Impaired hippocampal representation of place in the Fmr1-knockout mouse model of fragile X syndrome.
Tara ArbabCyriel M A PennartzFrancesco P BattagliaPublished in: Scientific reports (2018)
Fragile X syndrome (FXS) is an X-chromosome linked intellectual disability and the most common known inherited single gene cause of autism spectrum disorder (ASD). Building upon demonstrated deficits in neuronal plasticity and spatial memory in FXS, we investigated how spatial information processing is affected in vivo in an FXS mouse model (Fmr1-KO). Healthy hippocampal neurons (so-called place cells) exhibit place-related activity during spatial exploration, and their firing fields tend to remain stable over time. In contrast, we find impaired stability and reduced specificity of Fmr1-KO spatial representations. This is a potential biomarker for the cognitive dysfunction observed in FXS, informative on the ability to integrate sensory information into an abstract representation and successfully retain this conceptual memory. Our results provide key insight into the biological mechanisms underlying cognitive disabilities in FXS and ASD, paving the way for a targeted approach to remedy these.
Keyphrases
- autism spectrum disorder
- intellectual disability
- mouse model
- attention deficit hyperactivity disorder
- working memory
- induced apoptosis
- cerebral ischemia
- traumatic brain injury
- case report
- spinal cord
- magnetic resonance
- copy number
- cell cycle arrest
- magnetic resonance imaging
- gene expression
- genome wide
- healthcare
- neural network
- blood brain barrier
- oxidative stress
- transcription factor
- mass spectrometry
- endoplasmic reticulum stress
- single molecule