MINI REVIEW article
Front. Synaptic Neurosci.
From Microelectrode Arrays to All-Optical and Multimodal Neural Interfaces: Emerging Platforms for Spatiotemporal Interrogation of In Vitro Neural Circuits
Provisionally accepted
- 1The University of Melbourne, Parkville, Australia
- 2The Florey Institute of Neuroscience and Mental Health, Parkville, Australia
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Understanding how synaptic interactions lead to circuit dynamics for neural computation requires experimental tools that can both observe and perturb neuronal activity across spatial and temporal scales. Microelectrode arrays (MEAs) provide scalable access to population spiking activity, yet they lack the spatial resolution and molecular specificity to precisely dissect synaptic mechanisms. In contrast, recent advances in optogenetic actuators, genetically encoded calcium and voltage indicators, and patterned photostimulation have transformed in vitro research, enabling all-optical interrogation of synaptic plasticity, functional connectivity, and emergent network dynamics. Further progress in transparent MEAs and hybrid optical–electrical systems has bridged the divide between electrophysiology and optical control, allowing simultaneous, bidirectional interaction with biological neural networks (BNNs) and real-time feedback modulation of activity patterns. Together, these multimodal in vitro platforms provide unprecedented experimental access to how local interactions shape global network behavior. Beyond technical integration, they establish a foundation for studying biological computation, linking mechanistic understanding of synaptic processes with their computational outcomes. This mini-review summarizes the progression from conventional MEA-based electrophysiology, through all-optical interrogation, to integrated multimodal frameworks that unite the strengths of both modalities.
Keywords: microelectrode array, All-optical interrogation, Patterned photostimulation, multimodalneural interfaces, synaptic plasticity, network dynamics, neural computation
Received: 27 Oct 2025; Accepted: 27 Nov 2025.
Copyright: © 2025 Sun, Wang, Gordon, French and Unnithan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Dechuan Sun
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