State-Dependent Propagation of Neuronal Sub-Population in Spontaneous Synchronized Bursts

Abstract

Repeating stable spatiotemporal patterns emerge in synchronized spontaneous activity in neuronal networks. The repertoire of such patterns can serve as memory, or a reservoir of information, in a neuronal network; moreover, the variety of patterns may represent the network memory capacity. However, a neuronal substrate for producing a repertoire of patterns in synchronization remains elusive. We herein hypothesize that state-dependent propagation of a neuronal sub-population is the key mechanism. By combining high-resolution measurement with a 4096-channel complementary metal-oxide semiconductor (CMOS) microelectrode array (MEA) and dimensionality reduction with non-negative matrix factorization (NMF), we investigated synchronized bursts of dissociated rat cortical neurons at approximately 3 weeks in vitro. We found that bursts had a repertoire of repeating spatiotemporal patterns, and different patterns shared a partially similar sequence of sub-population, supporting the idea of sequential structure of neuronal sub-populations during synchronized activity. We additionally found that similar spatiotemporal patterns tended to appear successively and periodically, suggesting a state-dependent fluctuation of propagation, which has been overlooked in existing literature. Thus, such a state-dependent property within the sequential sub-population structure is a plausible neural substrate for performing a repertoire of stable patterns during synchronized activity.

Development of network structure and synchronized firing patterns in dissociated culture of neurons

“…Dissociated culture of the cerebral cortex of rats was prepared on a high‐density CMOS microelectrode array (MEA). The culture protocol was based on a previous research with some modifications. Cerebral cortex was obtained from embryonic day 18 Wister rats and dissociated enzymatically in trypsin and physically by trituration.…”

“…In dissociated cultures of cerebral cortex of rodents, random Poisson‐like firings occur at early culture stages when neuronal network have not matured yet. As they mature, neuronal avalanche consists of diverse scale synchronized firings starts to appear . Synchronized firing patterns included within a neuronal avalanche changes from uniform to diverse as the culture matures .…”

“…As they mature, neuronal avalanche consists of diverse scale synchronized firings starts to appear . Synchronized firing patterns included within a neuronal avalanche changes from uniform to diverse as the culture matures . Functional structure changes in neuronal network might underlie this change.…”

“…Thus, in the present study, we measured collective synchronized firing patterns in dissociated cultures of the cerebral cortex of rats using a high‐density CMOS microelectrode array (MEA), and analyzed (i) what network structures correlates with repeatability, diversity and hierarchy of synchronized firing patterns, and (ii) how repeatability, diversity, and hierarchy of synchronized firing patterns and network structure change as neuronal networks develop.…”

Neurobiological mechanisms of state-dependent learning

“…Recent work is exploring the idea that spatiotemporal patterns of synchronized spontaneous activity in neuronal networks serve as memories [71], and it has recently been suggested that state-dependency accounts for the variety of such patterns [72**]. From an evolutionary perspective, SDL has also been conceptualized as a way to organize memories so that they can influence decision-making only under constrained conditions when access to specific information is particularly advantageous [5].…”