Summary: Researchers are using silicon chips with 4,096 microhole electrodes to map over 70,000 synaptic connections of rat neurons, and are significantly advancing neuronal recording technology. Unlike traditional electron microscopes that visualize only synapses, this method also measures connection strength and provides deeper insight into brain network function.
The chip mimics patch clamp electrodes, but allows for very sensitive intracellular recordings from thousands of neurons at large scale. Compared to previous nanonedle designs, this new approach captured 200 times the synaptic connections and revealed detailed properties of each link.
This technology could revolutionize neural mapping and provide a powerful tool to study brain function and disease. Researchers are currently working to apply the system to live brains to further understand real-time neural communication.
Important facts
Large scale neural mapping: The new silicon chip records over 70,000 synaptic connections from ~2,000 neurons, far exceeding previous methods. Improved Recording Sensitivity: Enabling microhole electrodes, 90% successful, significantly improving signal quality in previous designs. Aim to adapt this technique to real-time neural activity mapping in living animals.
Source: Harvard
Harvard researchers have mapped and cataloged over 70,000 synaptic connections from around 2,000 rat neurons, using silicon chips that can record small but-taltered synaptic signals from a large number of neurons.
The study published in Nature Biomedical Engineering is a major advance in neuronal recordings and may help scientists take a step closer to drawing detailed synaptic connection maps in the brain.
Higher brain functions are thought to stem from the way brain cells or neurons are connected.
The interneuronal contact points are called synapses, and scientists try to draw a synaptic connection map that shows not only which neurons connect to other neurons, but how strong each connection is.
Electron microscopy has been used with great success to create visual maps of synaptic connections, but these images do not have information on the connection strength and therefore the final function of the neuronal network.
In contrast, patch clamp electrodes, the gold standard for neuronal recording, effectively enter individual neurons, recording highly sensitive faint synaptic signals, finding synaptic connections and transmitting their strength. can.
Scientists have attempted to apply such sensitive intracellular records parallel to numerous neurons to measure and characterize numerous synaptic signals.
However, they were rarer than obtaining intracellular access from a handful of neurons at once.
Donhee Hamm, John A, and Elizabeth S. Armstrong Armstrong Engineering and Applied Science (Sea) researchers led by Elizabeth S. Armstrong Engineering and Applied Science (Sea) have 4,096 micros on silicon We have developed an arrangement of hole electrodes. Chip performed highly parallel intracellular recordings of rat neurons cultured in the chip.
From these unprecedented recorded data, which are rich in synaptic signals, we extracted over 70,000 synaptic connections from approximately 2,000 neurons.
This work is based on the team’s groundbreaking device of 2020. This is an array of 4,096 vertical nanoneddle electrodes protruding from the silicon chip of the same integrated circuit design.
In this previous device, neurons were able to wrap the needle and allow for intracellular recording. This was parallelized through a large number of electrodes. In the best case, approximately 300 synaptic connections can be extracted from recorded data.
With the basic premise in hand, the team doubted they could do better. CoLead author Jun Wang and Jung of Ham Group of Woo-bin Jung of Seas led the design and fabrication of microhole electrode arrays on silicon chips, electrophysiological recordings and data analysis.
They manipulated the chip to gently open the cells with small current injections through the electrodes to parallelize the intracellular recordings. The King of Postdoctoral Researchers said the microhole design resembles a patch clamp electrode. This is essentially a glass pipette with an electrode cover with holes at the ends.
“Microhole electrodes not only provide better binding to neuronal interiors than vertical nanoneddle electrodes, but are much easier to manufacture. This accessibility is another important feature of our work,” Wang said. says.
The new design exceeded the team’s expectations. On average, more than 3,600 microhole electrodes out of a total of 4,096, or 90%, were bound intracellularly to the upper neurons.
The number of synaptic connections extracted by the team from such unprecedented network-wide intracellular data bloomed at 70,000 plausible synaptic connections, compared to about 300 in previous nanotype electrode arrays.
The quality of recorded data was also excellent, allowing the team to classify each synaptic connection based on its characteristics and strengths.
“The integrated electronics in silicon chips play an important role just like microhole electrodes, providing gentle currents in an elaborate way to gain intracellular access while simultaneously recording intracellular signals.” He is currently a professor at Pohan University of Science and Technology in Korea.
“One of the biggest challenges was how to analyze an overwhelming amount of data after a successful intracellular recording in a very parallel manner,” Ham said. “Since then, we have come a long way to gain insight into synaptic connections from them. We are currently working towards new designs that can be deployed in the living brain.”
The paper co-authors include Rona S. Gertner, Faculty of Chemical Chemistry and Biology, and Mark Hyman, Jr. Includes Hongkun Park, professor of chemistry and physics.
Funding: This study was supported by the Samsung Advanced Institute of Samsung Electronics.
About this AI and Neuroscience Research News
Author: Anne Manning
Source: Harvard
Contact: Ammanning – Harvard
Image: Image credited to Neuroscience News
Original Research: Closed Access.
Donhee Ham et al. Natural Biomedical Engineering
Abstract
Synaptic connection mapping between thousands of neurons via parallelized intracellular recordings using microhole electrode arrays
Large-scale parallelization of neuronal intracellular recordings allows for measurement of synaptic signals across neuronal networks, thus enabling mapping and characterization of synaptic connections. connection.
Here we report a 4,096 platinum/platinum black microhole electrode array fabricated on complementary metal oxide semiconductor chips for parallel intracellular recordings and therefore synaptic connectivity mapping.
The microhole-neuron interface, along with current clamp electronics on the underlying semiconductor chip, allows for 90% average intracellular coupling rates in rat nerve cultures, providing intracellular recording data across the network with abundant synaptic signals. It’s generated.
From these data, we extract over 70,000 plausible synaptic connections between over 2,000 neurons and catalog them into electrical synaptic connections, inhibitory, weak/caliber/caliber excitatory/potential excitatory chemical synaptic connections It has been cataloged in. %.
This scale of synaptic connectivity mapping and the ability to characterize synaptic connections are steps towards functional connectivity mapping of large-scale neuronal networks.
