Past events

Nature has created mechanisms to detect salient objects like food, prey or mates. Visual search is the process of shifting gaze from one salient object to another. It has both a stimulus driven bottom-up component as well as a task-driven top-down component. This is well studied in human and primates but not so much in other animals. It is, therefore, a challenge to increase our understanding of visual search in non-primate animals. The barn owl is a predator having frontally oriented eyes, but lacking eye movements. Because of such specializations, this bird offers itself for the study of visual search. We study mechanisms of visual search in this animal on both the behavioural and neurophysiological levels. In this talk I will present our main findings on these matters.

Displacement studies have clearly showed that birds are able to perform true navigation, i.e. they can find direction leading to destination from unfamiliar territory. Yet, the sensory mechanisms of navigation remain poorly understood. There are two primary hypotheses explaining the sensory nature of navigation: (1) a magnetic map hypothesis proposes that birds use parameters of the geomagnetic field which predictably distributed on the globe. This hypothesis claims that the magnetic receptor cells used for navigation reside in the upper beak (the so-called ‘beak organ’), and transmit information via the trigeminal nerve to the brain; (2) an olfactory map hypothesis assumes that birds can use olfaction and smell their position by taking advantage of odours predictably distributed in the atmosphere. In the last decade, I together with my co-workers have experimentally tested both hypotheses in migratory songbird species by combining sensory manipulations with displacements both in Europe and North America. Specifically, in our main model species, Eurasian reed warblers (Acrocephalus scirpaceus), a long-distance nocturnal migrant, we have found that this species (and maybe other songbird migrants) use geomagnetic cues and the magnetoreceptors embedded in the trigeminal system for geographical positioning. In parallel with our studies, there is a growing support for olfactory long-distance navigation in sea birds and homing pigeons. In my talk, I will overview the challenges of understanding true navigation in birds and present the most important advances in the context of other relevant studies.

cAMP dependent Protein kinase (PKA) plays a critical role in numerous neuronal functions including neuronal excitability, synaptic plasticity, learning and memory. Specificity in PKA signaling is achieved in part by the four functionally non-redundant regulatory (R) subunits. The inactive holoenzyme has a dimeric R subunit bound to two Catalytic (C) subunits. The full-length holoenzyme crystal structures allow me to understand how isoform-specific assembly can create distinct holoenzyme structures that each defines its allosteric regulation. High-resolution large-scale mosaic images provide global views of brain sections and allow identification of subcellular features. Analysis of multiple regions demonstrates that the R isoforms are concentrated within discrete regions and express unique and consistent patterns of subcellular localization. Using the miniSOG technique for correlating fluorescent microscopy with electron microscopy I find RIβ in the mitochondria within the cristae and the inner membrane, and in the nucleus, modifying the existing dogma of cAMP-PKA in the nucleus. Down-regulation of the nuclear RIβ, but not RIIβ, decreased L-LTP related signaling as reported by CREB phosphorylation in primary neuronal cultures, consistent with deficits observed in RIβ knockout mice. Furthermore, we show that a point mutation in the RIβ gene, that is associated with a neurodegenerative disease, abolishes dimerization while retaining robust interaction with the catalytic subunit. As a consequence, the interaction with an A-Kinase Anchoring Protein (AKAP) was also diminished. This mutation abolishes the AKAP-mediated targeting of RIβ holoenzymes to specific cellular compartments, which is consistent with an accumulation of RIβ in neuronal inclusions in patients carrying this mutation. These diverse interdisciplinary tools are defining PKA signaling as highly localized complexes that are targeted to specific sites in the cell in close to proximity to substrates and other signaling molecules where activity is then regulated by local levels of cAMP and calcium as well as kinases and phosphatases.

Neuronal plasticity is a unique property that describes the ability of the system to undergo long-lasting changes, typically as a result of experience. This paradigm, initially discovery by Bliss and Lomo and dubbed long term potentiation (LTP), describes a scenario where the post-synaptic responses increase in strength for long durations, following a particular pre-synaptic stimulus. Conversely, LT-Depression, describes the long lasting depression of synaptic responses. Today, these phenomena are commonly used to describe the molecular model for learning and memory. A large body of work has implicated more than a hundred proteins and factors in modulating LTP and LTD, and thereby memory. Unfortunately, there is still a lively debate regarding the true necessity and exact role of each player. The need for new techniques and approaches to further explore synaptic function and dysfunction has never been more pressing, as the number of people developing neurodegenerative diseases rises exponentially to epidemic scales, with the aging population. These diseases are characterized by a strong decline in the number of synapses and in the ability of synapses to undergo plasticity, ultimately resulting in the severe decline of cognitive function- such as learning and memory. To better scrutinize synaptic plasticity and probe the function and role of its initiators (i.e. NMDA receptors and calcium ions), I have developed novel light-gated NMDA receptors and photoactivatable fluorescent Ca2+-probes to monitor synaptic activity with unmet spatio-temporal resolution and reversibility. I use the latter to examine the roles of specific NMDA-receptor subunits in plasticity.

The vertebrate nervous system evolved a highly complex hierarchical architecture. While considerable progress has been made in describing the representation of behaviorally relevant state-variables by high-level circuits, how these circuits interact with low-level networks and modulate behavior is still poorly understood. In this talk I will describe two studies that begin to address this issue by exploring the transformations of motion representation across different tiers of the neural hierarchy. In the first study, conducted at Ehud Ahissar's lab at the Weizmann Institute of Science, we explored the generation and processing of rhythmic phase coding, previously reported as a key state-variable in cortical processing of rodent vibrissal perception. Using closed-loop motion control in anesthetized rats, we found that the vibrissal mechanoreceptors generate this invariant phase representation, which is then differentially processed by the various secondary brainstem populations. In the second study, underway in Leonard Maler's lab at the University of Ottawa, we focus on the preglomerular complex (PG) of the weakly electric fish Apteronotus leptorhynchus. This small, densely packed diencephalic structure serves as an exclusive gateway from the hindbrain and midbrain circuits to the telencephalon, which is involved in memory formation and spatial navigation. We found both spatial and temporal compression of motion related information conveyed through the PG bottleneck, suggesting an effective 'division of labor' between the low and high levels of the hierarchy.

Neuronal plasticity is a unique property that describes the ability of the system to undergo long-lasting changes, typically as a result of experience. This paradigm, initially discovery by Bliss and Lomo and dubbed long term potentiation (LTP), describes a scenario where the post-synaptic responses increase in strength for long durations, following a particular pre-synaptic stimulus. Conversely, LT-Depression, describes the long lasting depression of synaptic responses. Today, these phenomena are commonly used to describe the molecular model for learning and memory. A large body of work has implicated more than a hundred proteins and factors in modulating LTP and LTD, and thereby memory. Unfortunately, there is still a lively debate regarding the true necessity and exact role of each player. The need for new techniques and approaches to further explore synaptic function and dysfunction has never been more pressing, as the number of people developing neurodegenerative diseases rises exponentially to epidemic scales, with the aging population. These diseases are characterized by a strong decline in the number of synapses and in the ability of synapses to undergo plasticity, ultimately resulting in the severe decline of cognitive function- such as learning and memory. To better scrutinize synaptic plasticity and probe the function and role of its initiators (i.e. NMDA receptors and calcium ions), I have developed novel light-gated NMDA receptors and photoactivatable fluorescent Ca2+-probes to monitor synaptic activity with unmet spatio-temporal resolution and reversibility. I use the latter to examine the roles of specific NMDA-receptor subunits in plasticity.

microRNAs (miRNAs) are important post transcriptional regulators of the mRNA levels of key gene products in distinct cell types. The main focus of my PhD thesis was to mechanistically explore the emerging role of specific miRNAs in the complex regulation of the central stress response and to study their possible involvement in stress-induced psychiatric disorders. In this lecture, I will describe three related projects, demonstrating the identification and function of three stress-linked miRNAs and their involvement in stress response regulation and stress-induced psychopathologies in both preclinical models and human patients.

Mark Sagar is the director of the Laboratory for Animate Technologies at the Auckland Bioengineering Institute and a leading expert on creating interactive autonomously animated systems which will help defi the next generation of human-computer interaction and facial animation. He started his career building computer simulations of the human eye for virtual surgery, and later worked as the Special Projects Supervisor at Weta Digital and was involved with the creation of technology for the digital characters in blockbusters such as Avatar, King Kong, and Spiderman 2. His pioneering work in computer-generated faces was recognized with two consecutive Oscars at the 2010 and 2011 Sci-tech awards, a branch of the Academy Awards that recognizes movie science and technological achievements.