An Anterior Cingulate Cortex-to-Midbrain Projection Controls Chronic Itch in Mice / 神经科学通报·英文版

Itch is an unpleasant sensation that provokes the desire to scratch. While acute itch serves as a protective system to warn the body of external irritating agents, chronic itch is a debilitating but poorly-treated clinical disease leading to repetitive scratching and skin lesions. However, the neural mechanisms underlying the pathophysiology of chronic itch remain mysterious. Here, we identified a cell type-dependent role of the anterior cingulate cortex (ACC) in controlling chronic itch-related excessive scratching behaviors in mice. Moreover, we delineated a neural circuit originating from excitatory neurons of the ACC to the ventral tegmental area (VTA) that was critically involved in chronic itch. Furthermore, we demonstrate that the ACC→VTA circuit also selectively modulated histaminergic acute itch. Finally, the ACC neurons were shown to predominantly innervate the non-dopaminergic neurons of the VTA. Taken together, our findings uncover a cortex-midbrain circuit for chronic itch-evoked scratching behaviors and shed novel insights on therapeutic intervention.

Postsynaptic Targeting and Mobility of Membrane Surface-Localized hASIC1a / 神经科学通报·英文版

Acid-sensing ion channels (ASICs), the main H

Cell-Type Identification in the Autonomic Nervous System / 神经科学通报·英文版

The autonomic nervous system controls various internal organs and executes crucial functions through sophisticated neural connectivity and circuits. Its dysfunction causes an imbalance of homeostasis and numerous human disorders. In the past decades, great efforts have been made to study the structure and functions of this system, but so far, our understanding of the classification of autonomic neuronal subpopulations remains limited and a precise map of their connectivity has not been achieved. One of the major challenges that hinder rapid progress in these areas is the complexity and heterogeneity of autonomic neurons. To facilitate the identification of neuronal subgroups in the autonomic nervous system, here we review the well-established and cutting-edge technologies that are frequently used in peripheral neuronal tracing and profiling, and discuss their operating mechanisms, advantages, and targeted applications.

Acid-sensing ion channels as a target for neuroprotection: acidotoxicity revisited / 生理学报

Protons are widespread in cells and serve a variety of important functions. In certain pathological conditions, acid-base balance was disrupted and therefore excessive protons were generated and accumulated, which is termed acidosis and proved toxic to the organism. In the nervous system, it has been reported that acidosis was a common phenomenon and contributed to neuronal injury in various kinds of neurological diseases, such as ischemic stroke, multiple sclerosis and Huntington's disease. Acid-sensing ion channels (ASICs) is the key receptor of protons and mediates acidosis-induced neuronal injury, but the underlying mechanism remains unclear. Traditionally, Ca(2+) influx through homomeric ASIC1a channels has been considered to be the main cause of acidotoxicity. Recent research showed that extracellular protons trigger a novel form of necroptosis in neurons via ASIC1a-mediated serine/threonine kinase receptor interaction protein 1 (RIP1) activation, independent of ion-conducting function of ASIC1a. In addition, ASIC1a was found in mitochondria and regulated mitochondrial permeability transition-dependent neuronal death. In this article, we will review the recent progresses on the mechanisms underlying ASIC-mediated neuronal death and discuss ASIC modulators involved in this process.

Properties of whole-cell potassium currents in mechanically dissociated Drosophila larval central neurons / 生理学报

By electrophysiological methods, cultured Drosophila embryonic and larval central neurons have been widely used to study ion channels, neurotransmitter release and intracellular message regulation. Voltage-activated K(+) channels play a crucial role in repolarizing the membrane following action potentials, stabilizing membrane potentials and shaping firing patterns of cells. In this study, a mechanical vibration-isolation system was used to produce a sufficient number of acutely dissociated larval central neurons, of which the majority were type II neurons (2~5 microm in diameter). Using patch clamp technique, the whole-cell K(+) currents in type II neurons were characterized by containing a transient 4-AP-sensitive current (I(A)) and a more slowly inactivating, TEA-sensitive component (I(K)). According to their kinetic properties, five types of whole-cell K(+) currents were identified. Type A current exhibited primarily fast transient K(+) currents that activated and inactivated rapidly. The majority of the neurons, however, slowly inactivated K(+) currents with variable inactivation time course (type B current). Type C current, being present in a small number of the cells, was mainly composed of noninactivating components. Some of the neurons expressed both transient and slow inactivating components, but the slowly inactivating components could reach more than 50% of the peak current (type D current). Type E current showed distinct voltage-dependent activation properties, characterized by its bell-shaped activation curve. Type E current was inhibited by application of Ca(2+)-free solution or 0.1 mmol/L Cd(2+). Moreover, this novel current ran down much more rapidly than other types. These results indicate that different K(+) channels, which have different kinetic and pharmacological properties, underlie the whole-cell K(+) currents in type II neurons of Drosophila larval central nervous system.