Our new paper lead by Stephanie Prince is published and featured on the cover of Cell Reports. We found weaker inhibitory synaptic connections onto pyramidal neurons in CA1 during navigation in a mouse model of Alzheimer’s disease. Synaptic dysfunction is thought key to memory impairment in Alzheimer’s disease but is typically studied in slice or in post-mortem tissue even though synaptic and neural activity are very different in vivo during behavior. Surprisingly deficits in inhibitory synapses in AD mice were strongest during sharp-wave ripples when replay or reactivation of prior experiences normally occurs in healthy mice. Sharp wave ripple reactivation is like hitting the replay button for your brain and it is essential for normal spatial memory. We found this reactivation is drastically reduced in the Alzheimer’s mouse model, likely due to these impaired inhibitory synapses. These findings bridge Alzheimer’s dysfunction from synaptic deficits in vivo during navigation to neural activity failures to memory processes. Cover art by Annie Stuart. https://www.cell.com/cell-reports/fulltext/S2211-1247(21)00322-3
