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Worcester Polytechnic Institute Digital WPI Doctoral Dissertations (All Dissertations, All Years) Electronic Theses and Dissertations 2018-10-03 Decoding Neural Circuits Modulating Behavioral Responses to Aversive Social Cues Christopher Chute Worcester Polytechnic Institute, [email protected] Follow this and additional works at: https://digitalcommons.wpi.edu/etd-dissertations Repository Citation Chute, C. (2018). Decoding Neural Circuits Modulating Behavioral Responses to Aversive Social Cues. Retrieved from https://digitalcommons.wpi.edu/etd-dissertations/496 This dissertation is brought to you for free and open access by Digital WPI. It has been accepted for inclusion in Doctoral Dissertations (All Dissertations, All Years) by an authorized administrator of Digital WPI. For more information, please contact [email protected]. DECODING NEURAL CIRCUITS MODULATING BEHAVIORAL RESPONSES TO AVERSIVE SOCIAL CUES A Dissertation Submitted to the Faculty of Worcester Polytechnic Institute In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biology and Biotechnology October 2018 1 Preface Octopamine succinylated #9, osas#9, was discovered and published in June of 2013. Less than two months later I joined the lab and took “osas#9” under my wing. When I started there was three things known about osas#9: 1) The small ascaroside is produced by starved larval stage 1 (L1) animals, 2) starved C. elegans respond aversively to the compound, and 3) starved animals subjected to the compound plus E. coli, no longer avoid osas#9. Now, five years later, we have developed an extensive model for the underlying circuitry driving response and modulation to osas#9. Of course, I say we because it was a group effort, involving discussion with peers, input from collaborators, and assistance from undergraduates. And, of course, guidance by the principal investigator, Jagan Srinivasan. A special thanks is warranted to all of the JS lab members, present and past, who helped achieve the goals of this dissertation. But it was not just the compound that was new, Jagan was a new faculty member, our lab manager was straight out of undergraduate school, and I was a first generation college student starting graduate school. To say the least, it was an adventure. In particular, it would be impossible not to individually mention Laura Innarelli (Aurillio), whom I began my PhD journey with. She started as Jagan’s lab manager just weeks before I arrived (and sadly left before my final year). Throughout four years she was pivotal in keeping the lab running smoothly, from ordering essentials to prepping daily media. She went above and beyond that with discussions and edits, and more importantly, friendship. After one year, Doug Reilly joined the lab, who along with Laura offered many laughs and… distractions. But daily crosswords and memes made for a great and productive environment. I especially would like to thank Doug for taking the 2 time to read through this dissertation and offer edits and comments. This last year, Liz DiLoreto took over as lab manager and kept things running like a well-oiled machine. All of the members, from volunteers to graduate students, made for a fun environment over the years. With Jagan operating a new lab, no senior lab members, and three lab locations (two relocations over the course of my time here), it was quite the memorable experience. This meant many trial and error scenarios over the years, from molecular cloning techniques to setting up new equipment and developing new assays for the lab. One thing that was constant though, “The Fix”, which is a burger bar responsible for keeping us all satiated (maybe a bit too much) and bonding outside of lab to fulfill Jagan’s desire to have a lab that felt more like a group of friends with a common goal rather than a workplace. After a few months of performing avoidance assays with a mouth pipette (I know) I was becoming quite concerned with how the next few years would pan out. Little did I know just how quickly, and simultaneously, I would be exposed to a plethora of techniques and investigative strategies making for a fulfilled graduate career. One thing I did not anticipate learning, especially so quickly, was communication with leading PI’s from the field. Of course, if you know Jagan, this is his strategy: jump in, get the experience, and learn. He connected me to many PIs, led to two important collaborations resulting in authorships, and most importantly - taught me to be confident in disseminating my knowledge to superiors and peers in person or via email. I will never forget the first oral presentation at a local worm meeting (just 9 months in), where he said before-hand “don’t worry, there will be a Nobel Laureate in the audience”. But this sort of urging and pressure 3 has resulted in scientific growth in not only knowledge, but in communication. Thank you Jagan. Lastly, I would like to thank my friends and family who supported me throughout the rollercoaster that is grad school. During my time as a PhD student, I got married, bought a house, adopted a dog, and had a wonderful child. It goes without saying that balancing everything was not always easy. With that I would like to dedicate this dissertation to my anchors, my wife Katherine and son Yareev. 4 Contents Abstract ........................................................................................................................... 8 1 Introduction ................................................................................................................ 10 1 A .1 Innate Animal behavior ................................................................................. 11 1 A.2 Olfaction ........................................................................................................ 19 1 A.3 Caenorhabditis elegans as a Model .............................................................. 25 1 A.4 Conclusion ..................................................................................................... 41 1 B Chemical Mating Cues (Chute and Srinivasan 2014) .......................................... 43 1 B.1 Introduction .................................................................................................... 44 1 B.2 Evidence of pheromone mating cue(s) in C. elegans .................................... 45 1 B.3 Identification and characterization of male specific attractant cues ............... 49 1 B.4 Chemical cues attracting hermaphrodites ..................................................... 55 1 B.5 Conclusions and Future directions ................................................................ 60 References ................................................................................................................. 64 2 Primary Detection of osasa#9 .................................................................................... 83 2 A Co-option of neurotransmitter signaling for inter-organismal communication in C. elegans ...................................................................................................................... 84 2 A.1 Introduction .................................................................................................... 85 2 A.2 Results .......................................................................................................... 87 2 A.3 Discussion ................................................................................................... 109 5 2 A.4 Methods....................................................................................................... 114 2 B Additional behavioral parameters of osas#9 ......................................................... 133 2 B.1 TYRA-2 and osas#9 signaling ..................................................................... 133 2 B.2 Signaling compounds necessary for osas#9 response. .............................. 140 2 B.3 Further behavioral paradigms ...................................................................... 145 2 B.4 Discussion ................................................................................................... 150 2 B.5 Methods....................................................................................................... 154 References ............................................................................................................... 159 3 Attenuation of osas#9 response by E. coli extract .................................................... 172 3A Processing of Sensory Stimuli is Complex and Modular .................................... 174 3A.1 Divergent functions within a neuronal class ................................................. 174 3A.2 Modulation .................................................................................................... 181 3A.3 Multisensory Integration ............................................................................... 186 3B Multisensory integration of osas#9 and E. coli .................................................... 188 3B.1 Introduction ................................................................................................... 188 3B.2 osas#9 behavioral aversion is attenuated by E. coli extract ......................... 190 3B.3 Deciphering the E. coli Attenuation of osas#9 Circuit ................................... 199 3B.4 Discussion and Model .................................................................................. 210 3B.5 Conclusion ...................................................................................................

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