SEPTEMBER 9 – IN PERSON AT RUDY NORTH LECTURE THEATRE
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
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
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
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
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
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
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
Zoom option if unable to attend in person:
NOVEMBER 25 – IN PERSON AT RUDY NORTH LECTURE THEATRE
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
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.
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
Dr. Oka will discuss how innate instinct to consume water and salt is regulated through body-brain interactions.
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.
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.