2022/23 Neuroscience Research Colloquium Schedule

FALL 2022

SEPTEMBER 9 – IN PERSON AT RUDY NORTH LECTURE THEATRE 

  • Host: Dr. Erin MacMillan
  • Speaker: Dr. Anke Henning, University of Texas
  • Title: Metabolic MRI at ultra-high fields – from systems architecture to application
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  • Meeting ID: 99412 188589
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Metabolic MRI allows observing energy metabolism, neurotransmission, second messaging, endocrine signaling, antioxidants, protein metabolism and dynamic membrane processes in the human brain. Related quantitative metabolic imaging biomarkers are beneficial for differential diagnostics, monitoring of treatment response and patient stratification in various neurological and psychiatric disorders and yield complementary information to structural and functional imaging. To visualize related metabolic processes my research group develops methodology for highly spatially and temporally resolved metabolic imaging exploiting magnetic resonance spectroscopy (MRS), chemical exchange saturation transfer (CEST) and non-proton spectroscopic imaging (31P, 13C, 2H) at 3T, 7T and 9.4T with application in the human brain, spinal cord and myocardium. These methods allows for non-invasive and non-ionizing determination of tissue concentrations and metabolic turn-over rates of more than 20 metabolites and ions and specifically benefits from ultrahigh field strength with regard to spectral resolution and signal-to-noise ratio.

However, specific physical and technical challenges have to be overcome to fully exploit the advantages of ultrahigh field MR at 7T and 9.4T for human MRI and MRS. Hence my laboratory invests into the development of enabling technology for ultrahigh field MRI including scan hardware such as radiofrequency coils and static magnetic field shimming, numerical optimization of these setups and is able to perform respective safety assessment to allow for application in humans. The lab also develops scan software including MRI sequences and is able to design tailored radiofrequency pulse including such dedicated to parallel transmission systems. Specifically for metabolic MRI we also develop tailored data analysis methods such as image reconstruction, post-processing and quantification pipelines and recently started to explore machine-learning based approaches.

This presentation gives an overview over our recent research activities.

SEPTEMBER 16 – IN PERSON AT RUDY NORTH LECTURE THEATRE 

  • Host: Stefan Wendt
  • Speaker: Dr. Kim Green, University of California, Irvine
  • Title:  Exploring  microglia  function  in  the healthy and Alzheimer’s disease brain
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Microglia are the primary immune cell of the brain, but have roles outside of immunity as well as being implicated in the pathogenesis of many CNS disorders. Here I will show how we can use CSF1R inhibitors to control the microglial population in vivo, and elucidate their functions in both the homeostatic and disease brains. I will focus on the involvement of microglia in Alzheimer’s disease, and also detail several new genetic models to understand the disease progression.

SEPTEMBER 23 – RUDY NORTH LECTURE THEATRE “LIVE” SCREENING 

  • Host: Dr. Vesna Sossi
  • Speaker: Dr. Eugenii A. (Ilan) Rabiner, King’s College, London
  • Title: Molecular Imaging in CNS drug development
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  • Meeting ID: 99412 188589
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Over the past 25 years the costs of drug development have been rising steeply, with later phases being particularly resource intensive. Molecular imaging (primarily PET) has become an indispensable tool in early phase drug development, especially for compounds focused on CNS targets, PET studies conducted at an appropriate enable the refinement of the dose range to be explored in later phase studies, leading to time and resource savings, as well as providing early demonstration of compounds that are going to fail, leading to early termination and the reallocation of considerable resources. This talk will discuss the application of PET and MR imaging in early phase drug development, within the framework of the “three pillars” of drug development and provide examples of such studies.

OCTOBER 14 – IN PERSON AT RUDY NORTH LECTURE THEATRE 

  • Host: Dr. Lynn Raymond
  • Speaker: Dr. Eric Yttri, Carnegie Mellon University
  • Title: Understanding brain-wide circuit dynamics underlying learned and spontaneous behavior with B-SOiD
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For decades, neuroscience has focused almost exclusively on stereotyped, reductionist, and over-trained behaviors due to their ease of study. In contrast, naturalistic behavior provides a rich diversity of movements, but this feature also largely precludes it from quantification and use. Recent advances in computer vision have enabled automatic tracking of the position of body parts – but position is not behavior. To provide a bridge from positions to behaviors and their kinematics, we developed B-SOiD (Hsu and Yttri, Nature Communications). This open-source method discovers natural spatiotemporal patterns in body position data, then uses the cluster statistics to train a machine learning algorithm to classify behaviors that can generalize across subjects and labs. We will discuss the application of this user-friendly algorithm in flies, mice, and humans. Finally, we will share new data from recordings throughout the cortex and basal ganglia that reveal how these diverse behaviors are encoded by single units and interconnected neural populations.

OCTOBER 21 – IN PERSON AT RUDY NORTH LECTURE THEATRE 

  • Host: Dr. Annie Ciernia
  • Speaker: Dr. Anthony Filiano, Duke University
  • Title: Regulating the Brain from Its Borders
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The CNS is an immune-privileged organ, yet we know that peripheral immunity is critical for proper brain function. Here we will discuss cell communications in the meninges that regulate patrolling T cells and how the brain responds to T cell-derived signals.

OCTOBER 28 – IN PERSON AT RUDY NORTH LECTURE THEATRE 

  • Host: Dr. Catharine Winstanley
  • Speaker: Dr. Mihaela Iordanova, Concordia University
  • Title: Neurobiology of secondary fear triggers
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  • Meeting ID: 99412 188589
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The study of how the brain regulates learned fear has been fundamental to understanding brain function and has served as a pre-clinical animal model for fear- and anxiety-related disorders in humans. The current model has exclusively focused on primary triggers for fear, that is, fear acquired through direct pairings between a cue and a fear-eliciting event. However, fear is also elicited by secondary triggers, that is, cues that were never directly paired with the aversive event. These secondary triggers gain fear-eliciting properties by virtue of their association with primary triggers. The talk will present data showing how fear memories propagate across the memory network allowing for the development of secondary fear triggers, how those memories are regulated by fear to the primary triggers at the behavioural and neural level, as well as how they are supported by circuits in the brain.

NOVEMBER 4 – IN PERSON AT RUDY NORTH LECTURE THEATRE  

  • Host: Melanie Lysenko-Martin
  • Speaker: Dr. Ryan McLaughlin, Washington State University
  • Title: Lost in Translation: Leveraging Preclinical Models to Interrogate Effects of Developmental Cannabis Exposure
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Maternal cannabis use is a growing public health concern, yet the long-term effects of prenatal cannabis exposure remain elusive. Our understanding of how prenatal cannabis exposure affects the brain and behavior is critically informed by preclinical animal models that capture core components of human cannabis use. To this end, our laboratory and others have recently developed more translational models of cannabis use that have potential to provide unprecedented insight into the protracted effects of cannabis exposure during sensitive developmental stages.  In this presentation, I will describe recent data from our laboratory using a novel model of cannabis vapor self-administration in pregnant rat dams to investigate the long-term effects of maternal cannabis use on emotional reactivity, cognitive flexibility, and cannabis-seeking behavior. Additionally, I will present emerging data from our laboratory revealing altered excitatory inputs onto corticostriatal projection neurons in cannabis-exposed adult offspring, which could represent a mechanism by which prenatal cannabis exposure impacts reward-relevant behavior. Altogether, our data support the use of the cannabis vapor self-administration approach to investigate long-term effects of maternal cannabis use in developing offspring.

NOVEMBER 18 – IN PERSON AT RUDY NORTH LECTURE THEATRE 

Host: Dr. Lynn Raymond
Speakers:

  • Professor George Augustine –  Nanyang Technological University, Singapore
    Title: Synapses and synaptic circuits in health and disease
  • Professor Lim Kah Leong – Nanyang Technological University, Singapore
    Title: Neuroprotective and neurorestorative strategies for Parkinson’s disease
  • Professor Nagaendran Kandiah –  Nanyang Technological University, Singapore
    Title: Fluid biomarker and neuroimaging profile of mild cognitive impairment in Southeast Asians

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NOVEMBER 25 – IN PERSON AT RUDY NORTH LECTURE THEATRE 

  • Host: Jeff leDue
  • Speaker: Dr. Fabian Voigt, Harvard University
  • Title: Expanding the optical bag of tricks for neuroscience
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Seeing is believing and thus, optical imaging techniques are extremely useful to study brain structure and function. I will present two projects aimed at providing the neuroscience community with better imaging instrumentation. In the first part, I will introduce the mesoSPIM (http://mesospim.org/ ), an open-source light-sheet microscope that is optimized for fast imaging of large cleared tissue samples at 5-7 µm isotropic resolution. Since 2015, the mesoSPIM evolved from a crude prototype into a highly capable instrument and we built a global community around it. Currently, we are developing a benchtop mesoSPIM that is more compact and cost-efficient. In the second part, I will talk about a recent project that takes inspiration from scallops and astronomy to build novel multi-immersion microscope objectives that are well suited for imaging cleared samples. These objectives combine long working distances (>1 cm), large FOVs (>1 mm), high numerical aperture (currently up to 1.08) with diffraction-limited resolution in any homogeneous medium ranging from air to the typical high-index immersion liquids used for imaging cleared tissue. They are especially well suited to augment low-to-mid resolution mesoSPIM overviews with high-resolution datasets.

DECEMBER 2 – THE PRESENTATION HAS BEEN CANCELLED 

DECEMBER 9 – IN PERSON AT RUDY NORTH LECTURE THEATRE

  • Host: Dr. Lynn Raymond
  • Speaker: Dr. Michael Kobor, UBC
  • Title: Epigenetics and the Human Life Course
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Dr. Michael Kobor is a Professor in the Department of Medical Genetics at the University of British Columbia (UBC) and The Edwin S.H. Leong UBC Chair in Healthy Aging—a UBC President’s Excellence Chair. He began his academic studies in his native Germany, before coming to Canada to complete his PhD in Medical Genetics under Dr. Jack Greenblatt at the University of Toronto. He then completed postdoctoral training as a Human Frontier Science Program Fellow with Dr. Jasper Rine at the University of California, Berkeley. Dr. Kobor has received many distinctions, including a Tier 1 Canada Research Chair in Social Epigenetics, the Sunny Hill BC Leadership Chair in Child Development, and an appointment as Fellow of the Canadian Institute for Advanced Research (CIFAR) Child and Brain Development Program. A champion for translational research, he previously served as the Director for the “Healthy Starts” Theme at BC Children’s Hospital Research Institute. He also leads the UBC Social Exposome Research Cluster, an interdisciplinary effort spanning 8 Faculties that investigates the health effects of social and environmental factors and influences policies and interventions to reduce health disparities. Dr. Kobor is internationally recognized as a world-leader in the field of epigenetics and leads a program of research focused on illuminating the mechanisms by which environmental exposures and life experiences can “get under the skin” to persistently affect health and behaviour across the lifespan.

Objectives

  1. To learn about the importance and complexity of epigenetics across the human life course
  2. To understand the various ways by which the epigenome can inform on human health and disease
  3. To explore opportunities for collaborative research in human epigenetics and learn about the new Edwin S.H. Leong Healthy Aging Program at UBC

TERM 2 (WINTER 2023)

JANUARY 13

  • Host: Dr. Corree Laule
  • Speaker: Dr. Susan Gauthier, Weill Cornell Medical College
  • Title: Imaging a new treatment target in Multiple Sclerosis: Chronic Active Lesions
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  • Meeting ID: 91512 289258
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Innate immunity plays a pivotal role in the pathophysiology of multiple sclerosis (MS) and important cell types involved in this process are CNS resident monocytes (microglia) and blood-derived macrophages. Chronic CNS inflammation in the MS lesion is maintained, in part, with iron-laden pro-inflammatory microglia/macrophages (m/M) at the rim of chronic active MS lesions. These lesions are felt to contribute to a more aggressive phenotype of the disease; thus, represents a novel treatment target to reduce disease progression in MS. Identification of the subset of these lesions with a paramagnetic rim has been the focus of several in vivo studies evaluating the cross-sectional association of these lesions with disability, however further work is required to advance the development of this potential treatment biomarker. Utilizing quantitative susceptibility mapping (QSM) to measure chronic active lesions, our group has focused on generating tools to identify and quantify lesion-based chronic innate immune activity.  In this talk, I will review imaging approaches to identify chronic lesion-based inflammation and the impact of chronic active lesions on the disease course. I will further propose a novel application of QSM to quantify the inflammatory trajectory within chronic active lesions and provide a new treatment target in MS for current or novel immune modulators

JANUARY 20

  • Host: Dr. Kota Mizumoto
  • Speaker: Dr. Yuki Oka, California Institute of Technology
  • Title: Regulation of fluid homeostasis through gut-brain signaling
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Dr. Oka will discuss how innate instinct to consume water and salt is regulated through body-brain interactions.

JANUARY 27 – THIS TALK HAS BEEN CANCELLED 

FEBRUARY 3

  • Host: Dr. Shernaz Bamji
  • Speaker: Dr. Anastassia Voronova, University of Alberta
  • Title: (Re)generating oligodendrocytes in the developing and degenerating brain: a neural stem cell perspective
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Objectives:

1) Neural stem cells build and regenerate the brain in part by forming oligodendrocytes, the myelinating cells of the central nervous system

2) Endogenous neural stem cells can be engaged in mouse models of neurodegenerative disorders for brain remyelination

3) Neurodegenerative disorders may have a neurodevelopmental origin, and neurodevelopmental disorders may have a neurodegenerative component.

FEBRUARY 10 – THIS TALK HAS BEEN CANCELLED

FEBRUARY 17

  • Host: Dr. Lynn Raymond
  • Guest: Dr. Rosemary Bagot, McGill University
  • Title: At the intersection of threat and reward in nucleus accumbens glutamatergic afferents
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The nucleus accumbens integrates diverse inputs, balancing threat and reward to orchestrate motivated behaviour. Glutamatergic projections from the ventral hippocampus and medial prefrontal cortex converge in the accumbens medial shell and are implicated in reward processing as well as adaptation to chronic stress. How these pathways integrate aversive or appetitive events to modulate behaviour is not fully understood and largely unstudied in females, despite known sex-differences in stress-related psychopathologies. I will present new data using pathway-specific in vivo fibre-photometry and chemogenetic silencing to uncover how these projections encode aversive experiences to shape behavioural responding to threat and integrate information about the outcome of actions to shape learning about reward.

FEBRUARY 24

  • Host: Isabella Gallello
  • Guest: Dr. Joni Wallis, University of California, Berkeley
  • Title: Neuronal mechanisms of value-based decision-making: a brain-machine interface approach
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Decision-making is an unobservable cognitive process. This makes it challenging to investigate the underlying neuronal mechanisms. This lecture will discuss how techniques borrowed from the brain-machine interface field, such as decoding population activity and closed-loop control, can be used to understand how cognitive processes such as decision-making are implemented at the neuronal level. This approach could also lead to the development of novel devices for the treatment of neuropsychiatric disorders that involve impaired decision-making.

MARCH 3

  • Host: Dr. Catharine Winstanley
  • Title:  UBC Kickstart Updates
  • Speakers:
  • Dr. Annie Ciernia: Mechanisms of Peripheral Lipopolysaccharide Induced Brain Inflammation
  • Dr. Paul Van Donkelar: Characterizing tau pathology in survivors of intimate partner violence-related traumatic brain injury
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MARCH 10

  • Host: Dr. Catharine Winstanley
  • Title: UBC Kickstart Updates
  • Speakers:
  • Dr. Lynn Raymond/Neha Suvindran:  Rethinking Neuro-Bioelectronic Systems: Sustainable, Stable and Self-healing fibers
  • Dr. Rebecca Todd: Translational Investigation of Neurophysiological Substrates of Active and inhibitory Avoidance in healthy and depressed populations
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MARCH 17

  • Host: Dr. Jason Snyder
  • Speaker: Dr. Michael Drew, University of Texas at Austin
  • Title: Hippocampal mechanisms of fear suppression and relapse
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Learned fear often relapses after extinction, suggesting that extinction training generates a new memory that coexists with the original fear memory. Recent work from our lab has identified the hippocampus as a region where such fear and extinction memories exist and compete for expression. In this talk I will discuss recent work in our lab in which we have used activity-dependent neural tagging in mice to identify, manipulate, and characterize the cellular mechanisms of these hippocampal fear and extinction memories. I will discuss (1) where in the hippocampus these memory representations exist, (2) evidence that fear and extinction memories are coded by molecularly distinct cell ensembles, and (3) evidence that expression of fear and extinction is mediated by activation unique hippocampal output pathways.

MARCH 24

  • Host: Giulio Laino Chiavegatti
  • Speaker: Dr. Kathleen Morrison, West Virginia University
  • Title: Role for chromatin remodeling in the lifelong consequences of pubertal adversity on the brain and behavior
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Puberty and ensuing adolescence represent a time when the brain is rapidly developing and is sensitive to environmental stimuli. This lecture will discuss evidence that pubertal adversity puts females at risk for altered stress responding and maternal behavior later in life. Evidence will be presented that pubertal stress leads to an enduring programmatic event in the chromatin landscape in several brain regions, which may underlie both the lasting transcriptomic and behavioral consequences of pubertal stress.

MARCH 31

  • Host: Dr. Lynn Raymond
  • Speaker: Dr. Joseph Cheer, University of Maryland
  • Title: Endogenous cannabinoids and the pursuit of reward.
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In the early stages of substance abuse, subjects receive a drug that is highly reinforcing and are thus likely to repeat the actions that led them to obtain it.  This is termed positive reinforcement. However, in a minority of people who develop an addiction phenotype, negative reinforcement also causes a behavior to be repeated, but in this case, the action causes a bad feeling or situation to go away. The mesolimbic dopamine system, which is thought to generate a teaching signal, is involved in the selection of advantageous behavioral repertoires. This brain pathway is under control of endocannabinoid (eCBs), ubiquitous signaling molecules that bind to the same receptor targeted by marijuana (CB1) known to strengthen responses leading to the procurement of reward. Here, we investigate how eCBs modulate dopaminergic encoding of cues predicting either, appetitive stimuli, the avoidance of punishment or aversive outcomes. We find that disrupting eCB signaling by treating animals with a CB1 receptor antagonist dose-dependently decreased concentrations of dopamine release in the nucleus accumbens that were time-locked to a warning signal that predicts avoidance of punishment while simultaneously weakening shock avoidance behavior, effectively shifting the behavioral outcome from avoidance to escape. We further demonstrate, using directed mutagenesis approaches, that 2AG release from dopamine neurons in the midbrain is a canonical mechanism responsible for the pursuit of rewards.

It has been posited that compromised motivation in HD or “apathy” arises from a deficit in preparing for and initiating goal-directed behavior. Apathy is always the primary deficit in motivation associated with frontal-subcortical diseases such as HD. Indeed, apathy may be a core feature of HD disease pathology itself. In many cases apathy follows a similar trajectory as motor symptom progression in PD, although it can become prevalent before phenoconversion. It can be the result of several neurobiologically maladaptive systems, including affective (flattening of emotional responsiveness), behavioral (reduced initiation of spontaneous behavior), and executive dysfunction (difficulty planning/executing). Thus, motivational dysfunction in HD is a deficit primarily in preparation for motivated behavior that can have debilitating co-morbid consequences.

Gaps in knowledge

  • Loss of striatal cannabinoid type 1 (CB1) receptors is a key pathogenic of several neurodegenerative diseases, including HD.
  • Treatment for metabolic syndrome with the CB1 receptor antagonist Rimonabant was halted by the FDA because of loss of motivation and depressive ideation.
  • HD patients tend to smoke marijuana as a way to self-medicate and to prevent feelings of loneliness and helplessness.
  • Loss of goal-directed behavior in HD is specific to the incentive value of the reinforcer.
  • Treatment with indirect cannabinoid agonists profoundly increases operationally defined indices of motivation in normal animals and reverses apathy via dopaminergic mechanisms in mouse models of HD.

Together these data suggest that eCBs might modify distinct behavioral responses related to exteroceptive stimuli by modulating conditioned mesolimbic dopamine release events.  These findings suggest that therapies aimed at modifying tissue levels of eCBs may be used to prevent drug seeking driven by negative affective states or improve motivational indices in animal models of HD.

APRIL 14

  • Host: Dr. Stan Floresco
  • Speaker: Dr. Jared Young, University of California, San Diego
  • Title: TBD
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APRIL 21

  • Host: Dr. Mark Cembrowski
  • Speaker: Dr. Jesse Jackson, University of Alberta
  • Title: Examining the anatomy, physiology, and function of claustrum-cortical neurons.
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The claustrum is a small brain region forming dense synaptic connections with most of the cerebral cortex. However, the function of this region remains a mystery. I will highlight recent work from our group mapping the connectivity of claustrum neurons and determining how these cells control distinct cortical modules to participate in cognitive functions such as memory.

APRIL 28

  • Host: Dr. Mark Cembrowski
  • Speaker: Dr. Stuart Trenholm, McGill University
  • Title: A day in the life of a blind mouse
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It is well established that after vision loss, capabilities of the other sensory systems can be enhanced. However, particularly in animal models of vision loss, little has been done to examine how vision loss leads to alterations in the ‘blind brain’, and how these changes affect an animal’s behavior. Here I will discuss our recent work describing changes in neuronal activity and animal behaviour in mice following vision loss.

MAY 5

  • Host: Dr. Jacquie Quandt
  • Speaker: Dr. Yingxi Lin, Upstate Medical University, New York
  • Title: TBD
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MAY 12

  • Host: Dr. Doug Altshuler
  • Speaker: Dr. Christopher Pack, McGill University
  • Title: TBD
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MAY 26

  • Host: Dr. Annie Ciernia
  • Speaker: Dr. Kasia Bieszczad, Rutgers University
  • Title: TBD
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JUNE 2

  • Host: Dr. Kota Mizumoto
  • Speaker: Dr. Hokto Kazama, Riken Centre for Brain Science
  • Title: TBD
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JUNE 9

  • Host: Dr. Eric Accili
  • Speaker: Dr. Emily Liman, University of  Southern California
  • Title: TBD
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