LATEST UPDATES » Vol 25, No. 02, February 2022 – A Step into The Future: Innovative Ideas to Shape the Technology of Tomorrow       » New Bio-inspired Material Could Replace Conventional Plastics       » Partnership for Development of AI-Powered Telehealth-Radiology Platform       » Delivering a Complete Digital Health Ecosystem through Strategic Partnership       » Motivational Robots to Help Improve Learning       » Hope for Vaccine Against Herpes Virus      
Vol 25, No. 02, February 2021   |   Issue PDF view/purchase
Understanding the Molecular Mechanism Behind Information Processing in the Brain
Team of researchers from University of Science and Technology of China (USTC) and Shenzhen Institutes of Advanced Technology (SIAT) of the Chinese Academy of Sciences (CAS) observe individual GABAA receptors and their organization on the synaptic membrane, explaining the brain's ability for information processing.

Synapses are gaps between neurons that allow the cellular transmission of signals from one neuron to the next. The efficient transmission of synaptic signals relies on the delicate structure and complex molecular composition of the synapses. However, the small size and heterogeneous nature of the synapses pose significant challenges in direct observation of the molecules inside synapses.

Based on the proposed processing technique for in situ cryo-electron tomography, researchers from University of Science and Technology of China (USTC) and Shenzhen Institutes of Advanced Technology (SIAT) of the Chinese Academy of Sciences (CAS) became the first scientists to observe individual GABAA receptors and their organization on the synaptic membrane, to understand the molecular building blocks of brain information processing.

“The advance of this study comes from the in situ cryo-electron microscopy, a method that preserves the cells in native states and has an order of magnitude of higher resolution compare to the super-resolution optical microscopy,” said Tao Changlu, postdoctoral fellow from USTC and the study's co-first author, now associate investigator at SIAT.

This image processing technique is able to automatically locate the membrane proteins in their cellular context. “To ensure that we detect every receptor on the postsynaptic membrane, we oversampled the synaptic membrane and classified all the sampled 3D images without any template,” said Liu Yuntao, graduate student from USTC and the study's co-first author, now postdoctoral fellow at UCLA. “We even used the negative control that sampling the presynaptic membrane to validate our observation.”

Once the receptors were detected, researchers noticed that the receptors are not randomly distributed on the membrane: they tend to keep the same 11 nanometres from each other. Intriguingly, the receptors were able to rotate freely, even though constrained by distance.

“The distancing among receptors could arise from their interactions with scaffolding molecule—gephyrins,” said Bi Guoqiang, Professor of neuroscience at USTC and senior author of the paper.

The scaffolding molecules form a five-nanometre thick density sheet to support and regulate GABAA receptors on the membrane. Together, they form an absorbing semi-ordered structure called "mesophasic assembly".

A mesophasic state is in between the liquid and solid, which might be induced by the multivalent interaction between receptors and their scaffolding molecules and attract the readily-releasable vesicles containing neurotransmitters. The inhibitory synapses could store information by arranging the GABAA receptors in such a low-entropy Goldilocks state.

This semi-ordered structure differs from the previously proposed hexagonal lattice organization of GABAA receptors and gephyrins. Notably, each synapse tends to contain one mesophasic assembly, rather than multiple nano-domains as observed in excitatory synapses with super-resolution optical microscopy.

“This work represents the first nanometer-resolution observation at the inhibitory synaptic receptors and a critical step towards resolving the atomic details of the brain.” Said Zhou Hong, Director of the Electron Imaging Center for NanoMachines at the California NanoSystems Institute at UCLA, also senior author of the paper.

news CPhI & P-MEC China gives a glimpse of the success returning pharma events will deliver in 2021
news Highlights from the E&L China 2020 Conference
news Asia’s ageing population drives development of rehabilitation technologies targeting elderly disabilities
news Virtual Expo Connect to empower access for international pharma to the world’s largest pharma ingredients market

About Us
Available issues
Editorial Board
Letters to Editor
Contribute to APBN
Advertise with Us
World Scientific Publishing Co. Pte. Ltd.
5 Toh Tuck Link, Singapore 596224
Tel: 65-6466-5775
Fax: 65-6467-7667
» For Editorial Enquiries:
   biotech_edit@wspc.com or Ms Deborah Seah
» For Subscriptions, Advertisements &
   Media Partnerships Enquiries:
Copyright© 2021 World Scientific Publishing Co Pte Ltd  •  Privacy Policy