Abstract
Down syndrome, the leading genetic cause of intellectual disability, results from an extra-copy of chromosome 21. Mice engineered to model this aneuploidy exhibit Down syndrome-like memory deficits in spatial and contextual tasks. While abnormal neuronal function has been identified in these models, most studies have relied on in vitro measures. Here, using in vivo recording in the Dp(16)1Yey model, we find alterations in the organization of spiking of hippocampal CA1 pyramidal neurons, including deficits in the generation of complex spikes. These changes lead to poorer spatial coding during exploration and less coordinated activity during sharp-wave ripples, events involved in memory consolidation. Further, the density of CA1 inhibitory neurons expressing neuropeptide Y, a population key for the generation of pyramidal cell bursts, were significantly increased in Dp(16)1Yey mice. Our data refine the 'over-suppression' theory of Down syndrome pathophysiology and suggest specific neuronal subtypes involved in hippocampal dysfunction in these model mice.
Highlights
Down syndrome (DS), with an incidence of one in 700 to 1000 live births, is the most common genetic cause of intellectual disability (Parker et al, 2010)
In order to investigate hippocampal spatial coding Dp(16)1Yey (Dp16; N = 6) and wild-type littermate control (WT; N = 5) mice were implanted with recording electrodes in the dorsal CA1 pyramidal cell layer and allowed to explore a linear track (Figure 1A)
CA1 pyramidal neurons in these mice showed a significant decrease in ability to burst and produce complex spikes, and while their phase locking to theta oscillations was conserved, spatial encoding and information content was significantly lower
Summary
Down syndrome (DS), with an incidence of one in 700 to 1000 live births, is the most common genetic cause of intellectual disability (Parker et al, 2010). Accumulating data, support the idea that a shift in the balance between inhibitory and excitatory transmission may contribute to DS learning phenotypes, in the hippocampus (Kleschevnikov et al, 2012; Kleschevnikov et al, 2004). This has led to the proposal that targeting alterations in GABAergic signaling may be a viable therapeutic target (Contestabile et al, 2017), evidence for this on the circuit level is scarce
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
