Building and manipulating neural pathways with microfluidics

Communication between different brain regions, and between local circuits in the same brain region, is an important area of study for basic and translational neuroscience research. Selective and chronic manipulation of one of the components in a given neural pathway is frequently required for development and plasticity studies. We designed an in vitro platform that captures some of the complexity of mammalian brain pathways but permits easy experimental manipulation of their constituent parts. Organotypic cultures of brain slices were carried out in compartments interconnected by microchannels. We show that co-cultures from cortex and hippocampus formed functional connections by extending axons through the microchannels. We report synchronization of neural activity in co-cultures, and demonstrate selective pharmacological manipulation of activity in the constituent slices. Our platform enables chronic, spatially-restricted experimental manipulation of pre- and post-synaptic neurons in organotypic cultures, and will be useful to investigators seeking to understand development, plasticity, and pathologies of neural pathways.