Mechanisms of mechanosensory transduction in Merkel cells

点击翻译按钮获取中文摘要

 DESCRIPTION (provided by applicant): The sense of touch is vital for our survival, as it is essential for purposes as simple as picking up a fork and as complex as bonding with a newborn. Despite its importance for accomplishing basic tasks, the molecular and cellular mechanisms that convert a force on the skin into a neural signal are poorly understood. The long term goal of this research is to elucidate how receptors in the skin convert a touch stimulus into a neural signal to inform our brains about the physical world. We use Merkel cell-neurite complexes, which are conserved discriminative touch receptors, as a model to study these processes. Merkel cells are epithelial derived target cells that contact the endings of sensory neurons that send information to the central nervous system. Stimulating these Merkel cell-neurite complexes generates slowly adapting type I responses, which are important for detecting object features such as edges and curvature. Our previous studies revealed that Merkel cells directly sense mechanical force and convey this information to the underlying sensory neurons. The molecules that govern this process are completely unknown. Numerous molecules involved in synaptic transmission and neurotransmitters have been identified in Merkel cells, yet attempts to identify signaling mechanisms in vivo have yielded contradictory results. Thus, the objective of this research is to identify mechanisms by which Merkel cells convey tactile information to the nervous system. We will accomplish this goal by using an innovative combination of transgenic mice, optogenetics, in vitro and ex vivo physiology, and behavioral studies. Our central hypothesis is that Merkel cells release neurotransmitters at TeNT-sensitive SNARE-dependent chemical synapses to excite firing in tactile afferents. In Aim 1, we will determine whether Merkel cells employ TeNT-sensitive SNARE-mediated vesicular release. Aim 2 will identify the neurotransmitter or neuromodulatory pathways that excite Merkel-cell afferent neurons. These studies will yield fundamental insights into peripheral tactile mechanisms, which is essential to advance basic knowledge of principles that govern encoding of somatic senses.