Specific projects

​

Sleep disorders and the hypocretin/orexin (Hcrt) neuronal networks

​

The hypothalamus regulates fundamental brain functions, such as metabolism and sleep. Understanding the function of hypothalamic neuronal circuits is critical because of its association with neurodegenerative, genetic, sleep, and metabolic disorders. The hypothalamic 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 system-biology, genetics, live-imaging, and behavioral experiments, we identify and characterize novel 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.

 

Thyroid hormones and psychomotor retardation

​

Thyroid hormones (TH) are key regulators of embryonic development, metabolism, and neurogenesis in all vertebrates. The X-linked psychomotor retardation Allan-Herndon-Dudley syndrome (AHDS) is associated with mutations in the TH monocarboxylate transporter 8 (mct8). AHDS is characterized by severe intellectual deficiency, neuromuscular impairment, and high serum TH levels. We utilize mutant and transgenic zebrafish to elucidate the neurological mechanism and find potential genetic and pharmacological treatments to AHDS and other TH-related disorders.

​