Past events

The etiology of schizophrenia is complex and largely unknown, but consistent findings report a strong genetic component. While several potential schizophrenia-susceptibility genes have been identified, effect sizes are very small and replication is inconsistent, likely because of the complexity of human polymorphisms, genetic and clinical heterogeneity and the potential uncontrollable impact of gene-gene and gene-environment interactions. In this context, mutant mice bearing targeted mutations of schizophrenia-susceptibility genes are unique tools to elucidate the neurobiological basis of this devastating disorder. Using COMT*dysbindin-1 double mutant mice, we investigated the COMT*dysbindin-1 gene-gene interacting effects in the expression of rodents’ correlates of schizophrenia-relevant behavioral abnormalities. A major focus of our work is centered on how to dissect higher order cognitive functions in mice with high translational validity to human studies. In particular, in contrast to single genetic modifications, the combined decreased activity of both COMT and dysbindin-1 produced marked working memory, recency memory and attentional set-shifting deficits, and amphetamine supersensitivity; all abnormalities ascribed as mice’ correlates of schizophrenia-like symptoms. Based on this, we found evidence of the same non-linear genetic interaction in prefrontal cortical function in humans. Finally, to disentangle how COMT*dysbindin-1 interaction might converge in dopaminergic signaling, we measured in these double mutant mice dopamine levels in the PFC and dorsal striatum by in vivo microdialysis. Interestingly, concomitant COMT*dysbindin-1 reduction diminished dopamine levels in PFC and striatum, while amphetamine-evoked dopamine increase was attenuated in the PFC but exacerbated in the striatum. These findings illustrate a clinically relevant experimental animal model based on a predicted epistatic interaction of two schizophrenia-susceptibility genes and unravel interesting genetic mechanisms in the etiology of this mental illness.

I will discuss techniques that allow us to perform cellular and subcellular resolution imaging of neuronal activity in mice navigating in virtual reality environments and recent results from imaging place cells and grid cells. I will describe activity patterns that we have observed in hippocampal place cell dendrites and the implications for how associative Hebbian learning may take place during behavior. I will also describe the functional micro-organization of grid cells in the medial entorhinal cortex and what the organization might tell us about the circuits that generate grid cell firing patterns.

תקציר: התאבדות היא תופעה אנושית שחוצה תרבויות ותקופות הנחקרת במסגרת דיסציפלינות רבות ומגוונות. למרות המאמץ הרב-תחומי הענף לפענח את התופעה, היא נותרת במובנים רבים חידתית ונטולת הסבר מְספק. העיסוק בתופעת ההתאבדות נפוץ מאוד בעולם היצירה הספרותית, כביטוי נוסף לניסיון הבלתי נלאה לפענח ולמשמע את החריגה המתגלמת בהתאבדות מסדריו הנורמטיביים של הקיום האנושי. אקט ההתאבדות הוא כשלעצמו אתר של עימות בין כוחות סותרים רבי עוצמה, דהיינו דחף החיים אל מול יצר המוות, והוא עשוי להיקרא גם כבעל משמעויות עמוקות בכל הנוגע ליצר החיים המתבטא ביצירה האמנותית בכלל ובכתיבה בפרט. קריאת מעשה ההתאבדות הספרותית עשויה לשפוך אור על אתרים "אפלים" בנפש האדם ועל האופן שבו הספרות עשויה להעניק להם מילים ולפענח אותם. מחקרי מתחקה אחר ייצוגים של התאבדות במבחר יצירות בפרוזה מן הספרות העברית המודרנית תוך הפניית מבט סינכרוני ודיאכרוני אל ייצוגיה של התופעה בהקשרים הפסיכולוגיים, החברתיים והפוליטיים, וכן אל תפקידה התמטי והאסתטי בטקסט הספרותי. מטרתו של המחקר היא לבחון את מעשה ההתאבדות כפי שהוא מיוצג בספרות כנקודת מפגש עוצמתית ומיוחדת במינה בין כוחות מנוגדים חברתיים, פוליטיים ופסיכולוגיים. בהקשר הספציפי של הספרות העברית, שמתוכה נבחר קורפוס המחקר, ושעניינה המתמשך הינו התהליכים ההיסטוריים שעברה תנועת התחייה הלאומית מסוף המאה התשע-עשרה ועד היום, מצטרף דיון זה אל הניסיון המחקרי-תיאורטי הקיים לשרטט את יחסי הגומלין המשתנים בין הקולקטיבי לאינדיווידואלי בתרבות העברית המתחדשת.

Alexander Borst aims at understanding the foundations of information processing at the level of small neural circuits, focusing on the visual course control system in Drosophila. Borst’s lab uses a comprehensive approach , combining electron microscopy-aided anatomical reconstructions of the circuit, physiological characterization by both imaging and whole cell patch recordings, genetic circuit manipulation in behaving flies, computational modeling and last but not least, engineering of fly-inspired robots that implement the theoretical principles and test their functionality. Borst’s outstanding research has yielded a very precise and detailed description of the circuit at the single cell resolution as well as a thorough understanding of the computations it performs. Several of his major scientific contributions include the discovery that the direction of visually perceived motion is calculated following the Reichardt Model (Single & Borst, Science 1998), the separation of visual information in the fly brain into ON- and OFF-channels, similar to bipolar cells in the retina of vertebrate eyes (Jösch, Schnell, Raghu, Reiff & Borst, Nature 2010) and the existence of four types of neurons in each channel, tuned to one of the four cardinal directions (right, left, up, down) that project into four separate neuronal layers based on their preferred direction (Maisak et al, Nature 2013). https://www.neuro.mpg.de/borst

Alexander Borst aims at understanding the foundations of information processing at the level of small neural circuits, focusing on the visual course control system in Drosophila. Borst’s lab uses a comprehensive approach , combining electron microscopy-aided anatomical reconstructions of the circuit, physiological characterization by both imaging and whole cell patch recordings, genetic circuit manipulation in behaving flies, computational modeling and last but not least, engineering of fly-inspired robots that implement the theoretical principles and test their functionality. Borst’s outstanding research has yielded a very precise and detailed description of the circuit at the single cell resolution as well as a thorough understanding of the computations it performs. Several of his major scientific contributions include the discovery that the direction of visually perceived motion is calculated following the Reichardt Model (Single & Borst, Science 1998), the separation of visual information in the fly brain into ON- and OFF-channels, similar to bipolar cells in the retina of vertebrate eyes (Jösch, Schnell, Raghu, Reiff & Borst, Nature 2010) and the existence of four types of neurons in each channel, tuned to one of the four cardinal directions (right, left, up, down) that project into four separate neuronal layers based on their preferred direction (Maisak et al, Nature 2013). https://www.neuro.mpg.de/borst

Sensory stimuli in natural environments arise from many sources and the segregation of these sources into perceptually distinct objects is critical for an animal’s adaptive behavior. While segregation of visual and auditory signals has been studied extensively, little is known about the segregation of odors. I will describe our study aiming to provide a description of the behavioral ability of macrosmatic mammals to segregate odors. Specifically, we asked how the ability to segregate odors relates to features of the individual odors that are mixed. We developed a behavioral task for mice in which they were trained to report the presence of specific target odorants embedded in random background mixtures. We found that mice are highly capable of segregating an odor-figure from a background. Relating behavioral accuracy to the representations of target and background odors by olfactory receptor neurons, we found that the difficulty of segregation is not related to the similarity between odors, but rather is explained by the amount of overlap in the representations of background and target odors.

Abstract: Arm amputation provides a powerful model for studying plasticity, as it results in massive input and output loss consequential to losing a hand. Amputation also leads to profound changes in behaviour, driven by individuals’ need to compensate for severe disability (adaptive behaviour). Despite this strong behavioural pressure, research on amputation has been largely restricted to deprivation-driven (and supposedly passive) brain reorganisation, with little regard for the potential interaction between deprivation and behavioural related plasticity. As a consequence, sensory deprivation is widely held to cause maladaptive plasticity, resulting in phantom pain. Using a range of neuroimaging approaches I examine the extent to which experience modulates brain structure and function in amputees and individuals with congenital hand absence. I present evidence to challenge the proposed link between cortical reorganisation and phantom pain, and instead demonstrate preservation of topographic representations of the missing (‘phantom’) hand. I will show that phantom pain is associated with maintained representation of the phantom hand as opposed to brain plasticity, with potential implications on future treatment. Instead I provide new evidence that adaptive behaviour leads to extensive reorganisation, such that the limb engaging in compensation for disability takes over the cortical territory of the missing hand. In amputees, this process of adaptive plasticity occurs well beyond the traditionally conceptualised “critical period”. Finally, I provide new evidence for the relationship between lateralised limb-use patterns and lateralised structural and functional organisation in the resting brain. Based on this evidence, I suggest that plasticity in amputees is experience-dependant, and is not inherently maladaptive.