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Scientists Identify Central Neural Circuit for Itch Gating

Dec 06, 2019

Itch is a unique sensory experience, different from the sensation of pain, temperature and touch. Itch evokes a desire to scratch in human and many other animals. However, for patients suffering from the chronic itch, uncontrollable scratching causes severe skin and tissue damage.

To design better therapeutic approaches for alleviating chronic itch, it is necessary to gain better insight into the mechanisms of itch processing. The gastrin releasing peptide receptor+ (GRPR+) neurons in the dorsal horn of spinal cord play an important role in itch processing, but it remains unknown how these neurons are modulated by local and long-range inhibitory circuits.

In a recent study published in PNAS, Dr. SUN Yangang’s Lab at the Center for Excellence in Brain Science and Intelligence Technology, Institute of Neuroscience of the Chinese Academy of Sciences revealed the circuit mechanisms of inhibitory synaptic control of spinal GRPR+ neurons.

By combining the optogenetics with the patch-clamp recording method, Dr. SUN’s Lab found that spinal galanin+ inhibitory interneurons form inhibitory synapses with GRPR+ neurons in the spinal cord and play an important role in gating the GRPR+ neuron-dependent itch signaling pathway. 

Pharmacogenetic activation of spinal galanin+ neurons significantly suppressed the scratching behavior evoked by various pruritogens, but not the pain-related behaviors. Consistently, ablation of spinal galanin+ neurons significantly enhanced the scratching behavior evoked by various pruritogens. Furthermore, spinal GRPR+ neurons also receive strong inhibitory input from the rostral ventromedial medulla (RVM).

Thus, both local and long-range inhibitory neurons play important roles in gating the itch processing in the spinal cord by directly modulating the activity of spinal GRPR+ neurons.

This study revealed the mechanism underlying the inhibitory control of the spinal itch circuit, providing a basis for further dissection of the possible dysregulation of the itch circuit under pathological conditions leading to chronic itchiness.

Contact

SUN Yangang

Center for Excellence in Brain Science and Intelligence Technology

E-mail:

Synaptic control of spinal GRPR+ neurons by local and long-range inhibitory inputs

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