Robyn Michele St. Laurent

All Publications

• Intercalated amygdala dysfunction drives avoidance extinction deficits in the Sapap3 mouse model of obsessive-compulsive disorder. Biological psychiatry St Laurent, R., Kusche, K. M., Rein, B., Raymond, K. B., Kreitzer, A. C., Malenka, R. C. 2024

  Abstract

  The avoidance of aversive stimuli through negative reinforcement learning is critical for survival in real-world environments, which demand dynamic responding to both positive and negative stimuli that often conflict with each other. Individuals with obsessive-compulsive disorder (OCD) commonly exhibit impaired negative reinforcement and extinction, perhaps involving deficits in amygdala functioning. An amygdala subregion of particular interest is the intercalated nuclei of the amygdala (ITC) which has been linked to negative reinforcement and extinction, with distinct clusters mediating separate aspects of behavior. This study focuses on the dorsal ITC cluster (ITCd) and its role in negative reinforcement during a complex behavior that models real-world dynamic decision making.We investigated the impact of ITCd function on negative reinforcement and extinction by applying fiber photometry measurement of GCamp6f signals and optogenetic manipulations during a platform-mediated avoidance task in a mouse model of OCD-like behavior: the Sapap3-null mouse.We find impaired neural activity in the ITCd of male and female Sapap3-null mice to the encoding of negative stimuli during platform-mediated avoidance. Sapap3-null mice also exhibit deficits in extinction of avoidant behavior, which is modulated by ITCd neural activity.Sapap3-null mice fail to extinguish avoidant behavior in platform-mediated avoidance, due to heightened ITCd activity. This deficit can be rescued by optogenetically inhibiting ITCd during extinction. Together, our results provide insight into the neural mechanisms underpinning negative reinforcement deficits in the context of OCD, emphasizing the necessity of ITCd in responding to negative stimuli in complex environments.

  View details for DOI 10.1016/j.biopsych.2024.10.021

  View details for PubMedID 39491639

• 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

  Abstract

  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

  Abstract

  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