University of Pennsylvania
3D Tissue-engineered testbed for in vitro assessment of psychedelic effects on hippocampal circuitry
Introduction: Psychedelics acutely disrupt activity in select brain regions, such as the hippocampus. Clinical and animal studies do not permit robust assessment of cellular or molecular hypothesis and are low-throughput. 2D hippocampal cultures fail to recapitulate the morphological and functional characteristics of endogenous networks. In this study, we engineer 3D hippocampal aggregates with E17 rat tissue and explore its potential as an in vitro testbed for psychedelic compounds . Materials and Methods: The morphological and functional characteristics were assessed at 7, 14, 21, and 28 DIV using immunofluorescent (IF) confocal microscopy and multi-electrode arrays (MEAs). At 14 DIV, cultures were treated with hallucinogenic, 10 uM, or sub-hallucinogenic, 1 uM, concentrations of ketamine. Results and Discussion: Morphologically, aggregates recapitulate in vivo axonal architectures and stellate astrocyte-domain formation. Electrophysiology of aggregates revealed in vivo-like theta/ripple oscillatory activity, network bursting, and sharp-wave ripple patterns, which were absent in 2D cultures . At 10 uM and 1uM, ketamine decreased mean firing rate and burst duration of 2D cultures; yet, in vivo studies suggest ketamine should increase activity in the hippocampus . Thus, 2D hippocampal cultures do not accurately model in vivo functionality. Aggregates recapitulated of in vivo functionality and are expected to provide more translatable results. Conclusions: Hippocampal aggregates mimic in vivo hippocampal neural networks morphologically and functionally. This model can advance our understanding of how different psychedelic compounds effect hippocampal networks and serve as a robust toxicology testbed. Funding: This work is supported by the National Science Foundation Graduate Research Fellowship Program
I am a Bioengineering PhD candidate in Dr. Kacy Cullen’s lab at the University of Pennsylvania. My thesis work is focused on the development of 3D tissue-engineered test bed for psychedelic compounds and assessing the therapeutic capacity for psychedelics to attenuate chronic inflammation in traumatic brain injury. Moreover, I am a co-founder of the Penn Society for Psychedelic Science, which aims to build an multi-disciplinary academic community at Penn and am currently the Executive Director. I also co-organized the Intercollegiate Psychedelic Summit (IPS) 2019 at UPenn, which hosted 8 speakers and 150 attendees. After IPS 2019, I co-founded the Intercollegiate Psychedelic Network (IPN), which has 22 chapters internationally, an academic psychedelic research organization. I am leading IPN efforts to establish a Research Experience for Undergraduates, which would facilitate professional development for students and increase minority representation. I am also co-organizing the Intercollegiate Psychedelic Summit 2020 at Harvard University.