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294Lisha Shao, Ph.D.<p>​​​Assistant Professor<br></p>(302) 831-2579shaol@udel.edu281 DBI244 DBI<p></p><ul><li>B.S. – Nankai University</li><li>Ph.D. – Tsinghua University</li><li>Postdoc – Janelia Research Campus, HHMI <br></li></ul><p></p><p>An essential function of the brain reward system is to determine whether something is good or bad, which is of critical importance to an organism's survival and reproduction. The reward pathway has evolved to ensure that meaningful stimuli for animals, such as food, shelter and sex, are perceived as rewarding. Although the mechanisms of sensory detection of these meaningful stimuli have been intensively studied, it remains mysterious how the detected sensory signals are transformed into the perception of reward or valence. <br></p><p>There are usually multiple layers of neurons between peripheral sensory receptors and reward neurons in the central brain. These interconnected intermediate layers are where multisensory integration takes place. It is common in the natural environment that hungry animals hesitate about pursuing food and mates when a predator suddenly appears. The simultaneous valuation of multimodal sensory stimuli is critical to higher cognitive functions, such as decision making and learning. Therefore, these intertwined and undescribed intermediate layers are key to the proper tuning of reward perception by internal states and external stressors. Resolving this knowledge gap will require delineating the anatomy and functional structure of the neural pathways that mediate the transformation of sensory stimuli to reward perception. We will address this question in <em>Drosophila melanogaster</em>, a tractable system with simple brain circuits and an extensive genetic toolbox for neurogenetic and neurocircuitry studies. Specifically, <strong>we will determine how perceived sensory modalities, such as food and sex, are transformed into values by the reward pathways and how this process is tuned by internal states and environmental stresses</strong>. Our ultimate goal is to define the neural architecture and principles by which reward information from different sensory modalities is perceived and processed.<br></p><p><strong>1. Delineate the neural circuit mediating the valence of mating in females</strong></p><p>Animals associate mating with external and internal stimuli and adjust their mating strategy accordingly for best reproductive outcomes. Rejection by females or interruption of copulation significantly suppress a male's motivation to mate in many species. In contrast, animals form appetitive memories with olfactory, visual, or spatial stimuli that are previously associated with successful mating and show stronger motivation and shortened latency to mate when presented with these stimuli. The brain reward system plays an essential role in weighing the valence of the sensory information involved in mating and bias the animal's response to the corresponding sensory information. Previous studies revealed that mating is rewarding to male <em>Drosophila. </em>However, we do not know how mating is represented in reward pathways in females. My lab will answer the following questions. What is the valence of mating in female flies? How is the valence conveyed to and evaluated by the reward circuits? If/how does the valence of mating regulate female fitness?<br></p><p><strong>2. Identify novel reward neurons and determine their relationships with dopamine neurons</strong></p><p>A breakthrough in understanding reward mechanisms was the discovery of dopaminergic molecular pathways and neural circuits. Dopamine neurons (DANs) play versatile roles in reward coding, by responding to reward and punishment directly or responding to a cue associated with these stimuli. With behavioral, imaging, and connectomic approaches, my lab will answer the following questions. How are sensory modalities, such as food, water and sex, transmitted to DANs? How do the animal's internal states regulate DAN's response to reward? Are there reward circuits independent of DANs? <br></p><p><strong>3. Investigate the interaction between stress and reward system</strong></p><p>In the natural environment, an animal's fitness and survival are constantly challenged by the imbalance between available resources and situational demands. Environmental stresses are important regulators of the brain reward system. When stress occurs, the stress reaction system is mobilized to maintain homeostasis and causes a series of physical responses that put the animal in fight-or-flight mode. However, if the stress reaction fails to re-achieve homeostasis or if the stressor becomes chronic, there will be adverse physical and mental outcomes, including depression and addiction. Both acute and chronic stress affect the value representation and processing in reward circuits. My lab will work on the genetic and neural mechanisms of how environmental stressors regulate the reward related behaviors.<br></p><p></p><ul><li><strong>Shao L#</strong>, Chung P, Wong A, Siwanowicz I, Kent CF, Long X, Heberlein U#, A neural circuit encoding the experience of copulation in female Drosophila. (2019) Neuron 102: 1025–1036 (cover story)​</li><li>Zer S, Zak H, <strong>Shao L</strong>, Ben-Shaanan S, Tordjman L, Bentzur A, Shmueli A, Shohat-Ophir G. Triggering ejaculation via the optogenetic activation of male specific corazonin neurons mimics the rewarding value of natural copulation in Drosophila. (2018) Current Biology 28(9): 1445-1452.e3.</li><li>Kim YK, Saver M, Simon J, Kent CF, <strong>Shao L</strong>, Eddison M, Agrawal P, Texada M, Truman JW, Heberlein U. Repetitive aggressive encounters generate a long-lasting internal state in Drosophila melanogaster male. (2018) Proceedings of the National Academy of Sciences USA 115(5): 1099-1104.</li><li><strong>Shao L*#</strong>, Saver M*, Chung P, Ren Q, Lee T, Kent C, Heberlein U#. Dissection of the Drosophila neuropeptide F circuit using a high-throughput two-choice assay. (2017) Proceedings of the National Academy of Sciences USA 114: E8091-E8099.</li><li><strong>Shao L*</strong>, Lu B*, Wen Z, Teng S, et al. Disrupted-in-Schizophrenia-1 (DISC1) protein disturbs neural function in multiple disease-risk pathways. (2017) Human Molecular Genetics 26 (14): 2634-2648.</li><li>Lu B*, <strong>Shao L*</strong>, Feng S, Wang T, Zhong Y. The β-alanyl-monoamine synthase ebony is regulated by schizophrenia susceptibility gene dysbindin in Drosophila. (2014) Science China. Life sciences 57(1): 46-51.</li><li><strong>Shao L</strong>, Zhong Y. Drosophila model of cognitive disorders: Focus on memory abnormality. Chapter 12: Behavioral Genetics of the Fly (Drosophila Melanogaster) (2013) Edition: illustrated, Publisher: Cambridge University Press, Editor: Josh Dubnau, pp.162-176.</li><li><strong>Shao L</strong>, Shuai Y, Wang J, Feng S, Lu B, Li Z, Zhao Y, Wang L, Zhong Y. Schizophrenia susceptibility gene dysbindin regulates glutamatergic and dopaminergic functions via distinctive mechanisms in Drosophila. (2011) Proceedings of the National Academy of Sciences USA 108(46): 18831-18836.</li><li>Liu X, Yuan X, Sun K, Shuai Y, Song Q, Wang L, <strong>Shao L</strong>, et al. Genomic screen for expression pattern in adult Drosophila brains in vivo by enhancer trap method and establishment of expression database. (2008) Progress in Biochemistry and Biophysics 35(6): 645-649.</li></ul><p>* Equal contribution<br># Corresponding author</p><p></p><ul><li><a href="https://shaolab.bio.udel.edu/">https://shaolab.bio.udel.edu</a><br></li></ul><img alt="Lisha Shao" src="/content-sub-site/PublishingImages/people/shaol/shaol_photo.jpg" style="BORDER:0px solid;" />

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