Development of neuronal timescales in human cortical organoids and rat hippocampus dissociated cultures.

ABSTRACT

To support complex cognition, neuronal circuits must integrate information across multiple temporal scales, ranging from milliseconds to decades. Neuronal timescales describe the duration over which activity within a network persists, posing a putative explanatory mechanism for how information might be integrated over multiple temporal scales. Little is known about how timescales develop in human neural circuits or other model systems, limiting insight into how the functional dynamics necessary for cognition emerge. In our work, we show that neuronal timescales develop in a non-linear fashion in both human cortical organoids and dissociated rat hippocampus cultures. We use spectral parameterization of spiking activity to extract an estimate of neuronal timescale that is unbiased by co-evolving oscillations. Cortical organoid timescales begin to increase around month 6 post-differentiation. We complement these findings with an analysis of timescales in rodent hippocampal dissociated cultures over development and see that timescales decrease from in vitro days 13-23 before stabilizing. We speculate that cortical organoid development over the duration studied here reflects an earlier stage of a generalized developmental timeline in contrast to the rodent hippocampal cultures, potentially accounting for differences in timescale developmental trajectories. The fluctuation of timescales might be an important developmental feature that reflects the changing complexity and information capacity in developing neuronal circuits.