Dynamic monitoring of inhibitory neural signals in brain tissue is a challenging task. Researchers have tried to track key substances involved in the neural inhibition process (e.g.,  Cl^-) in order to tackle this problem. However, Cl^- is a non-electrochemically active substance under physiological conditions and cannot easily undergo redox reactions based on electron transfer. As a result, Cl^- has not been a good candidate for use in monitoring inhibitory neural signals.

Now, however, researchers from the Institute of Process Engineering (IPE) of the Chinese Academy of Sciences have developed molecularly tailored liquid/liquid interfacial ultramicro iontronics (L/L UIs) for in vivo dynamic tracking of cerebral chloride (Cl^-) regulation.

This is the first time L/L UIs have been used to achieve highly sensitive, anti-interference, reversible, real-time dynamic tracking of non-electrochemically active Cl^- under physiological conditions. In this study, the L/L UIs were used for dynamic monitoring of Cl^- in the brains of an Alzheimer’s mouse model and epilepsy rat model.

The study was published in Science Advances on Dec. 4 (DOI: 10.1126/sciadv.adr7218).

“Unlike conventional electronics that use electrons as signal carriers, iontronics use ions as signal carriers, which represents a novel human-machine interface,” said Prof. BAI Shuo from IPE.

The L/L-UIs developed by the researchers consist of an ultra-micropipette with an organogel-filled tip, which forms a liquid/liquid interface with brain tissue after implantation. By modifying the liquid/liquid interface with a series of bis-thiourea ionophores (IPE_Cl-1, IPE_Cl-2, IPE_Cl-3) that recognize Cl^-, the researchers constructed ultramicro iontronics that can monitor Cl^- under physiological conditions. Under the action of these ionophores, Cl^- undergoes facilitated ion transfer reaction at the interface, thereby generating detectable electrical signals.

Figure 1. Schematic diagram of the design of L/L UIs and its dynamic tracing of Cl^- in the living brain of rodents (Image by LIANG Sen).

The researchers implanted the L/L UIs into specific brain regions (such as the hippocampus, striatum, and cortex) of Alzheimer’s model mice and epilepsy model rats. They then explored the differences in Cl^- concentrations between different brain regions. The L/L UIs showed high sensitivity, excellent anti-interference, and repeatability in real-time dynamic tracking of Cl^- in the living brains of the rodents.

Through this dynamic tracking of live rodent brains, the L/L UIs demonstrated the regulatory role of potassium-chloride cotransporter 2 (KCC2)—which plays an important role in the neuroinhibitory process—on the concentration of Cl^- in the brain.

This work is highly relevant to the field of neuroscience and has potential diagnostic and therapeutic implications for neurodegenerative diseases such as Alzheimer’s disease and epilepsy, according to a peer reviewer for Science Advances. “[It] provides new ideas for tracking non-electrochemically active ions and monitoring inhibitory neural signaling in brain tissue,” said the peer reviewer.

Media Contact:
LI Xiangyu
Public Information Officer
Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, P. R. China.
E-mail: xiangyuli@ipe.ac.cn 
Tel: 86-10-82544826