Here we sought to develop a microfluidic device or chamber optimized for synaptic cell biology that allows one to visualize and manipulate synapses and pre- and postsynaptic cell bodies independently. Until now, this has not been possible using other compartmentalized methods, including microfluidic methods. To accomplish this goal, we adapted a previously developed compartmentalized microfluidic chamber used to direct the growth of cortical and hippocampal axons through parallel microgrooves (Taylor et al., 2005; Taylor et al., 2003). Our first goal was to direct the growth of dendrites into microgrooves and verify that functional synapses were formed within the microfluidic chamber when two populations of neurons were grown on either side of the microgrooves. Second, we implemented a small perfusion channel to locally perturb and investigate synaptic regions with high spatial and temporal resolution. As proof of principle, we demonstrate the utility of this chamber to investigate synapse-to-nucleus signaling in multiple ways– using calcium imaging, comparing transcriptional responses to spaced and massed stimulation, and investigating changes in Arc transcription and mRNA localization following the local application of the mGluR1 group I agonist, DHPG.
