Sleep and sleep disorders:
Sleep is an evolutionarily conserved process that is vital for animal survival. Sleep disturbances affect a large portion of the general population and represent a major health burden. Although sleep clearly improves brain performance, the function of sleep is unclear. We have characterized sleep, cloned sleep genes, visualized sleep circuits, and established zebrafish models for sleep disorders. We also found that sleep enable efficient nuclear maintenance of single neurons.
Neurodevelopmental disorders are characterized by cognitive, social, and motor deficits. The cause for these disorders is often genetic mutations that can lead to alteration in genetic pathways, neurogenesis, myelination, synaptic plasticity, and the activity of neural circuits. We established several zebrafish models for neurodevelopmental and endocrine disorders such as hypothyroidism, fragile-x-syndrome, narcolepsy and epilepsy. These models are used to identify and characterize the genetic, neural and behavioral mechanisms of the disorders, and to test potential genetic and pharmaceutical treatments.
Nerves, evolution and behavior in cnidarians:
We study the evolution and function of the nervous system in the ancient cnidarians (i.e. corals, jellyfish and sea anemone). We combine lab and field experiments, and use molecular and behavioral techniques to understand how a simple nerve net regulates behavior such as sleep.
Why do we sleep? Live imaging of the cellular mechanisms of sleep
Prolonged sleep deprivation can be lethal, and sleep disturbances are associated with various deficiencies in brain performance. However, how sleep affect the function of single neurons is unclear. We developed a technique to visualize single molecules in individual neurons of live awake and sleeping zebrafish. Using this approach, we found that sleep increases the movement of chromosomes (chromosome dynamics), which alters their structure to enable reduction of DNA damage, while neuronal activity has the opposite effect. Thus, chromosome dynamics can be a marker to define individual sleeping neurons, and one of the roles of sleep is to perform nuclear maintenance. The current research focus on nuclear and cellular mechanisms of sleep.
Sleep disorders and the hypothalamus
The hypothalamus regulates fundamental brain functions, such as reproduction, metabolism and sleep. The hypothalamic hypocretin/orexin (Hcrt) neurons are regulators of feeding, emotions, reward, sleep and wake, and Hcrt neuron deficiency results in the sleep disorder narcolepsy in humans and animal models. We established a transgenic zebrafish model, enabling inducible ablation of Hcrt neurons, as a model for narcolepsy. Using combination of RNA-seq, live-imaging, and behavioral experiments, we identify and characterize novel hypothalamic and Hcrt-neuron-specific genes in zebrafish. In addition, we study structural and functional connection between several neuropeptide-producing hypothalamic neuronal networks such as Hcrt, and neurotensin (Nts).
Sleep and synaptic plasticity
Sleep is conserved in evolution, and similar circadian and homeostatic factors regulate sleep in animals as distantly related as worms, flies, fish, and humans. Accumulating evidence shows that sleep is important for synaptic plasticity, memory, and learning. Using time-lapse two-photon imaging of excitatory and inhibitory pre- and post-synaptic markers, we study circadian and homeostatic control of rhythmic synaptic plasticity in the brain of live zebrafish.
Fragile X syndrome
Fragile-X syndrome (FXS) is the most common single-gene inherited neurodevelopmental disorder causing mental retardation. It is caused by mutations in the fragile X mental retardation 1 (fmr1) gene and the absence of the fragile X mental retardation protein (FMRP). The RNA-binding protein FMRP represses protein translation in synapses, and interacts with the adenosine deaminase acting on the RNA (ADAR) enzyme, which converts adenosine-to-inosine (A-to-I) and modifies the sequence of RNA transcripts. Utilizing the fmr1 zebrafish mutant (fmr1-/-), we study the link between ADAR-mediated RNA editing, neuronal circuit formation, and behavior in FXS.
The mechanism and treatments of thyroid hormone deficiencies
Thyroid hormones (THs; thyroxine/T4 and triiodothyronine/T3) are key regulators of embryonic development, metabolism, and neurogenesis in all vertebrates. Hypothyroidism is a common pathological condition that is characterized by insufficient activity of THs. In order to function, THs require specific transporter proteins that facilitate their uptake and efflux across the cell membrane, including the monocarboxylate transporter 8 (Mct8) and the organic anion-transporting polypeptide 1C1 (Oatp1c1). The X-linked psychomotor retardation Allan-Herndon-Dudley syndrome (AHDS) is associated with mutations in the TH monocarboxylate transporter 8 (mct8), and juvenile neurodegeneration is associated with mutation in oatp1c1. We utilize mutants (mct8-/- and oatp1c1-/-), thyroid gland-ablated and additional transgenic zebrafish to elucidate the neurological mechanism and find potential genetic and pharmacological treatments to these TH-related disorders.
Diving, Oxygen Toxicity and brain function
Exposure to high partial pressures of oxygen, which can occur during diving or hyperbaric chamber treatments, may lead to the development of a potentially fatal neurological condition - Central Nervous System Oxygen Toxicity (CNS-OT). CNS-OT is characterized by a loss of consciousness and the onset of seizures similar to tonic-clonic epilepsy. We use live imaging of transgenic zebrafish located inside a hyperbaric chamber, in order to understand the effect of oxygen toxicity on the brain in real time.
Sensory neuron. Red - Nueron Green(yellow) - Synapses (David Zada)
Hypocretin cell in Zebrafish head
Supervision of graduate and post-graduate students
David Zada, Post doc, 2019- present
Dana Sagi, PhD, 2019-present
Rotem Rozenblat Phd 2019-present
Daniel Forer MSc 2019-present
Talya Wasserma PhD 2018-present
Yuval Rave PhD 2018-present
Raphaël Aguillon, Post doc (CO-PI Prof. Oren Levy) 2019-Present
Shahaf Ben-Ezra MSc. (CO-PI Prof. Oren Levy) 2019-Present
Amir Harduf PhD.(CO-PI Prof. Oren Levy) 2020-Present
Adir Monsenego MSc 2018-2020
Dana Sagi, MSc, 2017-2019
Rotem Rozenblat MSc 2017-2019
Adi Shamay, PhD, 2014-2019
Tali Levitas, PhD, 2014-2019
David Zada,PhD, 2014-2019
Adi Tovin, Postdoctoral Fellow, 2012-2016
Arnon Itiel, MSc, 2013-2017
Idan Elbaz, PhD, 2012-2016
Laura Bekerman, PhD, 2010-2015
Gad Vatine, Postdoctoral, 2010-2012
Idan Elbaz, MSc, 2010-2012
Adi Shamay, MSc, 2012-2014
Tali Levitas, MSc, 2012-2014
David Zada, MSc, 2012-2014
Inbal Admati MSc, 2016-2018