Stanford Advisors

All Publications

  • MDMA enhances empathy-like behaviors in mice via 5-HT release in the nucleus accumbens. Science advances Rein, B., Raymond, K., Boustani, C., Tuy, S., Zhang, J., St Laurent, R., Pomrenze, M. B., Boroon, P., Heifets, B., Smith, M., Malenka, R. C. 2024; 10 (17): eadl6554


    MDMA (3,4-methylenedioxymethamphetamine) is a psychoactive drug with powerful prosocial effects. While MDMA is sometimes termed an "empathogen," empirical studies have struggled to clearly demonstrate these effects or pinpoint underlying mechanisms. Here, we paired the social transfer of pain and analgesia-behavioral tests modeling empathy in mice-with region-specific neuropharmacology, optogenetics, and transgenic manipulations to explore MDMA's action as an empathogen. We report that MDMA, given intraperitoneally or infused directly into the nucleus accumbens (NAc), robustly enhances the social transfer of pain and analgesia. Optogenetic stimulation of 5-HT release in the NAc recapitulates the effects of MDMA, implicating 5-HT signaling as a core mechanism. Last, we demonstrate that systemic MDMA or optogenetic stimulation of NAc 5-HT inputs restores deficits in empathy-like behaviors in the Shank3-deficient mouse model of autism. These findings demonstrate enhancement of empathy-related behaviors by MDMA and implicate 5-HT signaling in the NAc as a core mechanism mediating MDMA's empathogenic effects.

    View details for DOI 10.1126/sciadv.adl6554

    View details for PubMedID 38657057

  • Selective control of synaptically-connected circuit elements by all-optical synapses. Communications biology Prakash, M., Murphy, J., St Laurent, R., Friedman, N., Crespo, E. L., Bjorefeldt, A., Pal, A., Bhagat, Y., Kauer, J. A., Shaner, N. C., Lipscombe, D., Moore, C. I., Hochgeschwender, U. 1800; 5 (1): 33


    Understanding percepts, engrams and actions requires methods for selectively modulating synaptic communication between specific subsets of interconnected cells. Here, we develop an approach to control synaptically connected elements using bioluminescent light: Luciferase-generated light, originating from a presynaptic axon terminal, modulates an opsin in its postsynaptic target. Vesicular-localized luciferase is released into the synaptic cleft in response to presynaptic activity, creating a real-time Optical Synapse. Light production is under experimenter-control by introduction of the small molecule luciferin. Signal transmission across this optical synapse is temporally defined by the presence of both the luciferin and presynaptic activity. We validate synaptic Interluminescence by multi-electrode recording in cultured neurons and in mice in vivo. Interluminescence represents a powerful approach to achieve synapse-specific and activity-dependent circuit control in vivo.

    View details for DOI 10.1038/s42003-021-02981-7

    View details for PubMedID 35017641