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.

“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.

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

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.