Publication Date

2019-11-13

Availability

Embargoed

Embargo Period

2021-11-12

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PHD)

Department

Physiology and Biophysics (Medicine)

Date of Defense

2019-10-10

First Committee Member

Laura Bianchi

Second Committee Member

Gerhard Dahl

Third Committee Member

H. Peter Larsson

Fourth Committee Member

Kevin Collins

Fifth Committee Member

Lucia Carvelli

Abstract

The ability to sense touch is fundamentally important for interacting with and understanding the world around us. Touch plays a major role in many pathologies in which injury or inflammation leads to abnormal responses to touch, such as allodynia and mechanical hyperalgesia. Despite its crucial roles in physiology and pathology, the mechanisms by which we sense touch are the least understood of all the senses. Mammals sense touch through mechanosensors embedded in the skin, which are either free nerve endings or cooperative complexes formed by nerve endings and associated glia and epithelial cells. Work on Merkel cell-neurite complexes has demonstrated the necessity of the epithelial-derived Merkel cells for touch sensation. However, in mechanosensors that are formed by sensory nerve endings encapsulated by glia, such as the Pacinian and Meissner’s corpuscles, the role of the glia is less understood. In the nematode C. elegans, mechanoreceptors that sense touch to the nose are composed of nerve endings that are surrounded by glial sheath and socket cells, an arrangement similar to the mammalian corpuscle mechanosensors. It has previously been shown that the glia in C. elegans are necessary for proper function of the ensheathed sensory neurons, including mechanosensors. The Bianchi lab has published that DEG/ENaCs (Na+ channels) and K+ channels are needed in the glia surrounding sensory neurons for neuronal output and animal behavior (Wang et al., 2008, Wang et al., 2012, Han et al., 2013). Based on these findings, we proposed a model in which ensheathing glia of touch receptors excrete K+ in the microenvironment surrounding mechanosensitive neurons, thereby regulating their output via control of their excitability. Through the work described in this thesis, we have demonstrated that the activity of two specific glial Na+/K+-ATPase genes, EAT-6 and CATP-1, is also needed for touch in C. elegans. Furthermore, we have found that the requirement of these ATPases can be bypassed by a high glucose diet. The effect of glucose is dependent on ATP, translation, transcription, and the activity specifically in glia of CATP-2, a third Na+/K+-ATPase alpha subunit. Taken together, our results support metabolic and ionic cooperation between glia and neurons in C. elegans mechanosensors, a mechanism that might be conserved across species.

Keywords

C. elegans; Touch; Glia; Glia-Neuron Interaction; Sodium/Potassium ATPase

Available for download on Friday, November 12, 2021

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