CNC.IBILI

Neuroscience, Vision & Brain Diseases

The scope of the Neuroscience, Vision and Brain Diseases area is broad reaching, with more than 75 PhD-holding members conducting research in areas ranging from molecular and cellular mechanisms of behavior to human brain imaging of vision and high level cognition in health and disease. Researchers at CNC.IBILI are also at the forefront of translational research from molecule to man in visual, neurological and psychiatric diseases. These studies are linked to the design of intervention strategies to mitigate vision and brain diseases, including pharmacological and targeted genetic approaches to neurodegenerative and neuropsychiatric disorders. The translational nature of our research program is anchored on the notion that the aging population is under the burden of economic, societal and human challenge of mental disorders. Moreover developmental neuropsychiatric disorders such as Autism and Attention deficit hyperactivity disorder (ADHD) are being increasingly diagnosed. At CNC.IBILI we are particularly well positioned in this field, given the broad expertise of our internationally-competitive neuroscientists, at all levels of the basic and translational research chain.

Neuroscientists at the CNC.IBILI are focused on: 1) understanding central nervous system function at the cellular and molecular level, as well as the neuronal correlates of behavior, from vision to high level cognitive function, to support the translational research goal of 2) dissecting the mechanisms underlying neurodegenerative and neuropsychiatric disorders using established and in house newly-generated animal models of disease, biological human samples, as well as in vivo patient studies of disease mechanisms. The expectation is to understand basic mechanisms of retina and brain function in health and disease and to pinpoint dysfunction in pathological conditions leading to new treatment and prevention options. These studies address both fundamental question in basic molecular and systems neuroscience and key candidate mechanisms mediating vision and brain disease. We will foster transversal approaches that span analysis of brain function at the subcellular level, as well of neuronal ensembles and the whole brain.

The Neuroscience, Vision and Brain Diseases Thematic Strand is supported by 10 research groups, with extensive know-how in molecular and cellular neuroscience, in analyzing mechanisms of disease using animal models and a combination of biochemistry, electrophysiology and behavior analysis, as well as in human studies using cutting-edge brain imaging approaches. Additionally, successful genetic therapeutic approaches to neurodegeneration have been introduced. The groups are organized around central scientific questions, and bring together approaches at different levels. All groups have a solid track-record, are engaged in strong international collaborations with leader labs in their field, and have international visibility. There is a long-tradition of collaboration between the groups, and of cross fertilization between ideas and experimental approaches.

Research Groups

Neuro 1. Synapse Biology
Neuro 2. Redox Biology and Brain Sensing
Neuro 3. Neuroendocrinology and Aging
Neuro 4. Vision, Brain Imaging and Cognitive Neuroscience
Neuro 5. Purines in Brain Diseases
Neuro 6. Mitochondrial Dysfunction and Signalling in Neurodegeneration
Neuro 7. Aging and Brain Diseases: Advanced Diagnosis and Biomarkers
Neuro 8. New Targets and Therapeutics for Chronic Diseases
Metab 1. Cell Metabolism and Quality Control
Therapy 1. Vectors and Gene Therapy

Main Goals

The research groups address both fundamental questions about brain function and tackle the mechanisms of brain disease and strategies to resolve them, using animal models and human patients.

1. Synaptic Processes
Established know-how in molecular and cellular neuroscience, and in evaluating synaptic function/dysfunction is instrumental in addressing one of the overarching hypotheses of central nervous system diseases, which proposes an early role for synapse malfunction in disease etiology, both in neuropsychiatric and in neurodegenerative disorders. This flagship brings together groups working on synapse development and function, and on synaptic neuromodulation, as well as groups using animal disease models to detect or interfere with synaptic dysfunction, and groups testing hypotheses related to deficient neurotransmission involving the retina (a window to the brain), developmental and neuropsychiatric disorders. Key long-standing goals are to understand are 1) to understand the cellular mechanisms that govern synapse formation, function and plasticity; 2) to develop synaptic markers to evaluate synaptic function and dysfuntion in living animals and patients to confirm the validity of this hypothesis in an in vivo setting.

2. Brain Metabolism
The central nervous system is the major responsible for all body energy consumption and there is increasing recognition that limitations of energy supply to neuronal networks in terms of allocation of energy resources flexibly among regions according to neural demand is tightly associated with retina and brain dysfunction. The flagship fosters several inter-twinned goals, namely: 1) to probe if, how and where dysfunction of mitochondria (the main cell power plant) affects neuronal function and viability; 2) to grasp the determinants of neuronal and neurovascular coupling, the basis of imaging techniques in human patients; 3) to address the role of astrocytic and microglial metabolism in connection with neuronal activity, with the hope to understand neuronal metabolic dysfunction as well as to develop imaging markers for astrocytes to be used in human patients, given that humans have a 10 times greater astrocytic density than rodents.

3. Vision and Brain Imaging
Understanding visual and brain function and their impairment requires integrating the evaluation of molecular and phenotypic changes with state-of-the-art assessment of structure-function correlations in the central nervous system. This will be carried out by combining the evaluation of behavior in animal models and in patients with in vivo physiological recordings and imaging of the brain. Decision-making is an important feature of brain function, and comprises several levels, from simple perceptual decisions to goal-oriented behaviour under complex emotional and social contexts. We aim to elucidate the functional connectivity of core and extended neural architectures underlying choice behaviour, by combining unique multimodal approaches including MR techniques (spectroscopy, morphometry and function), molecular imaging (PET with 11C and 18F Chemistry), Transcraneal Magnetic Stimulation and large scale data integration. A translational research focus will be placed on the retina and visual pathways as neurophysiological biomarkers of brain function and dysfunction. A major goal is the elucidation of the pathogenesis and the identification of potential therapeutic targets in diseases that affect vision and brain function. Altogether these approaches provide the appropriate translation from in vitro and in vivo studies on therapeutic targets of diseases of the retina and the brain.