Unlike electronic circuits in computers that use electrical signals alone to process information, cells in the brain use a collection of interacting biological signals to achieve brain function. These biological signals include ion concentrations, molecular messenger levels, protein activities, and other biophysical dynamics. They form signal transduction networks in single cells and collectively convert cellular inputs into cellular outputs by interacting in complex ways. These interactions result in complex and coordinated dynamics of the biological signals, and disruption of this harmony leads to symptoms of neurological disorders such as deficits in cognition, learning, and memory. Just as it is difficult to fully appreciate a symphony by only listening to one or two instruments in the orchestra, understanding the complex biological dynamics and neural computations in the brain requires observations of many biological signals simultaneously.
Genetically encoded fluorescent reporters for many of the biological signals have been developed, which have transformed biology and neuroscience research by enabling direct and quantitative measurements of biological signals under optical microscopes. However, no more than a couple of biological signals can be measured at the same time via fluorescent reporters because the light signals from different reporters can only be distinguished by their distinct fluorescence spectra (or ‘colors’), of which there are few.
To overcome the color limitation on multiplexed signaling readout, Linghu explored whether ‘space’ can be used as a new dimension to multiplex the simultaneous time course measurements of biological signals. He has developed a new way of imaging that enables simultaneous recording of many biological signals in the brain, using the spatial dimension as a resource. By simultaneously observing five different biological signals, namely Ca2+, cAMP, PKA, protein kinase C (PKC), and extracellular signal-regulated kinase (ERK) activities in neurons, he studied the dynamical principles of signaling activities during neural plasticity.
By enabling observations of the symphony of neural activity, this new technology will pave the way for fundamental understandings of multi-dimensional dynamics underlying brain function and open up new ways to pinpoint the exact differences of the biological dynamics between health and disease. The dynamical principles of neural computation revealed by such multiplexed signaling readout will also provide insights into future developments of neural-inspired artificial systems.
