Ultrastructural Evidence for a Role of Astrocytes and Glycogen-Derived Lactate in Learning-Dependent Synaptic Stabilization
| Autor: | Mariaelvina Sala, Dominique Muller, Nicolas Gagnon, Pierre J. Magistretti, Andrea Falqui, Corrado Calì, Elisa Sogne, Daniela Braida, Maura Francolini, Elena Vezzoli, M. De Roo, Luisa Ponzoni |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
Cognitive Neuroscience Hippocampal formation glycogen metabolism Hippocampus 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound Mice 0302 clinical medicine long-term memory Organ Culture Techniques In vivo Animals Learning Lactic Acid 030304 developmental biology 0303 health sciences lactate synaptic plasticity Glycogen Long-term memory Long-term potentiation 3D electron microscopy Cell biology Mice Inbred C57BL chemistry Astrocytes Synaptic plasticity Synapses Ultrastructure Original Article Postsynaptic density 030217 neurology & neurosurgery |
| Zdroj: | Cerebral Cortex (New York, NY) |
| Popis: | Long-term memory formation (LTM) is a process accompanied by energy-demanding structural changes at synapses and increased spine density. Concomitant increases in both spine volume and postsynaptic density (PSD) surface area have been suggested but never quantified in vivo by clear-cut experimental evidence. Using novel object recognition in mice as a learning task followed by 3D electron microscopy analysis, we demonstrate that LTM induced all aforementioned synaptic changes, together with an increase in the size of astrocytic glycogen granules, which are a source of lactate for neurons. The selective inhibition of glycogen metabolism in astrocytes impaired learning, affecting all the related synaptic changes. Intrahippocampal administration of l-lactate rescued the behavioral phenotype, along with spine density within 24 hours. Spine dynamics in hippocampal organotypic slices undergoing theta burst-induced long-term potentiation was similarly affected by inhibition of glycogen metabolism and rescued by l-lactate. These results suggest that learning primes astrocytic energy stores and signaling to sustain synaptic plasticity via l-lactate. |
| Databáze: | OpenAIRE |
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