Summary: Academics have mapped over 70, 000 neural connections in mouse cells using a silicon chip with 4, 096 microhole wires, considerably advancing cerebral recording engineering. Unlike traditional particle imaging, which merely visualizes synapses, this approach also measures link strength, providing deeper understanding into mind network function.
The chip enables extremely sensitive cellular tapes from thousands of neurons at once by mimicking patch-clamp electrodes but on a large scale. This new style reveals extensive characteristics of each website, revealing 200 times more neural connections than their previous nanoneedle design.
The advancement of neurological tracking may transform how we study diseases and brain function. To better understand real-time neurological communication, researchers are now putting this system to use in life brains.
Major Information
- Massive Neural Mapping: The fresh golden device recorded 70, 000+ neural connections from ~2, 000 cells, far surpassing earlier techniques.
- Improved Recording Sensitivity: Microhole wires enabled 90 % successful intracellular tapes, vastly improving sign quality over earlier designs.
- Potential Life Head Software: Experts aim to adjust this technology for real-time neural activity modeling in survive animals.
Origin: Harvard
Using a golden device that can capture smaller but distinctive neural signals from a large number of cells, Harvard researchers mapped and catalogued more than 70, 000 neural connections from about 2, 000 mouse neurons.
The research, published in , Nature Biomedical Engineering,  , is a major advance in , neuronal recording and may help bring scientists a step closer to drawing a detailed synaptic connection map of the brain.
Higher-order brain functions are believed to be derived from the ways brain cells, or neurons, are connected.
Synapses are used to identify neuron-to-neuron contact points, and scientists are attempting to create synaptic connection maps that show which neurons connect to which other neurons and how strong each connection is.
Although electron microscopy has been successfully used to create visual maps of synaptic connections, these images lack information on connection strengths and, in turn, the neuronal network’s ultimate purpose.  ,  ,
In contrast, a , patch-clamp electrode, the gold standard in neuronal recording, can effectively get inside an individual neuron to record a faint synaptic signal with high sensitivity, and thus can find a synaptic connection and tell its strength.
Scientists have long tried to use high-sensitivity intracellular recording to record a sizable number of neurons simultaneously to measure and characterize a sizable number of synaptic signals and create a map annotated with connection strengths.
But they have rarely advanced past gaining instant intracellular access from a small number of neurons.
The  , researchers, led by , Donhee Ham, the John A. and Elizabeth S. Armstrong Professor of Engineering and Applied Sciences at the , Harvard John A. Paulson School of Engineering and Applied Sciences , ( SEAS ), developed an array of 4, 096 microhole electrodes on a silicon chip, which performed massively parallel intracellular recording of rat neurons cultured on the chip.
From these unprecedented recording data that abounded with synaptic signals, they extracted over 70, 000 synaptic connections from about 2, 000 neurons.
The work builds on the team’s 2020 , breakthrough , device – an array of 4, 096 vertical nanoneedle electrodes sticking out of a silicon chip of the same integrated circuit design.
A neuron could fit around a needle on this previous device to allow parallel intracellular recording, which was done using a lot of electrodes. The recording data still blows far past the patch-clamp limit of patch-clamp recording, which is ideal for removing about 300 synaptic connections from it.
The team was persuaded that the team could do better because the basic premise was in place. The design and fabrication of the silicon chip’s microhole electrode array, the electrophysiological recording, and the data analysis were led by co-lead authors Jun Wang and Woo-Bin Jung from the Ham group at SEAS.
In order to parallelize their intracellular recording, they used the chip to gently open up cells by applying small currents through the electrodes. Wang, a postdoctoral researcher, claimed the microhole design is comparable to the patch-clamp electrode, which is essentially a glass pipette with a hole at the end.
” Microhole electrodes are not only much more cost-effective than vertical nanoneedle electrodes, but they also are much simpler to make. They also better couple to the interiors of neurons. This ease of access is yet another crucial component of our work, Wang said.
The new design exceeded the team’s expectations. On average, more than 3, 600 microhole electrodes out of the total 4, 096 – that is, 90 percent – were intracellularly coupled to neurons on top.
70, 000 plausible synaptic connections were made when the team extracted these unprecedented network-wide intracellular recording data, compared to about 300 with their previous nanoneedle electrode array.
The recording data’s quality was also improved, enabling the team to categorize each synaptic connection based on its features and advantages.
According to Jung, a former postdoctoral researcher and current faculty member at Pohang University of Science and Technology in South Korea,” The integrated electronics in the silicon chip play as equally important a role as the microhole electrode, providing gentle currents in an elaborate way to obtain intracellular access.  ,
” One of the biggest challenges, after we succeeded in the massively parallel intracellular recording, was how to analyze the overwhelming amount of data”, Ham said. We have since come a long way in their understanding of synaptic connections. We are currently developing a more advanced design that can be used in a real brain.”
Paper co-authors include Rona S. Gertner of the Department of Chemistry and Chemical Biology, and Hongkun Park, the Mark Hyman, Jr. Professor of Physics and Professor of Chemistry.  ,
Funding: The research was supported by the , Samsung Advanced Institute of Technology , of Samsung Electronics.
About this news about neuroscience and AI research
Author: Anne Manning
Source: Harvard
Contact: Anne Manning – Harvard
Image: The image is credited to Neuroscience News
Original Research: Closed access.
Donhee Ham and colleagues ‘” Synaptic connectivity mapping among thousands of neurons via parallelized intracellular recording with a microhole electrode array” Nature Biomedical Engineering
Abstract
Using parallel intracellular recording and a microhole electrode array, synaptic connectivity mapping between thousands of neurons is performed.
The state of the art is limited to the mapping of about 300 synaptic connections, which makes it possible to measure synaptic signals across a neuronal network and thus the mapping and characterization of synaptic connections.
Here we report a 4, 096 platinum/platinum-black microhole electrode array fabricated on a complementary metal-oxide semiconductor chip for parallel intracellular recording and thus for synaptic-connectivity mapping.
The microhole–neuron interface, together with current-clamp electronics in the underlying semiconductor chip, allowed a 90 % average intracellular coupling rate in rat neuronal cultures, generating network-wide intracellular-recording data with abundant synaptic signals.
With an estimated overall error rate of about 5 %, we extracted more than 70, 000 plausible synaptic connections from more than 2, 000 neurons and classified them into electrical synaptic connections as well as into inhibitory, weak/uneventful, and strong/eventful excitatory chemical synaptic connections.
This scale of synaptic-connectivity mapping and the ability to characterize synaptic connections represent a step in the direction of large-scale neuronal network functional connectivity mapping.
