Abstract
Human brain is composed by 10 billion of neurons. The connection and signal flow between neurons form the functional unit-neural circuits. The rhythmic activities from neurons, together with their surrounding cells, glia, govern specific behaviors. Thus, the best way to understand how brain functions and modulated, is to zoom into the single neuron’s excitation, to see how their activities are established, maintained, and modulated elegantly. Understanding the molecular components of synaptic proteins, like N-methyl-D-aspartate (NMDA) receptors\K+ channels etc. and how neurons respond the environment like tissue stiffness and virus will provide critical mechanism of neuronal excitation origin. Moreover, developing novel techniques for the probe and manipulation of neuron or neural circuit, should significantly contribute to and promote the neuroscience field.
The special session includes five papers contributed by experts who have been studying neuronal excitation from different dimensions.
Zhou and his colleague [1] focused on how the excitatory-inhibitory (E/I) balance is maintain from the synaptic components view. They highlighted the critical role of NMDA receptors (NMDARs) in the establishment and maintenance of the E/I balance. This review also provided a briefly introduction of NMDARs, AMPARs and GABAARs, summarized the current studies on E/I balance mediated by NMDARs, and discussed the current advances in NMDAR-mediated AMPAR and GABAAR development. This paper may provide new therapeutic strategies for the recovery of E/I imbalance in neurological disorders.
In the brain, it is not just neurons. Neuronal excitation is also essentially modulated by a kind of no-excitatory cells, glial cells. One of them, named microglia, are the immune cells residing in the brain. They are involved in the maintenance of resting membrane potential, chemotaxis, phagocytosis of neurons by a variety of ion channels including large-conductance, calcium-activated and voltage-dependent potassium (BK) channel. Studies have demonstrated that BK channels modulate the activation, phagocytosis, and probably migration of microglia and have associated microglial BK channels with many neurological diseases, including neuropathic pain and stroke. Dr. Sun [2] summarizes the available information regarding the biophysical, functional, and pathological aspects of microglial BK channels and discusses future directions of research into these channels.
Moreover, neuronal excitation is also modulated by the neuronal environment, like substrate stiffness. Substrate stiffness is a microenvironment with certain rigidity structured by extracellular matrix, adjacent cells, etc. Substrate stiffness is a guidance cue for various biological processes besides chemical signals. However, it is unclear what the role of substrate stiffness is and exactly how it functions. Si et al. [3] review the effects of substrate stiffness on most nerve cell morphology and function in the central and peripheral nervous systems and their role in pathology. This review will be helpful for researchers interested in studying the role of substrate stiffness on nerve cells.
Another environment factor is the virus around us. In this issue, Zhang and Jiu [4] provide us one of the mechanisms of how virus COVID-19 affects our neuronal excitation. Except for the respiratory discomfort, numbers of COVID-19 patients showed clinic neurological symptoms such as headache, myalgia, loss of smell. Studies found that the cytoskeleton of nerve cells changed drastically in this process, indicating that cytoskeleton and its related proteins are closely related to the pathogenesis of nervous system diseases. In this review, they present the up-to-date association between host cytoskeleton and coronavirus infection in the context of the nervous system, and systematically summarize cytoskeleton-related pathogen-host interactions in both the peripheral and central nervous systems.
Lastly, we also invited Prof. Zhang to provide us a strong interdisciplinary technology: Activatable molecular fluorescence probes for the imaging and detection of ischemic stroke. Currently, various fluorescence probes have been synthesized with the aim of improving quantitative and quantitative studies of the pathologic processes of ischemic stroke in living animals. In this issue, Wang and Zhang [5] present an overview of current activatable fluorescence probes for the imaging and diagnosis of ischemic stroke in animal models. They categorize the probes based on their activatable signals for the biomarkers associated with ischemic stroke, and present detailed representative examples of their functional mechanisms.
In summary, this special issue covers a collection of studies from synaptic E/I balance, microglia BK channel, to neuronal response to substrate stiffness and COVID-19 virus. Advanced activatable molecular fluorescence probes also enable us to explore the underlying principles of brain functions and ischemic stroke, therefore holding great potential for the early diagnosis of brain disorders.
We hope our readers have learnt something from this special issue, and we would also like to thank all the authors for their valuable contributions to this special issue.