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The Sherlock Holmes (SH) Project is a collaborative problem-solving activity in the form of a murder mystery that is a great resource for upper-level undergraduate courses in neurophysiology that emphasize synaptic transmission and neuromuscular communication. This project, originally described by Adler and Schwartz (2006), has become a central focus of the Neurophysiology course at Allegheny College, along with many complementary activities that work to reinforce the neuroscience material and skills such as creative experimental design and analysis. Active Learning research in advanced levels of undergraduate courses is rare in the pedagogy literature, and this paper adds to that body of research. Formal assessment of the course generally and the SH Project specifically support the hypothesis that the active learning pedagogical strategies employed foster a positive and successful learning environment., (Copyright © 2024 Faculty for Undergraduate Neuroscience.)

Hyperactivity of serotonin 3 receptors (5-HT 3 R) underlies pathologies associated with irritable bowel syndrome and chemotherapy-induced nausea and vomiting. Setrons, a class of high-affinity competitive antagonists, are used in the treatment of these conditions. Although generally effective for chemotherapy-induced nausea and vomiting, the use of setrons for treating irritable bowel syndrome has been impaired by adverse side effects. Partial agonists are now being considered as an alternative strategy, with potentially less severe side effects than full antagonists. However, a structural understanding of how these ligands work is lacking. Here, we present high-resolution cryogenic electron microscopy structures of the mouse 5-HT 3A R in complex with partial agonists (SMP-100 and ALB-148471) captured in pre-activated and open-like conformational states. Molecular dynamics simulations were used to assess the stability of drug-binding poses and interactions with the receptor over time. Together, these studies reveal mechanisms for the functional differences between orthosteric partial agonists, full agonists and antagonists of the 5-HT 3A R., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)