Fetal rat brains that have been mechanically dissociated into single cells will reassociate to form spherical reaggregates when placed in culture on a gyratory shaker. Extracellular recordings from these reaggregates indicate that they exhibit spontaneous bioelectric activity, which is occasionally rhythmic. Bioelectric activity of maximal amplitude is observed just beneath the reaggregate surface, and the sign of this activity often reverses upon deeper penetration by the microelectrode. The average amplitude of the spontaneous discharge is reduced by addition of Mg2+ and Mn2+, but lowering the concentration of Na+ or addition of tetrodotoxin increase the discharge amplitudes. It is suggested that Ca2+ mediates the electrical activity, and that the rhythm is partially autogenic in origin. In addition, agents which synaptically block the inhibitory neurotransmitters γ-aminobutyrate and glycine enhance the spontaneous activity, as does the convulsant pentylenetetrazol. A mechanism of excitation through the release of inhibition, utilizing a decrease in chloride conductance, is proposed. These reaggregate cultures exhibit a developmental sequence of electrophysiological changes which parallel those demonstrated biochemically and morphologically, and should prove useful for studying nervous system development.
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