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| Poster #222 Behavioral effects of chemogenetically silencing mouse peripheral taste processing |
| Kathleen Depina1, Steven St. John2, Nirupa Chaudhari1,3 1Department of Physiology & Biophysics, University of Miami Miller School of Medicine, Miami, FL, United States 2Department of Psychology, Rollins College, Winter Park, FL, United States 3Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, United States |
Chemogenetic silencing uses inhibitory Designer Receptor Exclusively Activated by Designer Drugs (DREADD) to target neurons within a pathway. While many central sensory pathways have been explored using this tool, it has not been applied to peripheral taste processing. Initially, we validated the approach by expressing inhibitory DREADD in all peripheral sensory neurons (Pirt;hM4Di). After confirming expression, we injected a DREADD agonist, clozapine-N-oxide (CNO), intraperitoneally at 0.1-5mg/kg into Pirt;hM4Di mice. As expected, inhibition of proprioceptors severely reduced muscle tone and blocked motor function, confirming silencing. Next, we tested a transcriptionally and functionally distinct subset of gustatory neurons which express proenkephalin (Penk) and respond to sour, bitter, and high-salt stimuli. We measured lick rates of water-deprived Penk;hM4Di mice to preferred (water, 100mM sucrose) and avoided solutions (20mM citric acid [CA], 0.1mM quinine [Q], 890mM NaCl) following injection of either saline or 0.5-5mg/kg CNO. As expected, CA, Q and NaCl were strongly avoided in the control but also in the presence of CNO. Further, Penk;hM4Di mice increased overall drinking with CNO. To assess the basis for this increased consumption, we recorded ad lib water drinking of Penk;hM4Di mice to analyze licking microstructure. Compared to saline, CNO significantly increased water consumption, total licks, and burst duration and size; these effects were not observed in control mice. Possibly, in Penk;hM4Di mice, CNO acts on neurons in the hypothalamus to increase thirst or mechanosensors in the stomach to decrease feedback, thereby masking gustatory inhibition. We are continuing these studies with other strains of mice to assess the behavioral effect of chemogenetically silencing gustatory neurons. |