Patterning to enhance activity of cultured neuronal networks.

Embryonic rat hippocampal neurons were cultured in order to gain insights into how small networks of neurons interact. The principal observations are the electrical activities recorded with the electrode arrays, primarily action potentials both spontaneous and evoked. Several lithographic techniques were developed for controlling with micrometer precision the patterns of surface molecules in order to control neuronal attachment and growth. Cytophilic polylysine against protein repellent and hence cytophobic polyethylene glycol were used. By combining the cellular lithography with the microelectrode arrays it was possible to guide neurons preferentially to electrodes and to begin to investigate the question as to whether the geometric pattern of a neuronal network influences the patterns of its neuroelectric activity. It is clear that the techniques are adequate to ensure contact of neurons to electrodes but not to ensure the recording of signals, even when neurons lie directly on top of electrodes. The maturation of neuroelectric activity depends on the growth of glia within the culture, such that spontaneous activity appears to become robust when the number of glia is roughly the same as the number of neurons.