Silencing synapses: a route to understanding synapse degeneration in chronic neurodegenerative disease

The degeneration of pre-synaptic boutons in the stratum radiatum of the dorsal hippocampus is one of earliest components of neurodegeneration in several models of murine prion disease. We recently showed that blockade of synaptic transmission by infusion of botulinum neurotoxin A (BoNT/A) into the hippocampus several weeks prior to the onset of degeneration, had no detectable impact on the extent of the synaptic degeneration. ( 1) We elaborate here on the rationale for these experiments and highlight why we believe that this negative result is interesting and important. We also discuss new observations that might provide insights into the molecular events that underlie synapse degeneration.