Optogenetic activation of mechanically insensitive afferents in mouse colorectum reveals chemosensitivity
| Autor: | Bin Feng, Sonali Joyce, Gerald F. Gebhart |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Rhodopsin Light Signal Transduction endocrine system diseases Colon Physiology Single fiber Neurogastroenterology and Motility Sensory system Optogenetics Mechanotransduction Cellular Bile Acids and Salts Mice 03 medical and health sciences Osmotic Pressure Physiology (medical) medicine Animals Neurons Afferent Irritable bowel syndrome Hepatology biology business.industry Rectum Gastroenterology Anatomy medicine.disease digestive system diseases Mice Inbred C57BL 030104 developmental biology biology.protein Female business Neuroscience |
| Zdroj: | American Journal of Physiology-Gastrointestinal and Liver Physiology. 310:G790-G798 |
| ISSN: | 1522-1547 0193-1857 |
| DOI: | 10.1152/ajpgi.00430.2015 |
| Popis: | The sensory innervation of the distal colorectum includes mechanically insensitive afferents (MIAs; ∼25%), which acquire mechanosensitivity in persistent visceral hypersensitivity and thus generate de novo input to the central nervous system. We utilized an optogenetic approach to bypass the process of transduction (generator potential) and focus on transformation (spike initiation) at colorectal MIA sensory terminals, which is otherwise not possible in typical functional studies. From channelrhodopsin2-expressing mice (driven by Advillin-Cre), the distal colorectum with attached pelvic nerve was harvested for ex vivo single-fiber recordings. Afferent receptive fields (RFs) were identified by electrical stimulation and tested for response to mechanical stimuli (probing, stroking, and stretch), and afferents were classified as either MIAs or mechanosensitive afferents (MSAs). All MIA and MSA RFs were subsequently stimulated optically and MIAs were also tested for activation/sensitization with inflammatory soup (IS), acidic hypertonic solution (AHS), and/or bile salts (BS). Responses to pulsed optical stimuli (1–10 Hz) were comparable between MSAs and MIAs whereas 43% of MIAs compared with 86% of MSAs responded tonically to stepped optical stimuli. Tonic-spiking MIAs responded preferentially to AHS (an osmotic stimulus) whereas non-tonic-spiking MIAs responded to IS (an inflammatory stimulus). A significant proportion of MIAs were also sensitized by BS. These results reveal transformation as a critical factor underlying the differences between MIAs (osmosensors vs. inflammatory sensors), revealing a previously unappreciated heterogeneity of MIA endings. The current study draws attention to the sensory encoding of MIA nerve endings that likely contribute to afferent sensitization and thus have important roles in visceral pain. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|