Harvard Team Maps 70,000 Neuronal Connections Using Innovative Silicon Chip Technology

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Breakthrough in Neuronal Mapping

Researchers at Harvard University have made a groundbreaking discovery by mapping over 70,000 synaptic connections among nearly 2,000 neurons in rats.

Using a cutting-edge silicon chip, the team was able to capture subtle synaptic signals from multiple neurons simultaneously.

Their findings, featured in Nature Biomedical Engineering, mark a significant leap forward in our understanding of how neuronal connections work, inching scientists closer to the ultimate goal of charting all synaptic connections in the brain.

Advancements Over Traditional Techniques

The relationships between neurons, known as synapses, are crucial for complex brain functions.

Neuroscience has long aimed to clarify not just which neurons form connections, but also the strength of these connections, as this is essential for grasping the operational dynamics of neural networks.

Although traditional electron microscopy has effectively visualized synaptic connections, it has limitations.

This method falls short when it comes to assessing connection strength, an element vital for understanding overall network functionality.

The patch-clamp technique, widely recognized as the gold standard for neuronal recording, permits sensitive measurements from individual neurons.

This approach helps researchers identify synaptic connections and evaluate their strength.

However, extending this high-sensitivity recording capability to larger groups of neurons simultaneously has posed significant challenges.

Innovative Engineering Behind the Research

Leading the charge on this innovative research is Donhee Ham, a professor at Harvard’s John A. Paulson School of Engineering and Applied Sciences.

Ham and his team engineered a silicon chip equipped with an impressive array of 4,096 microhole electrodes.

This novel design allowed for massively parallel intracellular recordings from cultured rat neurons positioned on the chip.

The outcome was an abundance of synaptic signals, revealing more than 70,000 synaptic connections.

This recent development builds upon the team’s earlier work, which featured a different device incorporating vertical nanoneedle electrodes on a silicon chip.

While that earlier design successfully uncovered around 300 synaptic connections, the new microhole electrode layout dramatically improved data collection capabilities.

Co-lead researchers Jun Wang and Woo-Bin Jung were instrumental in the design and fabrication of the microhole array.

They also handled the recordings and data analysis.

Their methodology included precision techniques that gently introduced small currents, facilitating access to the interiors of the neurons.

Wang emphasized the advantages of the microhole electrodes, pointing out that they create a significantly stronger connection to neurons than the previous nanoneedle design.

He also noted that the new design is easier to fabricate, enhancing its real-world applicability.

Remarkably, nearly 90% of the 4,096 electrodes formed successful connections with neurons, drastically increasing the identified synaptic connections.

This method not only expanded the scope of observations but also improved the quality of recorded data, enabling a thorough categorization of each synaptic connection based on its characteristics and strength.

Jung highlighted the pivotal role of integrated electronics within the silicon chip, which can deliver precise electrical currents required for intracellular access while simultaneously capturing neuronal signals.

Ham acknowledged the achievement of successful parallel intracellular recordings but noted that analyzing the vast amounts of data generated is the next significant challenge.

The research team is now setting its sights on developing designs suitable for investigations in live brain settings.

Alongside Ham, contributing authors include Rona S. Gertner from the Department of Chemistry and Chemical Biology and Hongkun Park, who is the Mark Hyman, Jr. Professor of Chemistry and a Professor of Physics.

This research was generously funded by the Samsung Advanced Institute of Technology, part of Samsung Electronics, highlighting the intersection of academia and industry in advancing our understanding of the brain.

Their support has enabled significant progress in developing novel materials and technologies that mimic neural processes.

This collaboration has not only deepened our knowledge of brain-inspired systems but also contributed to a breakthrough in organic electronics, paving the way for more efficient and flexible bioelectronic devices.

Such advancements underscore the potential of industry-academia partnerships in driving cutting-edge innovations.

Source: ScienceDaily