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Simposio Internacional: Descifrando el desarrollo del cerebro: aproximaciones interdiscilinares hacia la comprensión y tratamiento de sus patologías International Symposium: Building up the brain: new interdisciplinary perspectives to understand and treat brain diseases Madrid, 15 y 16 de octubre de 2013 Madrid, October 15-16, 2013 RESÚMENES/ABSTRACTS v 1. A top-down systems biology approach to novel therapeutic strategies in Alzheimer´s disease, Patrick Aloy 2. Psychosis: the final pathway for an abnormal neurodevelopment, Celso Arango 3. Transcriptional control of cortex development, Suzana Atanasoski 4. Alzheimer´s disease pathogenesis: insights from neural development, Paola Bovolenta 5. Establishing bilateral brain wiring, Eloisa Herrera 6. Input-dependent controls over visual circuit assembly, Denis Jabaudon 7. Plasticity of specific inhibitory inputs in the visual cortex, Christiaan Levelt 8. Molecular Logic of Neocortical Projection Neuron Development and Diversity, Jeffrey D. Macklis 9. Cux transcription factors control plasticity to specify circuits in mammals, Marta Nieto 10. From wires to behavior: tools from computational neurobiology, Gonzalo de la Polavieja 11. LKB1 kinase as a master regulator of axon morphogenesis in mammalian: roles in axogenesis, axon branching and presynaptic function, Franck Polleux 12. Endogenous Hypercortisolism: a model for memory impairment, Eugenia Resmini 13. Unveiling network circuitry from spontaneous activity in neuronal cultures, Jordi Soriano Fradera 14. Genetic and post-mitotic control of area identity and cell-type specification in the developing mouse neocortex, Michèle Studer 15. Role of feedback signaling in neocortical development, Victor Tarabykin 16. Cellular mechanisms regulating patterns of converging inputs onto retinal neurons, Rachel O.L. Wong FUNDACIÓN RAMÓN ARECES Simposio Internacional: Descifrando el desarrollo del cerebro: aproximaciones interdiscilinares hacia la comprensión y tratamiento de sus patologías International Symposium: Building up the brain: new interdisciplinary perspectives to understand and treat brain diseases Madrid, 15 y 16 de octubre de 2013 Madrid, October 15-16, 2013 RESÚMENES/ABSTRACTS A top-down systems biology approach to novel therapeutic strategies in Alzheimer´s disease, Patrick Aloy High-throughput interaction discovery initiatives are providing thousands of novel protein interactions which are unveiling many unexpected links between apparently unrelated biological processes. In particular, analyses of the first draft human interactomes highlight a strong association between protein network connectivity and disease. Indeed, recent exciting studies have exploited the information contained within protein networks to disclose some of the molecular mechanisms underlying complex pathological processes. These findings suggest that both protein-protein interactions and the networks themselves could emerge as a new class of targetable entities, boosting the quest for novel therapeutic strategies. In this talk, I will summarize our work towards the characterization and modelling of the protein-interaction network underlying Alzheimer´s disease, together with our most recent attempts to decipher complex cell networks to the point of being able to predict how the perturbation of a node might affect the system as a whole. Volver/Return Psychosis: the final pathway for an abnormal neurodevelopment, Celso Arango Schizophrenia is a complex disorder caused by abnormal neurodevelopment with many different biological and psychosocial risk factors. The risk of having psychotic symptoms over a lifetime, as the persistence of those symptoms, the severity and disability they cause, and their recurrence over time depends on the interaction between genes and environmental factors. Environmental factors are more important the earlier they interfere with the normal neurodevelopment. That a brain with an abnormal neurodevelopmental trajectory ends up producing one symptomatology or another is a matter of the balance between risk and protective factors. Prevention of such severe mental disorders as schizophrenia syndrome through early interventions that act at the level of those risk factors is encouraging and augurs a promising future. As pluripotential stem cells can differentiate into different cell types depending on the environment, a given genotype can produce a brain with a higher or lower risk of developping dysfunctions such as psychosis, negative symptoms, or cognitive impairment depending on the environmental factors to which it is exposed. There are many FUNDACIÓN RAMÓN ARECES Simposio Internacional: Descifrando el desarrollo del cerebro: aproximaciones interdiscilinares hacia la comprensión y tratamiento de sus patologías International Symposium: Building up the brain: new interdisciplinary perspectives to understand and treat brain diseases Madrid, 15 y 16 de octubre de 2013 Madrid, October 15-16, 2013 RESÚMENES/ABSTRACTS pathways to what is called schizophrenia in the DSM-5 diagnostic criteria. Knowledge of those pathways will put an end to the use of the term schizophrenia and shed light on our current ignorance. Volver/Return Transcriptional control of cortex development, Suzana Atanasoski In the developing dorsal telencephalon, neural stem and progenitor cells generate a large variety of neurons with specific functions in the mature cortex. The proto-oncogene Ski is a transcriptional regulator linked to the human 1p36 deletion syndrome, which involves a set of phenotypes including brain abnormalities. Ski shows a dynamic expression pattern during cortical development, and accordingly, the phenotype of Ski-deficient cortices is complex, involving altered cell cycle characteristics of neural progenitors, disturbed timing of neurogenesis, and misspecification of projection neurons. Ski is likely to play a role in various pathways by its ability to interact with a range of signalling molecules, thereby modulating transcriptional activity of corresponding target genes. Cell-type specific interacting partners and downstream targets of Ski in cortical cells will be discussed. Volver/Return Alzheimer´s disease pathogenesis: insights from neural development, Paola Bovolenta The A Disintegrin And Metalloproteases (ADAMs) are a family of membrane proteases that cleave the extracellular domains of a variety of membrane bound proteins, releasing soluble peptides that modulate cell-to-cell communication or priming the substrate for further cleavage. Prominent examples of ADAM FUNDACIÓN RAMÓN ARECES Simposio Internacional: Descifrando el desarrollo del cerebro: aproximaciones interdiscilinares hacia la comprensión y tratamiento de sus patologías International Symposium: Building up the brain: new interdisciplinary perspectives to understand and treat brain diseases Madrid, 15 y 16 de octubre de 2013 Madrid, October 15-16, 2013 RESÚMENES/ABSTRACTS substrates are the Notch receptor, N-cadherin, L1, several cytokines and the amyloid precursor protein (APP). All these proteins control different events in CNS development and homeostasis, suggesting that ADAM activity must be tightly regulated to allow proper brain development and function. However, the identification of such regulators is just at the beginning. A recent example is Secreted Frizzled Related Protein1 (Sfrp1), which binds to and negatively regulates the proteinase activity ADAM10, a specific member of this family. As a consequence, genetic inactivation of Sfrp1 in mice increases Notch, N-Cadherin, L1 and APP processing. I will discuss the functional consequences of Sfrp1 inactivation in developmental events as well as in a mouse model of Alzheimer Disease (AD). I will discuss the relevance of these consequences in the possible treatment of AD. Volver/Return Establishing bilateral brain wiring, Eloisa Herrera Bilaterally symmetric organisms face the problem of how to integrate functions across the two sides of the body so that behavioral outputs can be properly coordinated. The importance of bilateral integration is especially evident in sensory perception such as binocular vision or in the control of movements. The integration of sensory inputs coming from both sides of the nervous system is possible thanks to the existence of commissural fibers that project from one side to the other during embryonic development. Axon midline crossing has revealed as a powerful model to investigate how growing axons are guided along specific pathways and, as a consequence, many of the main mechanisms that control this process are currently known. However, most axons in the CNS do not cross the midline but project ipsilaterally to transmit specific information into the same side of the brain. Work in our laboratory has recently revealed some of the main mechanisms controlling the cellular and molecular mechanisms underlying the formation of major ipsilaterally-projecting tracts in the CNS. Volver/Return FUNDACIÓN RAMÓN ARECES Simposio Internacional: Descifrando el desarrollo del cerebro: aproximaciones interdiscilinares hacia la comprensión y tratamiento de sus patologías International Symposium: Building up the brain: new interdisciplinary perspectives to understand and treat brain diseases Madrid, 15 y 16 de octubre de 2013 Madrid, October 15-16, 2013 RESÚMENES/ABSTRACTS Input-dependent controls over visual circuit assembly, Denis Jabaudon The molecular mechanisms that control distinct subtypes of neurons assemble to form input-specific circuits are poorly understood. Although input from the sensory periphery is required for modality-specific circuits to form, the cell-type specific mechanisms underlying these processes are largely unknown. Here, we investigate this question in retinogeniculate circuits, and examine the role of retinal input in the migration, differentiation, and synaptic integration of inhibitory interneurons in the visual thalamus. Using a combination of genetic, pharmacological, surgical and electrophysiological approaches in vivo and in vitro, we report that the targeted navigation and synaptic integration of dLGN within thalamic visual circuits is controlled by retinal input, providing an inputdependent control over thalamocortical neuron excitability. This reveals an inputdependent mechanism regulating circuit inhibition, which may account for the progressive recruitment of INs into expanding excitatory circuits during evolution. Volver/Return Plasticity of specific inhibitory inputs in the visual cortex, Christiaan Levelt The development of inhibitory innervation is an important factor determining the onset and closure of the critical period of ocular dominance plasticity in the visual cortex. The mechanisms through which inhibition regulates cortical plasticity and the types of interneurons involved are not well known. Using in vivo imaging techniques we provide evidence that structural plasticity of inhibitory synapses onto pyramidal neurons is a major component of plasticity in the neocortex. Post hoc immunohistochemical analyses show that this structural plasticity involves inputs from specific interneuron subsets. An optogenetic approach was used to address the functional implications of inhibitory synapse plasticity and which interneuron subsets it involves. We show that parvalbumin expressing interneurons are the main regulators of neuronal activity during the assessment of ocular dominance. Their influence on eye specific responses alters during ocular dominance plasticity and the functional implications will be discussed. Volver/Return FUNDACIÓN RAMÓN ARECES Simposio Internacional: Descifrando el desarrollo del cerebro: aproximaciones interdiscilinares hacia la comprensión y tratamiento de sus patologías International Symposium: Building up the brain: new interdisciplinary perspectives to understand and treat brain diseases Madrid, 15 y 16 de octubre de 2013 Madrid, October 15-16, 2013 RESÚMENES/ABSTRACTS Molecular Logic of Neocortical Projection Neuron Development and Diversity, Jeffrey D. Macklis Given the heterogeneity of CNS neuronal subtypes (of cerebral cortex / neocortical projection neurons in particular), and the complexity of their connections, detailed understanding of molecular controls over specification, differentiation, connectivity, and survival of specific neuronal subtypes and lineages will contribute not only to 1) understanding the development, organization, function, and evolution of CNS circuitry, but also to 2) identification of developmental and degenerative disease mechanisms and mono/polygenic vulnerability genes, to 3) support or regeneration of vulnerable populations in neurodegenerative (e.g. ALS, HSP/PLS, HD, PD) or acquired disease (e.g. SCI), to 4) enabling cellular models of neuron type-specific disease, and to 5) attempts to functionally repair CNS circuitry. For example, data from our lab and others demonstrate that new neurons can be added to adult neocortical and other CNS circuitry via manipulation of transplanted or endogenous progenitors in situ (including induction of limited neurogenesis of clinically important corticospinal motor neurons– CSMN– in adult mice), indicating that cellular repair of cortical and cortical output circuitry is possible, if controls over specific lineage differentiation are understood. Using FACS-purified CSMN and other neocortical projection neuron populations (including callosal projection neurons, corticothalamic projection neurons, cortico-brainstem projection neurons, corticostriatal projection neurons, and target-specific subsets of these populations) at critical stages of development in vivo, we have identified a set of multi-stage, combinatorially interacting developmental controls – both novel and largely uncharacterized transcriptional regulators and other genes, and cell-extrinsic controls – that are instructive for development of specific neuron subtypes as they develop in vivo (in particular, for CSMN, callosal, corticothalamic, and related projection neuron populations). These control key developmental processes from progenitor parcellation and progenitor subtype restriction, to subtype-specific differentiation, to acquisition of precise areal identity, to targetspecific axonal outgrowth. Loss- and gain-of-function analyses for multiple identified genes / molecules reveal a nested (~Boolean) “molecular logic” of progenitor-stage and post-mitotic, areally specific, combinatorial molecular controls over the precise development of key neocortical projection neuron populations. Some of these developmental controls are directly implicated or linked to human disease, and might both elucidate disease mechanisms and (polygenic) vulnerability, and enable directed control of neural progenitors (or ES / iPS cells) toward accurate disease models, neuronal support or regeneration, and functional CNS repair. Volver/Return FUNDACIÓN RAMÓN ARECES Simposio Internacional: Descifrando el desarrollo del cerebro: aproximaciones interdiscilinares hacia la comprensión y tratamiento de sus patologías International Symposium: Building up the brain: new interdisciplinary perspectives to understand and treat brain diseases Madrid, 15 y 16 de octubre de 2013 Madrid, October 15-16, 2013 RESÚMENES/ABSTRACTS Cux transcription factors control plasticity to specify circuits in mammals, Marta Nieto The development of precise intrahemispheric and interhemispheric connections is essential for the high order functions of the cerebral cortex. This balanced connectivity is affected in several human brain disorders, such as schizophrenia, epilepsy or autism. We focus our study on how Cux1 transcription factor determine the connectivity of cortical layer II-III neurons. Our recent work demonstrates that Cux1 regulates the excitability and plastical adaptative response of layer-II-III neurons during early postnatal development as a mechanisms to determine the f connectivity of the final circuit. Lack of plasticity as a result of Cux1 deficiency induces aberrant interhemispheric connectivity but does not affect local intrahemispheric circuits. I will discuss the cellular and molecular elements involved in this developmental mechanism, the consequences for the formation of the functional networks, and the implications for the understanding and treatment of mental disorders of developmental origin and other diseases of the nervous system. Volver/Return From wires to behavior: tools from computational neurobiology, Gonzalo de la Polavieja I will describe how tools from computational neurobiology can help us understand the structure and function of neuronal circuits. I will concentrate on three aspects: neuroanatomy, processing and behavior. For neuranatomy, I will show that the very simple idea of wiring economy can quantitative predict many neuroanatomical structures. Tools for the understanding of processing will be discussed for both single neurons and networks. Finally, I will discuss new tools for the analysis of social behavior, a particularly challenging type of behavior because it implies the complexities of interactions among animals. Volver/Return FUNDACIÓN RAMÓN ARECES Simposio Internacional: Descifrando el desarrollo del cerebro: aproximaciones interdiscilinares hacia la comprensión y tratamiento de sus patologías International Symposium: Building up the brain: new interdisciplinary perspectives to understand and treat brain diseases Madrid, 15 y 16 de octubre de 2013 Madrid, October 15-16, 2013 RESÚMENES/ABSTRACTS LKB1 kinase as a master regulator of axon morphogenesis in mammalian: roles in axogenesis, axon branching and presynaptic function, Franck Polleux The developmental mechanisms underlying axon morphogenesis of specific populations of mammalian neurons in vivo are still poorly understood at the cellular and molecular levels. Operationally, axon development can be divided in three major steps: (1) axon specification during neuronal polarization, (2) axon growth and guidance towards their final targets and (3) terminal axon branching and presynaptic development. A few years ago, we and others identified that the serine/threonine kinase LKB1 (also called Par4 and STK11) is required for axon specification in the developing cortex in vivo (Barnes et al Cell 2007). We recently discovered that at later time point, LKB1 is also required for axon branching in vivo. Interestingly, these two functions of LKB1 required two separate sets of downstream kinases (SAD-A/B kinases for axon specification vs. NUAK1 for axon branching). Furthermore, we demonstrated that LKB1NUAK1 kinase pathway regulate terminal axon branching by controlling mitochondrial capture at nascent presynaptic sites (Courchet, Lewis et al., Cell 2013). Some of the central unresolved questions raised by our recent results are: (1) what are the cellular and molecular mechanisms anchoring mitochondria presynaptically?, (2) how do presynaptic mitochondria regulate axon branching ? and (3) more generally what is the function of mitochondria once captured presynaptically? I will summarize these recently published results as well as some preliminary data demonstrating that, beyond being important for ATP production, presynaptic mitochondria play a critical role in calcium clearance through a unique calcium channel called the Mitochondrial Calcium Uniporter (MCU) which in turn plays a critical role in specifying presynaptic release properties in neurons. Interestingly, LKB1 seems to regulate axon branching through regulation of MCU abundance in mitochondria, affecting presynaptic accumulation during neurotransmitter release and presynaptic release properties. Volver/Return FUNDACIÓN RAMÓN ARECES Simposio Internacional: Descifrando el desarrollo del cerebro: aproximaciones interdiscilinares hacia la comprensión y tratamiento de sus patologías International Symposium: Building up the brain: new interdisciplinary perspectives to understand and treat brain diseases Madrid, 15 y 16 de octubre de 2013 Madrid, October 15-16, 2013 RESÚMENES/ABSTRACTS Endogenous Hypercortisolism: a model for memory impairment, Eugenia Resmini, Chronic exposure to endogenous hypercortisolism in Cushing’s syndrome (CS) is associated with negative effects on memory and hippocampal volumes (HV), even after biochemical cure. Hippocampus, which is critical for learning and memory, is rich in glucocorticoid (GC) receptors and is therefore particularly vulnerable to GC excess. With the advent of structural and functional neuroimaging techniques, the role of different nervous system structures and the hypothalamic-pituitary-adrenal axis can be investigated directly. HV have been calculated in CS patients using a 3tesla MRI and an automated procedure (Freesurfer) and compared to healthy subjects. Metabolites in the hippocampi of these CS patients have been also investigated with proton magnetic resonance spectroscopy (1H-MRS), a sensitive, non-invasive imaging technique capable of measuring brain metabolites in vivo. Concentrations of Glu (Glutamate), Glx (Glutamate+Glutamine), NAA (NAcetyl-aspartate), total-NAA (NAcetyl-aspartate+N-Acetyl-aspartyl-Glutamate), Cho (Glycerophosphocholine and Phosphocholine compounds), Cr (Creatine) and MI (mionositol) were measured (mmol/l). Verbal and visual memory performance has been evaluated. We hypothesized that in CS patients, impaired memory performances and decreased HV would be found, due to long term exposure to hypercortisolism. We found that CS patients had lower performances in verbal and visual memory tests compared with matched controls, but only those with severe memory impairments also had reduced HV. Brain atrophy and reduction in total and cortical gray matter volumes were observed in CS patients compared with controls, however subcortical gray matter reduction was seen only in those with severe memory impairment, in parallel to the findings of reduced HV. The negative effect of hypercortisolism on memory and HV was not totally reversible after biochemical cure. Moreover persistently abnormal metabolites have been demonstrated in the head of both hippocampi of CS patients, using 1H-MRS, despite endocrine cure of hypercortisolism. Low levels of NAA indicate neuronal dysfunction and/or loss, while high levels of Glx suggest concomitant glial proliferation, as a repair mechanism. These functional abnormalities could be considered early markers of GC neurotoxicity, would precede hippocampal volume reduction and could be implicated in the memory impairments evidenced in these patients. Whether less exposure to hypercortisolism by earlier diagnosis and successful treatment of CS would avoid the progression of memory problems and the reduction of HV remains to be confirmed. Volver/Return FUNDACIÓN RAMÓN ARECES Simposio Internacional: Descifrando el desarrollo del cerebro: aproximaciones interdiscilinares hacia la comprensión y tratamiento de sus patologías International Symposium: Building up the brain: new interdisciplinary perspectives to understand and treat brain diseases Madrid, 15 y 16 de octubre de 2013 Madrid, October 15-16, 2013 RESÚMENES/ABSTRACTS Unveiling network circuitry from spontaneous activity in neuronal cultures, Jordi Soriano Fradera Spontaneous activity (brain rhythms) plays a fundamental role in shaping neuronal circuits during embryonic development, while in the mature brain it is involved in tasks as important as motor coordination and memory. Despite the importance of spontaneous activity, the mechanisms that govern its initiation and maintenance are poorly understood. In this talk I will introduce neuronal cultures as a versatile experimental platform to investigate, on the one hand, the generation and richness of spontaneous activity patterns. On the other hand, I will introduce theoretical and numerical tools that help understanding the interplay between activity and connectivity in neuronal circuits. Finally, I will show how neuronal cultures, in combination with these multidisciplinary resources, provide a valuable platform to investigate dysfunctional neuronal circuits, for instance those associated with Alzheimer’s and Huntington’s disorders. Volver/Return Genetic and post-mitotic control of area identity and cell-type specification in the developing mouse neocortex, Michèle Studer Corticogenesis involves the formation of six distinct layers and of functionally specialized areas characterized by specific sets of pyramidal neurons with distinctive morphologies, connectivity, and gene expression profiles. Partitioning of the neocortex, also known as arealization, is thought to be decided at early stages by the expression of several patterning genes in neuronal progenitors. Recently, few post-mitotically expressed genes have been described to influence the correct specification and positioning of functional areas at later stages. However, whether post-mitotically expressed genes just refine and/or maintain area features imparted by progenitors or independently specify functional areas is still unclear. We have previously shown that the transcriptional regulator COUP-TFI, expressed in progenitors and newborn neurons, is required in balancing the neocortex into motor and sensory areas (1) by regulating a genetic program leading to the correct differentiation of deep layer projection neurons (2). In this study, we show by loss- and gain-of-function approaches that post- FUNDACIÓN RAMÓN ARECES Simposio Internacional: Descifrando el desarrollo del cerebro: aproximaciones interdiscilinares hacia la comprensión y tratamiento de sus patologías International Symposium: Building up the brain: new interdisciplinary perspectives to understand and treat brain diseases Madrid, 15 y 16 de octubre de 2013 Madrid, October 15-16, 2013 RESÚMENES/ABSTRACTS mitotic function of COUP-TFI is necessary and sufficient in imparting areal- and laminar-specific properties during corticogenesis. We also found that postmitotically expressed COUP-TFI exerts a negative feedback on the expression of mitotically genes promoting rostral identity. This envisages a crucial decisional function of COUP-TFI in post-mitotic cells during neocortical area and cell-type specification and reveals a high level of plasticity in setting up functional area properties during corticogenesis. 1) Armentano M., Chou S. J., Srubek Tomassy G., Leingärtner A., O’Leary D.D.M. and Studer M. COUP-TFI regulates the balance of cortical patterning between frontal/motor and sensory areas. Nature Neuroscience, 10, 2007, 12771286. 2) Tomassy Srubek G., De Leonibus E., Jabaudon D., Lodato S., Alfano C., Mele A., Macklis J.D. and Studer M. Area-specific temporal control of corticospinal motor neuron differentiation by COUP-TFI. PNAS, 2010, 107(8): 3576-81. Volver/Return Role of feedback signaling in neocortical development, Victor Tarabykin The neocortex is designated as the seat of our highest cognitive abilities. Comprised of functionally distinct neurons, the mammalian neocortex develops from progenitors lining the dorsal aspects of the lateral ventricles. The fate and position of these neurons is decided by the time they leave the germinal zone. However, little is known about how cortical progenitors learn how many neurons of each type to produce and when to make the switch from producing one neuronal type to the next. One source of instructions to the progenitors comes from the cortical plate itself, creating a feedback loop. Recently we identified Sip1 as a master regulator controlling the timing of corticogeneis. Sip1 is a transcriptional repressor, which interacts with the activated Smads, the transducers of TGF-ß signaling and with the NuRD complex. In my talk I will discuss molecular mechanisms down-stream of Sip1 that control the feedback. Volver/Return FUNDACIÓN RAMÓN ARECES Simposio Internacional: Descifrando el desarrollo del cerebro: aproximaciones interdiscilinares hacia la comprensión y tratamiento de sus patologías International Symposium: Building up the brain: new interdisciplinary perspectives to understand and treat brain diseases Madrid, 15 y 16 de octubre de 2013 Madrid, October 15-16, 2013 RESÚMENES/ABSTRACTS Cellular mechanisms regulating patterns of converging inputs onto retinal neurons, Rachel O.L. Wong Neurons must connect with the appropriate presynaptic cell types as well as establish a stereotypic number of synapses with each input type in order to perform their specific functions. To attain stereotyped connectivity patterns, developmental processes are in place to control the matching of synaptic partners, the relative convergence of distinct input types, and the number of connections formed by an individual axon onto a given postsynaptic cell. Indeed, many mechanisms that navigate axons and dendrites toward their synaptic partners are now known. However, what remain largely unidentified are the cellular interactions that regulate the number of synapses formed by each input type onto a common target cell. We have taken advantage of two wellcharacterized circuits in the vertebrate retina (mouse and zebrafish) to unravel the precise roles of activity-dependent and independent interactions that shape the connectivity of converging inputs. Perturbations to neurotransmission of specific presynaptic cell types in vivo enabled us to distinguish between cellautonomous and non-autonomous roles of activity. Targeted cell ablations in vivo helped unmask the importance of contact with presynaptic cells independent of their activity. Our findings in both systems underscore a key role for the dominant input in regulating the connectivity of other afferent types with the postsynaptic cell during development. A future direction is to better understand the capacity and mechanisms engaged to re-establish the wiring patterns of retinal circuits during regeneration and repair. Volver/Return *Todos los derechos de propiedad intelectual son del autor. Queda prohibida la reproducción total o parcial de la obra sin autorización expresa del autor. © FUNDACIÓN RAMÓN ARECES. Todos los derechos reservados. *All intellectual property rights belong to the author. Total or partial reproduction of the work without express permission of the author is forbidden. © FUNDACIÓN RAMÓN ARECES. All rights reserved. FUNDACIÓN RAMÓN ARECES