Uri Manor is the Faculty Director of the Goeddel Family Technology Sandbox and Assistant Professor of Cell & Developmental biology at the University of California, San Diego School of Biological Sciences. The Manor Lab develops new methods and tools for studying cellular dynamics with nanometer precision (a sheet of paper is about 100,000 nanometers thick). This includes artificial-intelligence-based computational approaches (deep learning) that integrate data from microscopes to increase image resolution, sensitivity, and collection speed beyond what’s possible with any other existing method. The Manor Lab also develops new imaging, genetic, and molecular tools that facilitate the monitoring and manipulation of cellular structures implicated in diseases including neurodegenerative diseases and hearing loss. Using these advanced technologies, the Manor Lab connects structure to function. Their research advances scientists’ understanding of these cellular processes and ultimately helps discover and create new therapies for treating these conditions.

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Psychedelic Drugs Induce the Formation of New Synapses in the Cochlea

Age-related hearing loss (ARHL) affects hundreds of millions of people. One of the earlier stages of ARHL is synaptopathy, the deterioration of connections, called synapses, between sensory hair cells and spiral ganglion neurons (SGNs) within the inner ear. Synaptopathy disrupts the transmission of auditory signals to the brain. Currently, no approved medications exist for synaptopathy, representing a significant gap in treatment options. Recent studies have shown the potential of psychedelic drugs to stimulate the creation of new synapses (synaptogenesis) in the brain. This led us to investigate their potential effects on the auditory system, given the crucial role of synaptopathy in ARHL.
We first examined the expression of 5-HT2 receptors, known to interact with psychedelics, in the mouse cochlea. We then administered classic psychedelic compounds to healthy adult mice and to SAMP8 mice, a strain that experiences accelerated hearing loss and synaptopathy. Advanced imaging techniques allowed us to quantify synapse numbers in treated mice compared to those receiving a placebo. We also assessed changes to in vivo synaptic function by measuring auditory brainstem response (ABR) Wave I amplitudes.
Our analysis revealed a strong presence of 5-HT2 receptors in SGNs. Importantly, administering psychedelics led to an increase in synapses both within the cochlea and the cortex. Furthermore, we observed a significant increase in ABR Wave I amplitudes, suggesting enhanced synaptic transmission. This was accompanied by an increase in cochlear synapses. We also noted increased neurito-/dendritogenesis in SGN cultures treated with these compounds, indicating a direct impact on SGNs.
These findings demonstrate the capacity of psychedelics to promote synapse formation in the cochlea, suggesting a potential therapeutic role for ARHL and other forms of synaptopathy. The presence of 5-HT2 receptors in SGNs, the observed increase in synapses and synaptic transmission, and the direct effects on SGNs all support this possibility. Further research using mouse models will help clarify the therapeutic potential of psychedelics for hearing restoration. This research offers hope for millions suffering from hearing loss and expands the potential applications of psychedelics