Sleep-dependent formation of memory
Tuesday, 29 March 2022, 16:00, online via Zoom
Prof. Dr. Jan Born
Institute of Medical Psychology and Behavioral Neurobiology, University of Tübingen, Germany
Whereas memories are optimally encoded and retrieved when the brain is awake, the consolidation and formation of long-term memory requires an offline mode of processing as optimally established only during sleep. Based on evidence from behavioral and neurobiological studies in humans and rodents, I will consider the formation of long-term memory during sleep as an “active systems consolidation” process in which the repeated neuronal replay of representations originating from the hippocampus during slow-wave sleep (SWS) leads to a gradual transformation and integration of representations in extrahippocampal, mainly neocortical networks. I will highlight three features of this process: (i) Hippocampal replay that, by capturing episodic memory aspects, drives consolidation of both hippocampus-dependent and non-hippocampus-dependent memory; (ii) brain oscillations hallmarking SWS and rapid-eye movement (REM) sleep, respectively, which provide mechanisms to regulate both information flow across distant brain networks and local synaptic plasticity; and (iii) qualitative transformations of memories during sleep-dependent systems consolidation resulting in abstract schema-like representations. Here, I will emphasize the importance of sleep for memory transformation during early development.
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Pathogenic mechanisms of Niemann Pick C disease: altered neuronal and glial cell differentiation largely anticipates overt neurologic dysfunction
Friday, 08 April 2022, 11:00, Hörsaal der Anatomie (Hybrid), Zoom
Maria Teresa Fiorenza, PhD, Associate Professor of Applied Neurobiology,
Division of Neuroscience, Faculty of Medicine and Psychology, Sapienza University of Rome, Italy; European Center for Brain Research
The Niemann Pick type C disease (NPCD) is a rare inherited neurodegenerative lysosomal storage disorder caused by genetic loss-of-function mutations of the endolysosomal cholesterol exporters NPC1 (95% of clinical cases) or NPC2 (5%). However, lysosomal cholesterol engorgement has never fully explained the complex manifestation of NPCD.Over recent years, using NPCD mouse models we have provided compelling evidence that the defective mobilization of intracellular cholesterol deranges the proliferation and differentiation of neuronal and glial cells within the postnatal developing cerebellum and olfactory bulb. In both these areas, the occurrence of developmental events under a protracted condition of defective intracellular cholesterol mobilization hits the functional maturation of the various cell types, predisposing to the appearance of cellular alterations and clinical signs.Hence, we have demonstrated that cholesterol dyshomeostasis in NPC affects Shh-mediated signaling, at the primary cilium, impairing the differentiation and functional maturation of neurons and glial cells and causing a delay in the acquisition of complex motor abilities by prepuberal Npc1-deficient mice compared to wt littermates.More recently, we have found that the production of postnatal-born neuroblasts in the SVZ is reduced and their integration in the granule cell layer of the olfactory bulb is defective in young-adult Npc1-deficient mice. This associates with a significant increase of activated microglia engaged in phagocytic activity, which reasonably represents an indirect sign of altered maturation of newly generated granule neurons. This possibility is strengthened by the presence of shortfalls in fine odor discrimination ability, which anticipates major olfactory dysfunction of NPC disease mouse model. All together our findings favor the view that the occurrence of developmental defects in affected patients should be thoughtfully considered to secure a more exhaustive comprehension of the disease.