Deep sequencing and high resolution imaging reveals the local transcriptome in the hippocampal synaptic neuropil

It is clear that de novo protein synthesis plays an important role in synaptic transmission and plasticity. Previous studies have demonstrated that mRNA translation is spatially controlled and that dendritic protein synthesis is required for different forms of long-term synaptic plasticity. Yet, the population of mRNAs that are localized to dendrites remain sparsely identified. Here we use deep sequencing to identify the mRNAs resident in the synaptic neuropil of the CA1 area of the hippocampus. Analysis of a neuropil dataset yielded a list of ~8000 transcripts of which ~2600 are localized in dendrites and/or axons. Using a new fluorescent barcode strategy to label individual mRNAs, we show that their relative abundance in the neuropil varies over 3 orders of magnitude. mRNAs for a large fraction of known synaptic proteins were also detected- dramatically expanding the potential for local translation. Induction of synaptic plasticity that requires local translation resulted in an increase in the dendritic mRNA population. These results reveal a previously unappreciated enormous potential for the local protein synthesis machinery to supply, maintain and modify the dendritic and synaptic proteome.