Research
My
Rein B, Raymond KB, Boustani C, Tuy S, Zhang J, St. Laurent R, Pomrenze MB, Boroon P, Heifets B, Smith ML, Malenka RC (2024). MDMA enhanes empathy-like behaviors in mice via 5-HT release in the nucleus accumbens. Science Advances.
SUMMARY: MDMA, a drug also known as "Molly" or "ecstasy," can make people feel more connected to others. For decades, scientists have sought to understand how the drug enhances empathy in the brain, thought it's proven difficult to track down. In this study, we looked at how mice react to each other's pain and how MDMA can change this behavior. We found that when mice were given MDMA, they became more sensitive to the pain of other mice. This suggests that MDMA can increase an empathy-like behavior in mice. We also discovered that a specific part of the brain, the nucleus accumbens (NAc), plays a key role in this effect. When we stimulated the release of serotonin this area of the brain (something that MDMA does), we saw the same increase in empathy as when we gave the mice MDMA. This suggests that serotonin release in the NAc is important for MDMA's effects. Finally, we tested MDMA on mice with an autism-linked gene mutation. While these mice showed trouble with responding to the emotions of other mice, both MDMA and stimulating the NAc could enhance the empathy-like behavior in these mice.
Our study shows that MDMA can increase empathy and that serotonin in the NAc is a key factor in this process.
St Laurent R, Kusche K, Rein B, Raymond KB, Kreitzer A, Malenka RC (2024). Intercalated amygdala dysfunction drives avoidance extinction deficits in the Sapap3 mouse model of obsessive-compulsive disorder. Biological Psychiatry.
SUMMARY: People with obsessive-compulsive disorder (OCD) may struggle to avoid harmful things. This study focused on the role of a brain area called the intercalated nuclei of the amygdala (ITC), studying its function in a genetic mouse model of OCD. We found that the OCD mouse model showed dysfunction in the ITC, leading to poor responses to negative stimuli and difficulty forgetting fear. By turning off the ITC using optogenetics, the mice could better overcome their fear. This research highlights the ITCs importance in negative reinforcement and suggests potential avenues for treating OCD.
Tavares M, Rein B (2024). The virtual disengagement hypothesis: A neurophysiological framework for reduced empathy on social media. Cognitive, Affective, and Behavioral Neuroscience.
SUMMARY: As a content creator on social media & a neuroscientist studying empathy, I noticed something troubling: people seem to be less empathetic online. In this paper, we present a new theory: the "Virtual Disengagement Hypothesis" which proposes that the brain's empathy systems are not as engaged during online interactions. We present the evidence to support our theory; for example, virtual interactions lack social cues like facial expressions and vocal tone which help us understand and share others' emotions. This diminished empathy could explain why people behave inconsiderately online. We advocate for future studies pairing brain imaging with social media-relevant behavioral tests. By understanding how our brains are affected by social media, we may develop strategies for promoting more positive online behavior.
Rein B, (2023). Making Science Education More Accessible: A Case Study of TikTok's Utility as a Science Communication Tool. Neuroscience.
SUMMARY: Here I analyzed 150 of my educational videos to understand the factors influencing performance of science content online. I found that the more viewers who liked, shared, and stuck around through the entire video, the more views the video got (as determined by the TikTok algorithm). However, hashtags, sounds, and effects did not impact views. Videos summarizing research papers reached the most viewers, suggesting a demand for accessible scientific information among lay audiences. Moreover, I performed a survey which revealed that 84% of followers feel more trusting of science and scientists after following my account. This suggests that TikTok can serve as an effective platform for promoting scientific literacy and fostering public trust in research. I hope that other science communicators may use these findings to inform future public engagement campaigns.
Rein B*, Jones E*, Tuy S, Boustani C, Johnson JA, Malenka RC, Smith ML (2022). Protocols for the social transfer of pain and analgesia in mice. STAR Protocols.
SUMMARY: Mice can experience pain or pain relief by simply interacting with another mouse experiencing either state. This behavioral test, discovered by Dr. Monique Smith and titled "the social transfer of pain" may thus help researchers understand empathy. Here we present a protocol for other researchers to use, which may enable scientists to further investigate the mechanisms of empathy in animals.
Rein B (2022). Harnessing social media to challenge scientific misinformation. Cell.
SUMMARY: In January 2022, I was at the center of a large open letter written to Spotify, proposing that the platform adopt a misinformation policy. This open letter received international attention, resulting in a series of intense and cataclysmic events. In this paper, I tell the firsthand story of the open letter and the following events as I experienced them.
Conrow-Graham M, Williams J, Martin J, Zhong P, Cao Q, Rein B, Yan Z (2022). A convergent mechanism of high risk factors ADNP and POGZ in neurodevelopment disorders. Brain.
SUMMARY: Autism spectrum disorder (ASD) and intellectual disability are neurodevelopmental conditions with a strong genetic basis. Two genes called ADNP and POGZ have been linked to these conditions. Here we created mice with reduced ADNP or POGZ levels in their prefrontal cortex, finding that they had trouble with certain tasks, showed signs of inflammation in their brains, and impairments in the ability of their brain cells to communicate.
Rapanelli M, Williams J, Ma K, Yang F, Zhong P, Patel R, Kumar M, Qin L, Rein B, Wang ZJ, Kassim B, Javidfar B, Couto L, Akbarian S, Yan Z (2022). Targeting histone demethylase LSD1 for treatment of deficits in autism mouse models. Molecular Psychiatry.
SUMMARY: Here we found that a specific genetic tag called H3K4me2 was less common in the prefrontal cortex of mice with an autism-linked gene mutation. When we administered a drug that increases H3K4me2, the mice became more social and showed restored function of certain brain receptors and genes involved in brain development and communication.
Belin S, Maki BA, Catlin J, Rein B, Popescu GK (2022). Membrane stretch gates NMDA receptors. Journal of Neuroscience.
SUMMARY: NMDA receptors are important for brain development and function. They are usually activated by a chemical called glutamate; however, we found that these receptors can also be activated by mechanical forces, like stretching. We studied NMDA receptors in brain cells and found that stretching them could open them, even without glutamate. This means that mechanical forces can affect how brain cells communicate. Our findings could help us better understand how the brain responds to physical forces and how this affects brain development and function.
Wang, W, Tan T, Cao Q, Zhang F, Rein B, Duan WM, Yan Z (2022). Histone deacetylase inhibition restores behavioral and synaptic function in a mouse model of 16p11.2 deletion. International Journal of Neuropsychopharmacology.
SUMMARY: A small deletion in a region of chromosome 16 can increase the risk of autism spectrum disorder and intellectual disability. Here we found that mice with this deletion showed lower levels of a chemical modification called histone acetylation in their prefrontal cortex. Increasing histone acetylation in these mice restored the activity of neurons in their prefrontal cortex, and enhanced their social and cognitive abilities.
Rein B, Conrow-Graham M, Frazier A, Cao Q, Yan Z (2021). Inhibition of histone deacetylase 5 ameliorates abnormalities in 16p11.2 duplication mouse model. Neuropharmacology.
SUMMARY: A duplication in a region of chromosome 16 can increase the risk of autism spectrum disorder. We previously found that this duplication can affect the function of a gene called NPAS4, which is important for synapse function in the brain. Here we found that a protein called HDAC5 - which can reduce the expression of NPAS4 - is overactive in mice with this genetic duplication. When we blocked HDAC5 function, NPAS4 expression increased, and the mice showed improved social behavior, along with restored synapse function.
Catlin J, Marziali LN, Rein B, Yan Z, Feltri ML, Tooley CS (2021). Age-related neurodegeneration and cognitive impairments of NRMT1 knockout mice are preceded by misregulation of RB and expansion of the neural stem cell population. Cell Death & Disease.
SUMMARY: A protein called NRMT1 is responsible for adding a chemical modification called N-terminal methylation to other proteins. This modification helps regulate how proteins interact with DNA and affects many cellular processes. When we created mice without NRMT1, they had severe developmental problems and aged prematurely. We found that these mice also had problems with their brains, including enlarged ventricles, neurodegeneration in certain brain regions, memory problems, and hyperactivity. These problems were linked to changes in neural stem cells, which are important for brain development. Without NRMT1, these stem cells didn't develop properly, leading to problems later in life. Our findings suggest that NRMT1 plays a crucial role in brain development and function. Problems with NRMT1 could contribute to premature aging and neurodegenerative diseases.
Wang ZJ, Rein B, Zhong P, Williams J, Cao Q, Yang F, Zhang F, Ma K, Yan Z (2021). Autism risk gene KMT5B deficiency in prefrontal cortex induces synaptic dysfunction and social deficits via alterations of DNA repair and gene transcription. Neuropsychopharmacology.
SUMMARY: A gene called KMT5B is linked to autism spectrum disorder. This gene helps add a chemical modification called H4K20me2 to DNA. We studied mice with reduced KMT5B expression in their prefrontal cortex, finding that they had abnormal social behaviors and issues with brain cell communication.
Yan Z, Rein B (2021). Mechanisms of synaptic transmission dysregulation in prefrontal cortex: pathophysiological implications. Molecular Psychiatry.
SUMMARY: The prefrontal cortex (PFC) is a brain region responsible for functions like cognition, planning, and social behavior. Problems with communication between brain cells in the PFC have been linked to mental health disorders like autism, schizophrenia, depression, and Alzheimer's disease. In this review article, we summarize how problems with certain genes, chemicals, and connections between brain cells have been shown to contribute to these conditions.
Zhang F*, Rein B*, Zhong P, Wang ZJ, Yan Z (2021). Synergistic inhibition of histone modifiers produces therapeutic effects in adult Shank3-deficient mice. Translational Psychiatry. [*Equal contribution]
SUMMARY: Autism spectrum disorder (ASD) is a condition that affects social behavior and other aspects of development. Problems with the SHANK3 gene can contribute to ASD. Here we studied mice with a reduced SHANK3 gene and found that they had problems with social behavior and aggression. We treated these mice with a combination of two drugs that affect how genes work in the brain. This treatment helped improve their social behavior and aggression. It also enhanced the function of a specific brain receptor called the NMDA receptor, which is important for cognition and memory. Our findings suggest that this drug combination could be a potential treatment for ASD.
Rein B, Tan T, Yang F, Wang W, Williams J, Zhang F, Mills A, Yan Z. (2020). Reversal of synaptic and behavioral deficits in a 16p11.2 duplication mouse model via restoration of the GABA synapse regulator Npas4. Molecular Psychiatry.
SUMMARY: A duplication in a region of chromosome 16 can increase the risk of autism spectrum disorder, intellectual disability, and schizophrenia. Here we found that mice with this duplication show problems with social behavior and cognition. Furthermore, brain cells in their prefrontal cortex - an area important for social and cognitive functions - weren't communicating properly. When we increased the expression of a gene called NPAS4, the mice's behavioral abnormalities were reversed.
Rein B, Ma K, Yan Z (2020). A standardized social preference protocol for measuring social deficits in mouse models of autism. Nature Protocols.
SUMMARY: Scientists often use a test called the "three-chamber social preference test" to study social behavior in mice. However, there are different ways to do this test, and this can lead to different results. We developed a standardized version of the test that is reliable and sensitive to social behavior. The test has three parts: first, the mouse gets used to the testing chamber. Then, the mouse interacts with two objects. Finally, the mouse interacts with a new mouse and a new object. With this standardized test, scientists can get more accurate and consistent results when studying social behavior in mice with ASD.
Rein B*, Yan Z* (2020). 16p11.2 Copy Number Variations and Neurodevelopmental Disorders. Trends in Neurosciences. (Corresponding author)
SUMMARY: Changes in a region of chromosome 16 can increase the risk of autism spectrum disorder, intellectual disability, and epilepsy. These changes can affect how genes work and lead to problems with brain development. This review discusses the different ways these genetic changes can affect brain function and behavior, and also talks about potential treatments for these conditions.
Rein B, Yan Z, Wang ZJ. (2019). Diminished social interaction incentive contributes to social deficits in mouse models of autism spectrum disorder. Genes, Brain and Behavior.
SUMMARY: One hypothesis for the social changes in autism spectrum disorder is a change in social motivation, however it's unknown whether mouse models of ASD represent this feature. Here we designed a new test to evaluate social motivation in mice. We report that two different mouse models of ASD show reduced motivation to socialize: specifically, they are less willing to enter an uncomfortable environment to spend time with another mouse. This test thus offers a new investigation strategy to study the neurobiological mechanisms of social motivation.
Wang W*, Rein B*, Zhang F, Tan T, Zhong P, Yan Z. (2018). Chemogenetic activation of prefrontal cortex rescues synaptic and behavioral deficits in a mouse model of 16p11.2 deletion syndrome. Journal of Neuroscience. [*Equal contribution]
SUMMARY: A small deletion in a region of chromosome 16 can increase the risk of autism spectrum disorder, and other developmental disorders. Here we find that mice with this deletion have similar behavioral changes to humans with the deletion, and showed hypo-active cell signaling in the prefrontal cortex. When we stimulated neurons in the prefrontal cortex, it improved the cognitive and social behavior of the mice.
Rein BA, McNeil DW, Hayes AR, Hawkins TA, Ng HM, Yura CA. (2018). Evaluation of an avatar-based training program to promote suicide prevention awareness in a college setting. Journal of American College Health.
SUMMARY: Kognito is a training program that helps people learn how to identify and help students who might be at risk for suicide. This study evaluated how effective Kognito is in preparing people to intervene with these students. Over 2,700 college students, faculty, and staff participated in the study. They completed Kognito modules and took surveys before and after the training. The results showed that the training helped people feel more prepared, likely, and confident in their ability to help at-risk students. The training also helped people feel more comfortable assisting LGBTQ and veteran students. Overall, Kognito appears to be an effective way to educate people on how to help at-risk college students.