Simons Center for the Social Brain

SCSB Colloquium Series: Kate O'Connor-Giles, Ph.D.
2022-10-12 16:00 - 17:00 (America/New_York)
Date: Wednesday, October 12, 2022
Hybrid Location: 46-3002 (Singleton Auditorium) and YouTube stream (https://youtu.be/oIT6LYEPXDA)
Speaker: Kate O’Connor-Giles, Ph.D.
Affiliation: Provost’s Associate Professor of Brain Science, Carney Institute for Brain Science and Neuroscience Department, Brown University
Host: Dr. Troy Littleton
Talk title: Genes and their regulation in synapse formation and function
Abstract: Nervous system function requires the integration of diverse neuronal subtypes into the neural circuits that drive thought and behavior. Diverse neuronal fates are specified during development through genetic programs that are the subject of intense study. Despite extensive diversity, all neurons share key features such as chemical synapses. However, it remains largely unknown how gene expression is coordinated to regulate the development of synapses. Our data indicates that synaptic synaptic gene expression is positively and negatively regulated at the level of chromatin accessibility over development. I will present our identification of a gene regulatory network underlying coordinated synaptic gene expression and synapse formation.

SCSB Lunch Series: Seng Bum Michael Yoo, Ph.D.
2022-10-21 12:00 - 13:00 (America/New_York) | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, October 21, 2022
Time: 12:00pm – 1:00pm
Location: SCSB Conference room 46-6011 + Zoom Meeting (https://mit.zoom.us/j/99631032115)
Speaker: Seng Bum Michael Yoo, Ph.D.
Affiliation: Past Simons Postdoctoral Fellow, Mehrdad Jazayeri
Laboratory. Current position: Assistant Professor, Sungkyunkwan University
Host: Dr. Mehrdad Jazayeri
Talk title: Using network models to probe reduced sensitivity to others’ information in observation learning
Abstract: Observational learning is the ability to learn about hidden states of the environment through observing others’ actions and outcomes. Although behavioral and neural signatures of observational learning have been reported, a mechanistic understanding of its underlying neural computations is understudied. Here, we designed a two-player probability reversal-learning task in which both actor and observer need to track the covert change of the reward probability of the options. We find that, even after matching all the information available to each agent, both human and nonhuman primates still learn less from others’ actions and outcomes than their own. We devised a performance-optimized network model to address what types of constraints would bring such suboptimal behavior. Once the model includes independent noise for each agent’s outcome, the model accounted for others’ actions and outcomes to a lesser degree. In sum, the result suggests that asymmetric weights for the action and outcome information would underlie reduced efficacy of observation learning.

SCSB Colloquium Series: Anne E. West, M.D., Ph.D.
2022-10-26 16:00 - 17:00 (America/New_York)
Date: Wednesday, October 26, 2022
Hybrid Location: 46-3002 (Singleton Auditorium) and YouTube stream (https://youtu.be/MOpB8i9ItFw)
Speaker: Anne E. West, M.D., Ph.D.
Affiliation: Professor of Neurobiology, Duke University School of Medicine
Host: Dr. Steven Flavell
Talk title: From chromatin regulation to synapse development in autism and intellectual disability

Abstract: Chromatin-associated proteins are a major class of genes mutated in autism spectrum disorder (ASD) and intellectual disability (ID). These genetic data indicate the importance of gene regulation for brain development, however a significant challenge for the field is to determine how disruptions of chromatin regulators may converge on specific biological processes in developing neurons. We have shown there is extensive chromatin regulation in postmitotic neurons as they mature and form synapses, and we are working to address the hypothesis that ASD/ID mutations in chromatin regulators may act at this late stage of development to disrupt neuronal function. Rahman Syndrome (RMNS) is a rare, genetic form of ID caused by de novo heterozygous mutations in H1-4, which encodes the linker histone H1.4. All RMNS-associated mutations in H1-4 are small insertions or deletions that create a shared C-terminal frameshift. Genetic data indicate that the mutant protein functions in a dominant negative or neomorphic manner to lead to RMNS phenotypes, but the biochemical and cellular consequences of expressing RMNS mutant histone H1.4 are poorly understood. We have found that expressing RMNS mutant histone H1.4 in rat hippocampal neurons leads to the disruption of synaptic gene expression and neuronal firing. We are now undertaking a series of studies to determine when and where histone H1.4 is expressed in the brain during development as a way to understand how the RMNS mutations of H1.4 can lead to ID. As a histone, H1.4 is a direct component of chromatin; thus, studying how mutations in this gene impair neural development offers the opportunity to gain unique and specific biochemical insight into mechanisms of chromatin regulation in neurons.

SCSB Lunch Series: Kohitij Kar, Ph.D.
2022-11-04 12:00 - 13:00 UTC | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, November 4, 2022
Time: 12:00pm – 1:00pm
Location: SCSB Conference room 46-6011 + Zoom Meeting (https://mit.zoom.us/j/99707164021)
Speaker: Kohitij Kar, Ph.D.
Affiliation: Assistant Professor, Faculty of Science, York University (Toronto); Canada Research Chair in Visual Neuroscience; Visiting Scientist at McGovern Institute for Brain Research at MIT (DiCarlo Lab); Research Affiliate at the Center for Brain, Minds and Machines (MIT); Scientific Advisor, BeMe.ai
Host: Dr. Alan Jasanoff
Talk title: Developing a closed-loop framework using artificial neural networks and non-human primate experiments to test theories of atypical visual processing in autistic adults.
Abstract: Despite ample behavioral evidence of atypical sensory processing in autistic individuals, the neural underpinnings of such behavioral heterogeneities remain unclear. To probe these neural mechanisms, I will present our attempts to use a closed-loop framework using rhesus macaques and artificial neural network (ANN) models of the primate ventral visual pathways:

I will demonstrate how we can interchangeably test ANNs, macaques, and human subjects, on the same visual tasks that show behavioral differences in autistic adults.
I will demonstrate how we can generate ANN-based predictions for neurobehavioral markers of autism (related to these tasks) and conduct targeted neural measurements and brain perturbations in rhesus macaques to interrogate and test specific brain circuit related hypotheses.
I will present our first attempts to use ANN-driven approaches to generate more “diagnostic” image sets during human behavioral testing and image-pixel modification based novel behavioral modulation strategies.

SCSB Lunch Series: Sophie Bridgers, Ph.D.
2022-11-18 12:00 - 13:00 (America/New_York) | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, November 18, 2022
Time: 12:00pm – 1:00pm
Location: SCSB Conference room 46-6011 + Zoom Meeting (https://mit.zoom.us/j/96889086712)
Speaker: Sophie Bridgers, Ph.D.
Affiliation: Simons Postdoctoral Fellow, Laura Schulz Laboratory, MIT
Host: Dr. Laura Schulz
Talk title: Loopholes: A window into goal communication and alignment
Abstract: Finding and exploiting loopholes, a possible but unintended interpretation of a rule or request, is a familiar facet of fable, law, and everyday life. A child may respond to their parent who says “It’s time to the put the tablet down” by continuing to play with the tablet after physically putting it down on the floor. Engaging with loopholes requires a nuanced understanding of goals, social ambiguity, and value alignment and offers a new lens through which to examine human communication and cooperation. However, cognitive and computational research on how humans learn to find these creative workarounds remains scarce. In this talk, I will first present a proposal for a formal framework of goal communication that supports intentional misunderstandings. Second, I will share a series of experiments with non-autistic children and adults that (1) reveal loophole behavior emerges around age five and is prevalent and diverse in parent-child and adult-adult interactions, and (2) indicate adults and children evaluate loopholes more leniently than outright non-compliance, as well as predict others exploit loopholes when goals are in conflict but there is a pressure to cooperate. I will also share ongoing work with autistic populations and conclude with a discussion of the development of loophole behavior. This work has implications for improving communication among humans, across developmental and neurodiverse populations, as well as for safer human-AI interactions.​​

SCSB Colloquium Series: Jun Huh, Ph.D.
2022-11-30 16:00 - 17:00 UTC | Singleton Auditorium, Bldg. 46, Room 3002, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Wednesday, November 30, 2022
Hybrid Location: 46-3002 (Singleton Auditorium) and YouTube stream (https://youtu.be/zB3Am6qoVts)
Speaker: Jun Huh, Ph.D.
Affiliation: Associate Professor of Immunology, Harvard Medical School
Host: Dr. Mriganka Sur
Talk title: Maternal gut bacteria dictate offspring’s neurodevelopmental and immune-primed phenotypes.
Abstract: Along with genetic factors, environmental factors are critical contributors to inflammatory disorders such as inflammatory bowel diseases (IBDs) and neurodevelopmental disorders such as autism. Gut microbes are one of these non-genetic factors that define a threshold to either maintaining a homeostatic balance or developing diseases. I will discuss our ongoing efforts to dissect maternal gut microbes’ effects on influencing offspring’s immune and neurodevelopmental phenotypes.

SCSB Lunch Series: Pawan Sinha, Ph.D.
2022-12-02 12:00 - 13:00 (America/New_York) | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, December 2, 2022
Time: 12:00pm – 1:00pm
Location: SCSB Conference room 46-6011 + Zoom Meeting (https://mit.zoom.us/j/98080251233)
Speakers: John Gabrieli, Grover Hermann Professor of Health Sciences and Technology and Cognitive Neuroscience, McGovern Institute, MIT;
Jesse Snedeker, Professor, Department of Psychology, Harvard University;
Pawan Sinha, Professor, Department of Brain and Cognitive Sciences, MIT
Host: Dr. Mriganka Sur
Talk title: Predictive Processes in Autistic and Neuro-typical Individuals

Abstract: Environmental uncertainty presents marked challenges for individuals with autism. Recent theoretical work suggests that autism may impact predictive skills, but empirical findings are mixed across a variety of tasks and participant samples. As part of an ongoing SCSB supported Targeted Project, we have undertaken a set of interlocking studies at MIT and Harvard that assess predictive skills across a broad range of perceptual, cognitive, and linguistic domains, employ behavioral as well as brain measures (EEG and fMRI), and are conducted with children and adults to allow for a developmental analysis of findings. We shall present an update on the results so far which point to a nuanced interpretation of the predictive challenge hypothesis, in contrast to a domain-general compromise of such processes.

SCSB Colloquium Series: Michael Long, Ph.D.
2022-12-14 16:00 - 17:00 (America/New_York)
Date: Wednesday, December 14, 2022
Location: 46-3002 (Singleton Auditorium) and YouTube Stream (https://youtu.be/HMZ3uy2r9GM)
Speaker: Michael A. Long, Ph.D.
Affiliation: Thomas and Suzanne Murphy Professor of Neuroscience, New York University School of Medicine
Host: Dr. Ev Fedorenko
Talk title: Neural mechanisms of interactive communication
Abstract: Vocal communication is central to our everyday lives, facilitating social exchange. Despite significant recent discoveries, the neural mechanisms underlying coordinated vocal exchanges remain poorly understood. We examine the brain processes involved in interactive vocal behaviors, focusing on forebrain circuitry in the human brain as well as a new rodent model for vocal communication. We identify brain activity in key regions in both species and demonstrate that these dynamics are critical for interactive vocalizations.

SCSB Lunch Series: Temporal expectation in marmosets
2023-02-10 12:00 - 13:00 UTC | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, February 10, 2023
Time: 12:00pm – 1:00pm
Location: SCSB Conference room 46-6011 + Zoom Meeting (https://mit.zoom.us/j/93895393648)
Speaker: Shreya Mahajan
Affiliation: Mriganka Sur Laboratory, MIT
Host: Dr. Mriganka Sur
Talk title: Temporal expectation in marmosets
Abstract: Temporal expectation is the ability to use information from past events to predict their occurrence in the future, which allows the allocation of appropriate sensory resources in preparation for the event. Problems with time perception have been linked to several behavioral and cognitive impairments in individuals with autism spectrum disorders. We are investigating how the brain acquires temporal expectation, using a marmoset as an animal model. We trained freely behaving marmosets to perform a simple touchscreen-based timing task, and recorded reaction times and intracranial electroencephalogram (EEG) activity from 4 brain regions, as they were trained from a naïve state until they attained expertise. The behavioral change from the naïve state to the expert was well described with a hazard rate model. A trial by trial analysis of EEG data revealed a significant increment in EEG activity corresponding to anticipation of different events during the task, most prominently before reward delivery. These increments also noticeably changed across sessions as the animal acquired the temporal expectation model. Additionally, significant correlations were seen between the reaction times and the activities from the right parietal and the frontal regions during stimulus presentation period. Thus, the acquisition and representation of temporal expectation engages widespread cortical regions, with specific loci representing specific epochs of the task.

SCSB Colloquium Series: Understanding somatosensory circuit alterations in autism spectrum disorder
2023-02-15 16:00 - 17:00 UTC | Singleton Auditorium, Bldg. 46, Room 3002, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Wednesday, February 15, 2023
Location: 46-3002 (Singleton Auditorium) and YouTube Stream (https://youtu.be/us4cepD9jPs)
Speaker: Lauren Orefice, Ph.D.
Affiliation: Assistant Professor, Massachusetts General Hospital / Harvard Medical School
Host: Dr. Polina Anikeeva
Talk title: Understanding somatosensory circuit alterations in autism spectrum disorder
Abstract: Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder, and surprisingly, the majority of individuals with ASD exhibit altered sensitivity to light touch. Our findings reveal that dysfunction of peripheral somatosensory neurons, not neurons in the brain, causes tactile over-reactivity in ASD models, and this tactile over-reactivity contributes to aberrant social behaviors in mice. We have found that some ASD-related behaviors can be improved with peripherally restricted pharmacological approaches in mouse models. I will present ongoing work about the mechanisms through which peripheral somatosensory neuron dysfunction leads to changes in cortical development, ultimately resulting in altered somatosensation and social behaviors.

SCSB Lunch Series: Child-directed listening: How adults understand what young children say
2023-02-24 12:00 - 13:00 UTC | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, February 24, 2023
Time: 12:00pm – 1:00pm
Location: SCSB Conference room 46-6011 + Zoom Meeting (https://mit.zoom.us/j/91754454830)

Speaker: Stephan Meylan, Ph.D.
Affiliation: Postdoctoral Associate, MIT Brain and Cognitive Sciences, Computational Psycholinguistics Lab
Talk title: Child-directed listening: How adults understand what young children say
Abstract: Research on child language acquisition has traditionally focused on children’s cognitive processes. However, early communication and coordination also depends on the cognitive processes of adult caregivers, as they must infer what children are trying to communicate even when children’s early speech differs substantially from adult speech. In this talk, I will show how a suite of hybrid Bayesian / neural network models of spoken word recognition can help us understand how adults do this. These models reveal that adults rely minimally on the acoustic signal produced by children, and instead heavily depend on prior beliefs about what children are likely to say, along with contextual cues. I’ll show some of the differences between adult word recognition of the speech of typically-developing children and the one child in the sample with an ASD diagnosis; finally, I’ll conclude by discussing the consequences of positing an inferentially-powerful adult listener for theories of first language acquisition.

SCSB Colloquium Series: Memory, learning to learn, coordinated and discoordinated control of cognitive representations
2023-03-01 16:00 - 17:00 UTC | Singleton Auditorium, Bldg. 46, Room 3002, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Wednesday, March 1, 2023
Location: 46-3002 (Singleton Auditorium) and YouTube Stream (https://youtu.be/I98V_gZ4H2w)
Speaker: André Fenton, Ph.D.
Affiliation: Professor, and Director, Center for Neural Science, New York University
Host: Dr. Matthew Wilson
Talk title: Memory, learning to learn, coordinated and discoordinated control of cognitive representations
Abstract: Biological neural networks can represent information in the collective action potential discharge of neurons, and store that information amongst the synaptic connections between the neurons that both comprise the network and govern its function. The strength and organization of synaptic connections adjust during learning, but many cognitive neural systems are multifunctional, making it unclear how continuous activity alternates between the transient and discrete cognitive functions like encoding current information and recollecting past information, without changing the connections amongst the neurons. This lecture will summarize our investigations of mutant mice that model the genetic defect in Fragile X syndrome (FXS), the most common genetic cause of autism and intellectual disability. I then describe our investigations of the molecular and biochemical mechanisms that change synaptic function to persistently store spatial memory in the rodent hippocampus. I will then report on how entorhinal cortex-hippocampus circuit function changes during cognitive training that creates memory, as well as learning to learn in mice. I will describe how the hippocampus system operates like a competitive winner-take-all network, that, based on the dominance of its current inputs, self organizes into either the encoding or recollection information processing modes. We find no evidence that distinct cells are dedicated to those two distinct functions, rather activation of the hippocampus information processing mode is controlled by a subset of dentate spike events within the network of learning-modified, entorhinal-hippocampus excitatory and inhibitory synapses. I will close by reexamining the findings from the FXS mutant mouse.

SCSB Colloquium Series: Flexible generalization in autism and language
2023-03-15 16:00 - 17:00 UTC | Singleton Auditorium, Bldg. 46, Room 3002, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Wednesday, March 15, 2023
Location: 46-3002 (Singleton Auditorium) and YouTube Stream (https://youtu.be/KFnyDlrab5w)
Speaker: Adele Goldberg, Ph.D.
Affiliation: Professor, Princeton University, Psychology Department, Programs in Linguistics, Cognitive Science, NLP
Host: Dr. Roger Levy
Talk title: Flexible generalization in autism and language
Abstract: Converging evidence from linguistics, psychology, and machine learning has led to a growing recognition that words and grammatical constructions are learned by flexibly categorizing over witnessed examples. This suggests a particular cognitive factor should impact the learning and use of language: skill in flexibly extending categories. Given prior findings that autistic individuals tend to display more veridical, less flexible categorization in the perceptual domain, we hypothesized that the same tendency in the cognitive domain would impact autistic individuals’ language. Two completed studies confirm that autistic children and adults underperform their neurotypical peers in language tasks that benefit from flexible meaning extension while performing comparably or better than the neurotypicals on related language tasks that did not require flexible categorization. The next step is to test an intervention aimed at jump-starting early word learning in young autistic children by drawing their attention to a particularly useful type of early meaning extension.

SCSB Lunch Series: The consequence of dysfunctional mitochondria in Rett Syndrome astrocytes
2023-03-24 12:00 - 13:00 UTC | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, March 24, 2023
Time: 12:00pm – 1:00pm
Location: SCSB Conference room 46-6011 + Zoom Meeting (https://mit.zoom.us/j/92171523539)
Speaker: Danielle Tomasello, Ph.D.
Affiliation: Postdoctoral Fellow, Rudolf Jaenisch Laboratory, Whitehead Institute for Biomedical Research
Talk title: The consequence of dysfunctional mitochondria in Rett Syndrome astrocytes
Abstract: The brain requires an incredible amount of energy to function compared to other organs. In addition to roles in neurogenesis and synaptic growth and pruning, astrocytes supply essential metabolites and transfer their own mitochondria to neurons. This fundamental mechanism raises further questions on non-cell autonomous contribution of astrocytes in Rett Syndrome, a severe neurodevelopmental disorder. I will discuss how mutations in MECP2 impact mitochondrial dynamics and energy metabolism in human stem cell-derived astrocytes in 2D culture and 3D cerebral organoids. I will define the mechanisms behind mitochondrial deficits, and how transfer of these dysfunctional mitochondria impact neuronal activity. We do not fully understand the impact of MECP2 mutations on gene expression and chromatin landscapes in the human brain, and how MECP2 functions as the brain develops. To address these areas, I used a multiomics approach on Rett Syndrome cerebral organoids which uncovered novel findings into how MECP2 function greatly differs between neurons and glia in the developing human brain.

SCSB Colloquium Series: The Social Origins of Language and Thought
2023-04-05 16:00 - 17:00 (America/New_York) | Singleton Auditorium, Bldg. 46, Room 3002, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Wednesday, April 5, 2023
Location: 46-3002 (Singleton Auditorium) and YouTube Stream (https://youtu.be/B8gSpIoEpjQ)
Speaker: Robert Seyfarth, Ph.D.
Affiliation: Emeritus Professor of Psychology, University of Pennsylvania
Host: Dr. Ev Fedorenko
Talk title: The Social Origins of Language and Thought
Abstract: In humans, thought and language have evolved together. The same holds for monkeys and apes. Yet compared to humans, nonhuman primates present us with a dilemma: they have a relatively small repertoire of calls but live for years in complex societies where individuals use communication and cognition to establish and maintain their social relations. How do they manage? What do they know about the relations among their companions, and what does their social knowledge tell us about the origins of human language and thought?

SCSB Colloquium Series: Rett syndrome: Are we on a path to a disease modifying treatment?
2023-04-19 16:00 - 17:00 UTC | Singleton Auditorium, Bldg. 46, Room 3002, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Wednesday, April 19, 2023
Location: 46-3002 (Singleton Auditorium) and YouTube Stream (https://youtu.be/mzG8H9WYRfc)
Speaker: Gail Mandel, Ph.D.
Affiliation: Senior Scientist, Vollum Institute, Oregon Health & Science University
Hosts: Dr. Guoping Feng and Dr. Chenjie Shen
Talk title: Rett syndrome: Are we on a path to a disease modifying treatment?
Abstract: I will present some new and promising data that points to targeted RNA editing as a potential means to repair and potentially reverse symptoms in a childhood neurological disease. The development of our approach has focused on Rett syndrome, a neurological disease that is caused by de novo loss of function mutations in the gene encoding the transcriptional repressor, Methyl CG binding protein 2 (MECP2). Rett syndrome mouse models are an excellent testing ground for the efficacy of a targeted RNA editing approach to repair mutations at the root source in neural cells. The disorder is specific to the nervous system, and early work has shown that Rett-like symptoms are reversible in mice following MeCP2 restoration at the postnatal symptomatic stage. Our recent findings will be discussed in the context of alleviating, in a new mouse model, a hallmark respiratory symptom that closely replicates the symptom in female Rett syndrome patients.

SCSB Lunch Series: Conversation in the brain
2023-04-28 12:00 - 13:00 UTC | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
February 3, 2020 — McGovern Institute for Brain Research at MIT. Photo by Caitlin Cunningham Photography.
Date: Friday, April 28, 2023
Time: 12:00pm – 1:00pm
Location: SCSB Conference room 46-6011 + Zoom Meeting (https://mit.zoom.us/j/96362078147)
Speaker: Halie Olson, Ph.D.
Affiliation: Rebecca Saxe Laboratory, Department of Brain and Cognitive Sciences, MIT
Talk title: Conversation in the brain
Abstract: Elucidating how the brain processes language, especially during early development, is critical for understanding developmental disorders involving social communication such as autism. Beginning early in life, language is encountered and produced in complex, dynamic, and social contexts – and yet, neural measure typically study language in isolation. We developed a multimodal, child-friendly functional neuroimaging task to allow us to measure language-evoked activation in two contexts: (1) observing two people having a conversation, and (2) observing one person at a time speaking directly to the listener. We first validated this measure in adults, finding robust responses to comprehensible language in both contexts. Canonical language regions did not differentiate between the two contexts, but some theory of mind regions, as well as some right hemisphere homologues of language regions, did respond more strongly to dialogue. In ongoing work, we are using this measure in young children, both as a tool to measure language processing, and as a means to test how language is processed in different social contexts.

SCSB Colloquium Series: Development and neural diversity of septal nuclei
2023-05-10 16:00 - 17:00 UTC | Singleton Auditorium, Bldg. 46, Room 3002, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Wednesday, May 10, 2023
Location: 46-3002 (Singleton Auditorium) and YouTube Stream (https://youtu.be/WpLhcc2OOhE)
Speaker: Corey Harwell, Ph.D.
Affiliation: Associate Professor, Department of Neurology, Eli and Edythe Broad Center of Regeneration Medicine, UCSF
Host: Dr. Mriganka Sur
Talk title: Development and neural diversity of septal nuclei
Abstract: Septal nuclei in the basal forebrain have critical roles in regulating motivational and emotional states including fear, anxiety, and aggression. Dysfunction of septal neurons is believed to contribute to the pathophysiology of various psychiatric and behavioral disorders. The septum can be classified into two regions: the medial septum and the lateral septum. The medial septum is composed of cholinergic, GABAergic and glutamatergic neurons that primarily project to the hippocampus. While the lateral septum is made up of a diverse array of GABAergic projection neurons that have reciprocal connections with several brain regions known to regulate emotion, affect and motivational states. It is currently unclear how septal diversity and circuit wiring are specified during development. We have employed molecular genetic approaches and single-cell/nuclei RNA-seq to systematically assess the extent of septal cell diversity and the developmental logic for the production and wiring of these diverse neural cell types. We will discuss our recent progress in understanding the anatomical organization and functional specialization of neural cell types in the lateral septum.

SCSB Lunch Series: Charactering the molecular architecture of excitatory synapse onto GABAergic interneurons
2023-05-19 12:00 - 13:00 UTC | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, May 19, 2023
Time: 12:00pm – 1:00pm
Location: SCSB Conference room 46-6011 + Zoom Meeting (https://mit.zoom.us/j/99475222915)
Speaker: Menglong Zeng, Ph.D.
Affiliation: Postdoctoral Fellow, Guoping Feng Laboratory, McGovern Institute, MIT
Talk title: Charactering the molecular architecture of excitatory synapse onto GABAergic interneurons
Abstract: Normal brain function requires a delicate balance between excitatory and inhibitory neurons. While only representing a small population of all neurons, GABAergic interneurons are essential to maintaining functional homeostasis across the brain. Genes encoding excitatory synaptic proteins tend to be one of the most prevalent hits in the screens of autism risk genes. However, the molecular architecture of excitatory synapses onto GABAergic interneurons has not been studied in sufficient details to establish the mechanistic insights needed to improve our understanding and treatment of autism.
In our study, we applied spatiotemporally precise proximity labeling techniques to uncover a novel assemblage of excitatory synaptic proteins onto parvalbumin interneurons. We discovered that parvalbumin interneurons have several strategies to distinguish their excitatory synapses molecularly and functionally from pyramidal neurons, possibly implicated in autism pathogenesis. We also combined gene editing, expansion microscopy and electrophysiology to study the structure and function of minority cell-type specific synapses within an intact circuit, to address the hypothesis that aberrant excitatory synaptic input onto interneurons contribute to neural circuit dysfunction in autism.

SCSB Lunch Series: Advanced Genetic Therapies for the Treatment of Rett Syndrome
2023-07-31 08:00 - 17:00 UTC
Date: Friday, September 29, 2023
Time: 12:00pm – 1:00pm
Location: SCSB Conference room 46-6011 + Zoom Meeting (https://mit.zoom.us/j/92352928861)
Speaker: Chenjie Shen, Ph.D.
Affiliation: Postdoctoral Fellow, Guoping Feng Laboratory, McGovern Institute, MIT
Talk title: Advanced Genetic Therapies for the Treatment of Rett Syndrome
Abstract: Despite genome editing technologies have made unprecedented advances during the past decade, therapeutic use of genome editing in the CNS is still in its infancy. Rett syndrome is a neurodevelopmental disorder caused by genetic mutations in a X-linked gene named MECP2. The clinical progression of current gene replacement-based therapies encounters significant challenges owing to the dosage sensitivity of MeCP2. To overcome these challenges and facilitate the translation to human applications, 1). We explored various genetic therapeutic approaches for the most prevalent mutations found in RTT patients, including DNA/RNA base editing and sup-tRNA translational readthrough, aiming to restore MECP2 expression in vivo under its endogenous control. 2). We developed several MeCP2 humanized mouse models and generated iPSCs-derived human neurons to meticulously assess the effectiveness and safety of diverse genetic therapies. 3). We established a highly efficient genome editing method for generating knock in marmoset models that harbor human MeCP2 mutation, which will greatly facilitate study of primate-specific brain mechanisms in Rett Syndrome as well as testing and honing of various genetic therapies for effective genome editing and delivery of genetic medicine.

SCSB Lunch Series: Observational learning in the macaque brain
2023-09-08 12:00 - 13:00 UTC | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, September 8, 2023
Time: 12:00pm – 1:00pm
Location: SCSB Conference room 46-6011 + Zoom Meeting (https://mit.zoom.us/j/95884128103)
Speaker: Ruidong Chen, Ph.D.
Affiliation: Simons Postdoctoral Fellow, Mehrdad Jazayeri Laboratory, McGovern Institute, MIT
Talk title: Observational learning in the macaque brain
Abstract: Animals make inferences about latent causes from either their own actions and outcomes (experiential learning) or that of others (observational learning). Do animals discount the experience of others relative to their own, even when facing the same amount of external information? Are the neural substrates of experiential and observational learning shared, overlapping, or independent? To reveal and compare the neural mechanisms for belief updates from self-experience and social observations, we designed a two-player social learning task for both human and non-human primates (NHPs). Two NHPs perform this task with human-like behavior, where both actor and observer accumulate evidence over trials to make choices, with observers discounting evidence from actors relative to their own. I will report preliminary findings from ongoing neurophysiology experiments.

SCSB Colloquium Series: Understanding Brain-Behavior Relationships
2023-09-13 16:00 - 17:00 UTC | Singleton Auditorium, Bldg. 46, Room 3002, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Wednesday, September 13, 2023
Location: 46-3002 (Singleton Auditorium) and YouTube Stream (https://youtube.com/live/-PbaB8cx8xQ)

Speaker: R. Todd Constable, Ph.D.
Affiliation: Elizabeth Mears and House Jameson Professor of Radiology and Bioimaging Sciences, Yale University School of Medicine
Host: Dr. Evelina Fedorenko

Talk title: Understanding Brain-Behavior Relationships
Abstract: This talk will explore the use of brain-behavior modeling in understanding brain organization. Focus will center on both aspects of such models. The first aspect is in terms of what the functional organization and how it reconfigures with performance across behavioral tasks tells us about brain organization across the lifespan and how it changes as a function of task. The second aspect is what such models tell us about novel and/or standardized behavioral paradigms that are commonly used. This second aspect will provide insight into the specific networks supporting performance on any given behavioral task and provide information on task combinations that better isolate specific cognitive constructs.

SCSB Lunch Series: Advanced Genetic Therapies for the Treatment of Rett Syndrome
2023-09-29 12:00 - 13:00 UTC | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States

SCSB Colloquium Series: Synapses and Me
2023-10-04 16:00 - 17:00 UTC | Singleton Auditorium, Bldg. 46, Room 3002, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Wednesday, October 4, 2023
Location: 46-3002 (Singleton Auditorium) and YouTube Stream (https://youtube.com/live/lCJGajRrG34)

Speaker: Gerald Fischbach, MD
Affiliation: Distinguished Scientist and Fellow, Simons Foundation
Host: Dr. Mriganka Sur

Talk title: Synapses and Me
Abstract: Throughout my 60 years in biomedical science, I have been focused on chemical synapses in the brain and peripheral nervous system. I began by studying the vertebrate neuromuscular junction. Electrophysiology led to biochemical and genetic analyses focused on how “trophic” factors released from motor nerve terminals regulate the number and distribution of acetylcholine receptors in the postsynaptic muscle membrane. As my lab grew and as I took on more administrative responsibilities, including Chairmanships at Washington University and at Harvard Medical School, Directorship of NINDS and finally Chief Scientist at the Simons Foundation Autism Research Initiative my interests broadened. My research moved up the neural axis from the spinal cord to the midbrain and the cerebral cortex, and my interests grew as well. Molecular, biology systems science and computational approaches are opening new ways of thinking about synapses and behavior. It is simply not enough to say that autism is a “synaptopathy”.
Bio:
Gerald Fischbach joined the Simons Foundation in 2006 to oversee the Simons Foundation Autism Research Initiative (SFARI). He then became the foundation’s first chief scientist and fellow and currently holds the title of Distinguished Scientist and Fellow. He is formerly the dean of the Faculties of Health Sciences at Columbia University, and director of the National Institute of Neurological Disorders and Stroke at the National Institutes of Health from 1998-2001, Fischbach received his M.D. degree in 1965 from Cornell University Medical School and interned at the University of Washington Hospital in Seattle. He began his research career at the National Institutes of Health, serving from 1966-1973. He subsequently served on the faculty of Harvard Medical School, first as associate professor of pharmacology from 1973-1978 and then as professor until 1981. From 1981-1990, Fischbach was the Edison professor of neurobiology and head of the Department of Anatomy and Neurobiology at Washington University School of Medicine. In 1990, he returned to Harvard Medical School where he was the Nathan Marsh Pusey professor of neurobiology and chairman of the neurobiology departments of Harvard Medical School and Massachusetts General Hospital until 1998.
Throughout his career, Fischbach has studied the formation and maintenance of synapses, the contacts between nerve cells and their targets through which information is transferred in the nervous system. He pioneered the use of nerve cell cultures to study the electrophysiology, morphology and biochemistry of developing nerve-muscle and inter-neuronal synapses. His current research is focused on roles that neurotrophic factors play in determination of neural precursor fate, synapse formation and neuronal survival.
Fischbach is a past president of the Society of Neuroscience and serves on several medical and scientific advisory boards. He is a member of the National Academy of Sciences, the American Academy of Arts and Sciences and the Institute of Medicine. He is a fellow of the American Association for the Advancement of Science and a former non-resident fellow of the Salk Institute.

SCSB Lunch Series: Probing Cholinergic Brain Function Using Multimodal Molecular Imaging
2023-10-20 12:00 - 13:00 UTC | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, October 20, 2023
Time: 12:00pm – 1:00pm
Location: SCSB Conference room 46-6011 + Zoom Meeting (https://mit.zoom.us/j/91735453120)
Speaker: Sajal Sen, Ph.D.
Affiliation: Simons Postdoctoral Fellow, Alan Jasanoff Laboratory, MIT
Talk title: Probing Cholinergic Brain Function Using Multimodal Molecular Imaging
Abstract: Autism spectrum disorders (ASD) are a diverse family of neurodevelopmental conditions that lack any consistent biomarkers to date. Cholinesterase (ChE) enzymes, which lyse choline-based esters at cholinergic synapses, have been emerging as a potential therapeutic target in ASDs, and could serve as synapse-specific biomarkers for these disorders. However, probe technologies to correlate ChE activity and ASD are not yet available. Our ongoing research, therefore, seeks to design and validate novel ChE-sensitive MRI contrast agents to probe cholinergic phenotypes in ASD models, facilitate therapy development, and ultimately establish a non-invasive diagnostic tool for the clinical evaluation of autistic patients. Our imaging agent design is based on a previously validated molecular mechanism developed in the Jasanoff lab to detect brain enzyme activity in animal models. The new contrast agent uses a chemical framework that facilitates probing ChE activity via multimodal imaging including MRI and optical methods. This added feature will permit valuable integration of readouts obtained over a range of spatial scales, both in living subjects and postmortem tissue. In this colloquium, I will describe the synthesis and validation of pilot imaging probes in vitro, as well as initial in vivo results using a lead ChE-responsive compound. This work is thus yielding novel tools for autism research, with long-term potential for evaluating cholinergic function in human subjects.

SCSB Colloquium Series: Individual variation in neuroanatomy within autism
2023-10-25 16:00 - 17:00 (America/New_York) | Singleton Auditorium, Bldg. 46, Room 3002, 43 Vassar Street, Cambridge, MA, 02139, United States
Portrait of Assistant Professor Stefano Anzellotti (Psychology) photographed in a classroom and outside of McGuinn for Kalscheur SJ web slide show and a future issue of Welcome Additions in Chronicle.
Date: Wednesday, October 25, 2023
Location: 46-3002 (Singleton Auditorium) and YouTube Stream (https://youtube.com/live/lF-TI7anPZs)
Speaker: Stefano Anzellotti, Ph.D.
Affiliation: Assistant Professor, Boston College
Host: Dr. Rebecca Saxe
Talk title: Individual variation in neuroanatomy within autism
Abstract: Autism spectrum disorder is very heterogeneous. Diagnosed individuals vary in terms of genetics, neural measures, and behavior. Heterogeneity has two important implications for autism research. First, it makes it more difficult to identify findings that replicate, hindering the progress of research. Second, different individuals are likely to need different, personalized interventions. Therefore, understanding individual variation within autism is a key research objective. A major obstacle to this objective is the fact that individual variation related to autism is mixed with unrelated variation, which also occurs in the general population. We find that a recently developed deep learning method — Contrastive Variational Autoencoders — makes it possible to disentangle autism-related individual variation in brain anatomy from variation that is shared with the general population. In turn, this process reveals previously hidden relationships between individual differences in brain anatomy and individual differences in behavioral symptoms. Finally, we use counterfactual AI to identify interpretable anatomical sites of individual variation within autism, associating differences in behavioral symptoms with changes at specific anatomical loci. This approach can also be applied to other data modalities and other disorders, offering a technique to study individual variation specific to a particular population of participants.

SCSB Colloquium Series: Modeling brain overgrowth in autism using human pluripotent stem cells
2023-11-08 16:00 - 17:00 (America/New_York) | Singleton Auditorium, Bldg. 46, Room 3002, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Wednesday, November 8, 2023
Location: 46-3002 (Singleton Auditorium) and YouTube Stream (https://youtube.com/live/4vzPAvJGbfo)
Speaker: Sundari Chetty, Ph.D.
Affiliation: Assistant Professor, Center for Regenerative Medicine, MGH; Department of Psychiatry, Harvard Medical School; Principle Faculty Member, Harvard Stem Cell Institute
Host: Dr. Dara Manoach
Talk title: Modeling brain overgrowth in autism using human pluripotent stem cells
Bio & Abstract: Dr. Sundari Chetty is an assistant professor at the Center for Regenerative Medicine at Massachusetts General Hospital (MGH) and the department of Psychiatry at Harvard Medical School. She also serves as a Principal Faculty member of the Harvard Stem Cell Institute. Dr. Chetty received her PhD in neuroscience and B.A. in molecular and cellular biology from the University of California, Berkeley. Dr. Chetty started her lab at Stanford University after completing her postdoctoral work in Stem Cell and Regenerative Biology at Harvard University in Douglas Melton’s laboratory. In June of 2022, she relocated her laboratory to MGH.
The overarching goal of Dr. Chetty’s lab is to understand the mechanisms underlying neurodevelopmental and psychiatric disorders, such as autism spectrum disorder and schizophrenia, and identify novel therapeutic targets based on these mechanistic insights. In particular, her lab has been investigating the mechanisms underlying brain overgrowth or undergrowth in these disorders using human induced pluripotent stem cell (iPSC) technology. Using human iPSCs from idiopathic patients as well as those with known genetic variations, the Chetty lab uses two-dimensional and brain organoid models to investigate changes at the cellular, functional, and mechanistic levels using a broad range of techniques from RNA sequencing, genome editing, to functional assays in in vitro and in vivo models. This talk will highlight recent work in the Chetty lab investigating how interactions between the neuroimmune system regulate brain overgrowth in autism and other neurodevelopmental disorders.

SCSB Lunch Series: A network of brain areas is sensitive to prosody and distinct from language and auditory areas
2023-11-17 12:00 - 13:00 (America/New_York) | Singleton Auditorium, Bldg. 46, Room 3002, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, November 17, 2023
Time: 12:00pm – 1:00pm
Location: Singleton Auditorium 46-3002 + Zoom Meeting (https://mit.zoom.us/j/93332201270)
Speaker: Tamar Regev, Ph.D.
Affiliation: Postdoctoral Associate, Ev Fedorenko Laboratory, MIT; Fellow of the Poitras Center for Psychiatric Research
Talk title: A network of brain areas is sensitive to prosody and distinct from language and auditory areas
Abstract: Prosody refers to auditory features of speech beyond phonetics, like pitch and tempo, which convey linguistic, emotional, and other socially-relevant information. Does the brain contain specialized areas for processing prosody or is prosodic information processed by known auditory or language areas? Using fMRI, we identified temporal and frontal brain areas which were strongly sensitive to prosody with or without linguistic content. These prosody-sensitive areas were adjacent to but distinct from language areas which extract meaning from linguistic input, and from auditory areas that support pitch perception and speech perception. Interestingly, these areas showed some response to communicative signals, especially facial expressions and non-speech vocalizations. These results suggest that prosody is processed by a network of brain areas that lie in close proximity to language-selective areas and are broadly sensitive to non-linguistic communicative cues. This work lays a critical foundation for further investigations of the neural basis of prosodic processing and its disorders.
Bio: Dr. Tamar Regev is a Postdoctoral Associate at BCS, MIT, working with Prof. Ev Fedorenko, and is a fellow of the Poitras Center for Psychiatric Research. She earned her Ph.D. in Computational Neuroscience from The Hebrew University of Jerusalem, where she was advised by Prof. Leon Y. Deouell and Prof. Israel (Eli) Nelken, and conducted research on representations of auditory frequency using EEG and computational modeling. She holds a M.Sc in Cognitive Systems from UPF, Barcelona, and a B.Sc in Physics and Biology from Tel-Aviv University.

SCSB Colloquium Series: The neurobiology of social isolation
2023-12-06 16:00 - 17:00 UTC | Singleton Auditorium, Bldg. 46, Room 3002, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Wednesday, December 6, 2023
Location: 46-3002 (Singleton Auditorium) and YouTube Stream (https://youtube.com/live/89g148lSIco)
Speaker: Moriel Zelikowsky, Ph.D.
Affiliation: Assistant Professor, Department of Neurobiology, University of Utah
Host: Dr. Steve Flavell
Talk title: The neurobiology of social isolation
Abstract: We are social animals. Extended deprivation of social contact can produce deleterious effects on the brain and behavior. Our group works to identify the neural circuit mechanisms which give rise to the internal brain state produced by prolonged social isolation and its impact on survival-related social behaviors. I will present some of our recent work examining the effects of social isolation on mouse courtship behavior and vocal communication using in-depth behavioral and acoustic analyses, machine vision, genetically-targeted cellular perturbations, and in vivo imaging in mice. Collectively, our findings reveal a dramatic disruption of mouse courtship behavior and social communication after isolation, and identify a unique neural signature in the coding of this brain state.

SCSB Lunch Series: Probing the cortical circuits that prevent sensory overload
2023-12-15 12:00 - 13:00 (America/New_York) | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, December 15, 2023
Time: 12:00pm – 1:00pm
Location: Simons Center Conference room 46-6011 + Zoom Meeting (https://mit.zoom.us/j/96426558759)
Speaker: Alex Major, Ph.D.
Affiliation: Past Simons Fellow, Earl Miller Laboratory, Picower Institute for Learning and Memory, MIT
Talk title: Probing the cortical circuits that prevent sensory overload
Abstract: Sensory overload in autism spectrum disorder (ASD) may result from disrupted filtering of predicted sensory inputs. Our Predictive Coding model of brain function suggests sensory information is carried by gamma rhythms in the upper layers of the cortex. In contrast, alpha/beta rhythms are in deep layers and may suppress gamma rhythms of predicted sensory input. We hypothesize feedback prediction signals in ASD are deficient, manifesting as reduced alpha/beta rhythms. This causes less suppression of incoming sensory input and gamma, leading to sensory overload. We have developed a technique to simulate sensory overload in rhesus monkeys by suppressing deep layers of prefrontal cortex. This is hypothesized to decrease feedback alpha/beta activity and thus disinhibit gamma activity and sensory input. This will directly test a mechanism of sensory overload, perhaps leading research towards improved symptom management.
