Sleep is a universal behavior that is present across the animal kingdom. We spend a third of our lives sleeping, disconnected from the world around us. Our sleep is closely regulated so that when we are sleep deprived, we ultimately compensate with longer, deeper sleep. Sleep helps our cognitive performance, promoting learning and memory consolidation. Lack of sleep immediately affects our cognition, mood, and health. All this suggests that sleep is essential, but what exactly is it about brain activity during sleep that is so crucial for restoring our normal cognition?
Sleep also involves dramatic changes to our perceptual awareness. Sometimes our consciousness fades altogether while at other times we experience vivid dreams. Although our brain continues to be active, we are mostly disconnected from sensory signals such as sounds, which would otherwise be perceived, trigger plasticity and result in behavior. How does the internal state of brain activity during sleep affect brain responsiveness and perceptual awareness?
Our goal is to understand how sleep relates to cognition and perception. Our research is guided by a belief that such studies require a combination of human and animal models. We therefore use multiple experimental techniques, focusing on the strengths of each setup to investigate the same key questions synergistically. Animal models are used to investigate underlying mechanisms, by performing detailed recordings of electrical activity and by manipulating neuronal activity with optogenetic, electrical and sensory stimulation. Human studies are carried out for careful investigation of cognitive factors and for studying large-scale brain activity (with fMRI, EEG, recordings in neurosurgical patients, and behavioral tests).
Main research projects currently in the lab:
- Study of the novel role of Kv2.1 potassium channel in insulin secretion from pancreatic islet β cells, as a target for novel drug design for the treatment of type-2 diabetes;
- Study of structure-function and modulations by presynaptic modulators of Kv2.1 and other Kv channels, specifically KCNQ2 and KCNQ3, important in axonal and synaptic excitability.
- Biophysical: 1) Two-electrode voltage clamp and patch clamp techniques for the study of whole cell and single channel currents. 2) Membrane capacitance and amperometry measurements for the study of exocytosis.
- Biochemical: co-immunoprecipitation, immunohystochemistry, recombinant protein purification, etc, for the study of in vivo and in vitro protein-protein interactions.
- Imaging: 1) Fluorescence Resonance Energy Transfer (FRET) for the study of protein-protein interactions. 2) Total Internal Reflection Fluorescence Microscopy (TIRFM) for the study of neurotransmitter vesicles behavior.
Behavioral and computational motor control is our field of research. This is a main venue for understanding the motor system and its organization, in healthy and clinical populations.
In the last years, we have dedicated major efforts in investigating methods and technologies (virtual reality, robot-based rehabilitation, neuro-stimulation) that can potentially enhance motor recovery and functional performance in clinical populations with a focus on upper-limb motion in stroke survivors.
Mathematical model-based, as well as empirical neuromotor approaches, are used in our research for studying and understanding laws of motor control and sensorimotor integration.
Investigating brain mechanisms underlie generation and regulation of the human emotional experience, in healthy and pathological states. The research is based on measuring indices of brain structure and functional dynamics via MRI (functional-MRI, DTI and Volumetric-MRI) and separate or simultaneous recording of electrical signals (scalp-EEG and intracranial-EEG).
The characterization of individual brain response is based on correlating neural activity and connectivity with behavioral and physiological measurements of emotionality (e.g. heart rate, hormone secretion, genetic expression, skin conductance, eye movements and verbal output). Induction of emotional states is achieved via film and music media, inter-personal interactions, and interactive social games. Regulation of emotions is modulated via on-line feedback protocols from brain signals in a closed loop set-up (i.e. NeuroFeedback).
The lab is also involved in studies aim to advance translation while focusing on neural markers of vulnerability and recovery with regard to post traumatic disorders (e.g. anxiety and depression), developmental disorders (e.g. schizophrenia and personality) and neurodegenerative disorders (e.g. Parkinson's Disease).
An essential part of this aspect of our work is the development of advanced new tools for acquiring and analyzing whole brain neural measurements; including applying multi-scale mapping for capturing dynamics of brain networks.
Projects in the lab include:
- Identification of the molecular determinants governing the activation of Ca2+-activated chloride channels.
- Elucidate the molecular rearrangements and architecture of membrane-embedded anion conductive Chloride Intracellular Channel (CLIC).
- Explore the functional expression and physiological importance of anion channels in resting and activated microglia
We study human movement in typical and clinical populations, with a focus on grasping and finger movements.
We are interested in fundamental questions such as how we learn to make new movements, how children develop motor skills during development, and how our motor function is affected by disorders such as stroke, dystonia or cerebral palsy. We also study the interconnection between decision making and human movements.
Our approach is to construct models that describe movement and force generation by the hand and arm, taking into account the biomechanics of the hand and the neural processes leading up to making movements. This approach gives us insights into the strategies behind the complex movements and force coordination required to successfully perform grasping and manipulation, as well as a greater understanding of the causes of differences in performance in individuals with motor disorders.
A goal of this research is to improve rehabilitation of hand function through improving our knowledge of these strategies.
Our research interests include investigations relating to tumor biology, tumor dormancy, mechanism of action of angiogenesis inhibitors, self-assembly of polymeric architectures and novel approaches to target cancer. Throughout, we have maintained an interest in understanding the biological rationale for the design of polymer therapeutics suitable for transfer into clinical testing.
Our primary interests are the molecular basis of tumor angiogenesis and the rational design of polymer therapeutics. Our research includes identification and characterization of genes and microRNAs associated with the switch from a dormant avascular tumor phenotype to a fast-growing angiogenic tumor in human cancers and their corresponding mouse models.
Research methods used include sequencing, gene cloning, quantitative RT-PCR, immunofluorescence, cell culture, scanning electron microscopy, mass spectrometry, MALS, AFM, NMR, HPLC, in situ hybridization, bioinformatics, polymer chemistry, molecular imaging, angiogenesis assays, animal models of cancer (human xenografts in mice, syngeneic and transgenic mice models), pharmacokinetics and pharmacodynamics and 3D printing.
The eye presents many challenges for research regarding unsolved conditions such as retinal and optic nerve assaults, damage to eye by surrounding conditions of work and every day activity.
The following specific subjects are studied:
- Optic nerve research: creating models of trauma and disease to investigate the mechanisms of degeneration and regeneration
- Investigate ways to treat corneal injury and diseases
- Ultraviolet light damage to the eye
- Research on the neovascular process in the eye and search ways to prevent it
- Occupational and environmental factors affecting eye and vision
|2012-2015||European Union FP7|
The research in the laboratory is focused on understanding the basic mechanisms underlying synaptic function and primary mechanisms initiating synaptic dysfunction at very early stages of Alzheimer’s Disease. To achieve this goal, we developed an integrated system that enables simultaneous real-time visualization of structural reorganization in spatially-restricted signaling complexes and functional modifications of single synapses in brain circuits.
Utilizing FRET spectroscopy, high-resolution optical imaging, electrophysiology, molecular biology, and biochemistry we explore experience-dependent mechanisms regulating the number and plasticity of hippocampal synapses under physiological and pathological conditions.
|2011-2016||Evolution of Alzheimer’s Disease: From Dynamics of Single Synapses to Memory Loss, European Research Council Starting Grant.|
Main projects in the lab include:
- Presynaptic monoamine transportes and the vesicular monoamine transporter as targets for neuropsychiatric drugs.
- Anxiolytic effects of new herbal treatment: mice models of anxiety and biochemical studies.
- Quaternary serotonin-reuptake inhibitors as novel anti-platelet drugs.
- Methylphenidate (Ritalin): abuse potential and long-term effects.
- Neuronal rescue by Rasagiline (MAO-B inhibitor) in thiamine deficiency.