Neural correlates of memory impairment and rescue in a mouse model of down syndrome
Year: 2019
Type: dissertation
Abstract: Understanding the neural correlates of intellectual disability is still a central and unresolved problem in neuroscience. Here we have unravelled several candidate neural substrates of memory impairment and rescue using a mouse model of Down syndrome and three pro-cognitive strategies: epigallocatechin-3-galate (EGCG), environmental enrichment (EE) and α5IA. We recorded neural activity simultaneously from the prefrontal cortex (PFC) and hippocampus (HPC) of trisomic Ts65Dn and healthy mice during quiet wakefulness, natural sleep and the novel object recognition task. Trisomic mice showed recognition memory deficits that were accompanied by hypersynchronised neural activity in the PFC and HPC, exaggerated PFC-HPC functional connectivity and ripple alterations that predicted poor memory performance. We also identified in healthy mice that memory acquisition depends on PFC-to-HPC theta connectivity whereas memory retrieval depends on HPC-to-PFC low gamma connectivity. Both memory biomarkers predicted memory performance, were disrupted in trisomic mice and rescued by EGCG and EE. Collectively, we identified unique neurophysiological biomarkers that are candidate cellular mechanisms underlying intellectual disability in DS.
Authors: Alemany González, Maria Fragaki
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2967792393