory distortions and inaccuracies related to age (e.g. false memories or deleterious illnesses such as Alzheimers, epilepsy, chronic stress and neurodegeneration. Finally, the understanding of single cell behavior, plasticity dependent assemblies formation should answer the question how we can enhance resilience, regeneration and restoration of the hippocampal network and could lead to therapeutic interventions on a cellular and systems level in mental diseases.
Projektbezogene Publikationen (Auswahl)
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GABAergic inhibition shapes interictal dynamics in awake epileptic mice. In: Brain (2015) Oct;138(Pt 10):2875-90
Muldoon SF, Villette V, Tressard T, Malvache A, Reichinnek S, Bartolomei F, Cossart R
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Awake hippocampal reactivations project onto orthogonal neuronal assemblies. In: Science 16 Sep 2016, Vol. 353, Issue 6305, pp. 1280-1283
Malvache M, Reichinnek S, Villette V, Haimerl C and Cossart R
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Image-based adaptive optics for in vivo imaging in the hippocampus. Scientific Reports volume 7, Article number: 42924 (2017)
D. Champelovier, J. Teixeira, J-M. Conan, N. Balla, L. Mugnier, T. Tressard, S. Reichinnek, S. Meimon, R. Cossart, H. Rigneault, S. Monneret, A. Malvache
