Criticality in neural cultures: Insights into memory and connectivity in entorhinal-hippocampal networks

The brain is a complex system of interconnected regions that underlie memory, cognition, and perception. Today, our understanding of the brain’s dynamic processes remains incomplete, particularly regarding differences in electrophysiological activity and inter-regional connectivity among specific areas. To explore this, we investigated the electrical activity, functional connectivity, and interactions of neural cultures differentiated into hippocampal, isocortical, and entorhinal networks using multi-electrode arrays (MEAs) to record extracellular local field potentials. Our results showed that collective synchronization events, or network bursts, were present in all cultures except for the hippocampal networks. Interestingly, introducing entorhinal neuron spheroids onto hippocampal cultures induced synchronized activity. Furthermore, Self-organized criticality analysis confirmed that all networks, except hippocampal cultures, were in a critical regime. Moreover, we found that entorhinal-hippocampal coupling facilitated criticality, promoting recurrent synchronized activity patterns. The consistent scaling exponents across configurations underscore the universality of criticality in biological networks. Finally, power spectrum analysis revealed a theta band peak in connected entorhinal-hippocampal cultures, consistent with in vivo studies, highlighting the role of theta oscillations in memory consolidation. Our findings provide more insights into brain functioning and offer an in vitro model for studying learning and memory.