内耳由专司听觉的耳蜗和专司平衡功能(包括凝视稳定,姿势控制和空间导航)的前庭器官组成。这两个系统司职不同功能,但具有相同的发育起源,并且都依赖机械敏感性毛细胞。与其他感觉系统(例如视觉,躯体感觉系统等)相比,我们对内耳神经元的分子多样性及其对形态,生理和功能分化的影响所知甚少。博后期间我发现了听觉系统的初级神经元可分为三种有显著分子差异的亚型。这三种亚型表现出相应的形态与电生理特性。亚型的分化在出生后完成,并依赖听觉系统的感官活动,为听觉系统的研究提供了重要的理论基础与全新的视角。
前庭系统司职平衡觉。其功能失衡导致的平衡障碍影响成年人口的15%,尤其是老年人。而与听觉等其他感觉系统相比,我们对这神秘的“第六感”了解极其有限。前庭神经节神经元支配五个独特的终末器官,以实现姿势控制、空间导航和自主调节等各类功能。相应的,其形态与生理特性均有明显差异。我们将从前庭神经节神经元的分子多样性着手,利用单细胞测序、光遗传与化学遗传学、钙成像、行为分析等方法阐释前庭系统形态、生理与功能多样性形成的分子机制。
The inner ear consists of the cochlea,
dedicated to hearing and the vestibular organs, dedicated to balance functions,
including gaze stabilization, postural control and spatial navigation. These
two systems share the same developmental origin and mechanosensitive hair cells
are used by both but to achieve distinct functions. Comparing to other sensory
systems (e.g. visual, somatosensory), the molecular heterogeneity of neurons in
the inner ear and how they contribute to the morphological, physiological and
functional diversity have not been well-established and appreciated. I demonstrated,
during my postdoc, that type I SGNs consist of three molecularly distinct
subtypes (named type Ia, type Ib and type Ic), which exhibit anatomical and
physiological differences. Specification of the subtypes is finished
postnatally in an activity dependent manner. These results can provide new
angles for the mechanistic understanding of sensory coding in the auditory
system.
The vestibular system is critical to our sense of balance and spatial orientation.
Malfunctions of the system lead to balance disorders that can affect 15 percent
of the adult population, especially the elderly. Comparing to other sensory
systems, such as the auditory system, this second part of the inner ear has
drawn less public or scientific attention. Vestibular ganglion neurons (VGNs)
innervate five distinctive end organs to carry out diverse functions ranging
from gaze stabilization and spatial navigation to cognitive functions and
autonomic regulations. Accordingly, VGNs exhibit pronounced anatomical and
physiological diversity. We plan to begin the characterization of the
vestibular circuitries with the molecular and cellular diversity of the
vestibular ganglion neurons.
发表文章
1. Sun S, Siebald C, Mueller U. (2021) Subtype Maturation of Spiral Ganglion Neurons. Current Opinion in Otolaryngology &
Head and Neck Surgery 29(5):391-399.
2. Sun S*, Babola T*, Palermo A*, So K, Nguyen M, Su S,
Palermo A, Bergles D, Burns J, Mueller U. (2018) Hair Cell Mechanotransduction
Regulates Spontaneous Activity and Spiral Ganglion Subtype Specification in the
Auditory System. Cell 174(5):1246-1632. *contributed equally
to this work.
Highlighted/previewed in:
Whalley, Nature Review Neuroscience.
19,579 (2018)
Kandler, Neuron. 2018.07.043
Fekete, F1000.
3. Sun S*, Xu Q*, Guo C, Guan Y,
Liu Q and Dong X. (2017) Leaky gate model: intensity-dependent coding of pain
and itch in the spinal cord. Neuron, 93(4):840-853. *contributed equally
to this work.
Highlighted/previewed in:
Pereira and Lerner, Neuron. 2017.02.016
4. Sun S, Dong X. (2016) Trp channels and itch. Seminars in immunopathology 38(3), 293-307.
5. Reddy
VB*, Sun S*, Azimi E, Elmariah SB,
Dong X, Lerner EA. (2015) Redefining the concept of protease-activated
receptors: cathepsin S evokes itch via activation of Mrgprs. Nature communications, 6:7864. *contributed equally to this work.
6. Li Z, Tseng P.-Y, Tiwari
V, Xu Q, He S.-Q, Wang Y, Zheng Q, Han L, Wu Z, Blobaum A.L, Cui Y, Tiwari V, Sun
S, Cheng Y, Huang-Lionnet J.H.Y, Geng Y, Xiao B, Peng J, Hopkins C, Raja
S.N, Guan Y, Dong X. (2017) Targeting human Mas-related G protein-coupled
receptor X1 to inhibit persistent pain. Proc. Natl. Acad. Sci, 114(10): E1996-2005.
7. Kim YS, Chu Y, Han L, Li M, Li Z, Lavinka PC, Sun S, Tang Z, Park K, Caterina MJ, Ren
K, Dubner R, Wei F, Dong X. (2014) Central terminal sensitization of TRPV1 by
descending serotonergic facilitation modulates chronic pain. Neuron, 81(4):873-87.
8. Liu Q, Sikand P, Ma C, Tang Z, Han L, Li Z, Sun S, LaMotte RH, Dong X. (2012)
Mechanisms of itch evoked by β-alanine. J
Neurosci.3509-12.
Invited Book Chapters
Itch and Pain: Similarities,
Interactions and Differences
Chapter: Interneurons and Their Roles
in Itch and Pain, Author: Shuohao Sun
International Association for the Study
of Pain Press (2020年7月)