Past events

In the mammalian retina, visual information is transduced into electrical signals by photoreceptors. These signals are transmitted from photoreceptors to bipolar cells and on to ganglion cells, which inform the brain about contrast, form, color, object motion and other features of the visual world. On its route through the retina, visual information is modulated by inhibitory networks formed by horizontal and amacrine cells. Here, I focus on horizontal cells. At so-called triad synapses, these interneurons receive glutamatergic input from photoreceptors and provide feedback and feedforward signals to photoreceptors and bipolar cells, respectively. In recent years, we used different techniques to analyze the role of horizontal cells: we 1) deleted electrical synapses between horizontal cells, 2) ablated the entire horizontal cell population, and 3) selectively silenced horizontal cells by input deprivation. From these studies we gathered that horizontal cells are important for the spatial and temporal tuning of ganglion cells and are necessary to maintain the integrity of the first synapse in the visual system.

As signals progress along the early visual system, they undergo a remarkable transformation. One synapse away from the eye, in Lateral Geniculate Nucleus, responses are still highly repeatable, and they can be predicted fairly well by simple model of image processing. One further synapse away, in Primary Visual Cortex (V1), responses become hugely affected by activity that originates within the brain, which varies from trial to trial, and can be closely related to behavior. For instance, a major factor that controls responses of neurons in the mouse visual cortex is locomotion. In mouse V1, locomotion changes the nature of spatial integration, reducing the strength of lateral interactions. Moreover, locomotion interacts with vision to affect responses during navigation, perhaps to help the animal estimate is own movement. In the parietal visual areas that follow V1 a further factor affecting responses is decision. The activity of neurons in those areas thus reflects the interactions of vision, decision, and navigation. Current efforts in our laboratory are aimed at studying these interactions.

Gender differences affect the prevalence, presentation, treatment response and outcome of many neuropsychiatric disorders; including Alzheimer's disease, multiple sclerosis, depression and anxiety. However, despite a female majority among sufferers of these disorders, women were historically excluded from clinical trials; and the overwhelming majority preclinical studies on disease mechanisms and new drug development are conducted exclusively on males. Consequently, women are 50% more likely than men to experience adverse drug reactions, and between 1997 and 2001, 80% of the drugs removed from the market were specifically implicated in adverse side effects or deaths of female patients. Drawing on examples from diverse neuropathologies, the talk will describe the current status and the future potential of research and education on gender based medicine; aiming to level the field and gain insight into the influence of sex an gonadal hormones on CNS physiology and pathology.

The insulin-like growth factor-1 receptor (IGF-1R) signaling is a key regulator of lifespan, growth, and development. While reduced IGF-1R signaling delays aging and Alzheimer’s disease progression, whether and how it regulates information processing at central synapses remains elusive. Here, we show that presynaptic IGF-1Rs are basally active, regulating synaptic vesicle release and short-term plasticity in excitatory hippocampal neurons. Acute IGF-1R blockade or transient knockdown suppresses spike-evoked synaptic transmission and presynaptic cytosolic Ca2+ transients, while promoting spontaneous transmission and resting Ca2+ level. This dual effect on transmitter release is mediated by mitochondria that attenuate Ca2+ buffering in the absence of spikes and decrease ATP production during spiking activity. We conclude that the mitochondria, activated by IGF-1R signaling, constitute a critical regulator of information processing in hippocampal neurons by maintaining evoked-to-spontaneous transmission ratio, while constraining synaptic facilitation at high frequencies. Excessive IGF-1R tone may contribute to hippocampal hyperactivity associated with Alzheimer’s disease.

The ability to distinguish between individuals of the same species is the basis for all mammalian social relationships. This ability, termed social recognition memory (SRM), is mediated by a specific network of limbic areas in the brain, and is modulated by several neuromodulators, such as oxytocin and the CRH-related peptide urocortin-3. I will discuss behavioral and electrophysiological data suggesting a role for arousal-driven theta rhythmicity in this neural network during acquisition of social memory. I will also discuss the contributions of oxytocin and urocortin-3 to the social memory and the relationship between them. Finally, I will discuss a possible role for emotional states in cognitive processes such as learning and memory.

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.