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The Department of Biomedicine

BBB seminar: Emre Yaksi and Nathalie Jurisch-Yaksi

Studying the function and connectivity of neural networks in zebrafish brain

Emre Yaksi
Kavli Institute for Systems Neuroscience, NTNU, Trondheim

Our laboratory is interested in understanding how internal brain states, which are represented by the ongoing brain activity, interact with sensory information. For example, how does sensory world alter the way we feel, and how do our emotional states or learning affect the way we perceive the world. In order to answer some of these questions, we use a combination of two-photon calcium imaging, genetic tools and applied mathematics to study functional connectivity across zebrafish brain, especially in those circuits related to learning and emotional states. We observed patterned correlated activity across several interesting brain areas that are ancestral to mammalian habenula, amygdala, striatum, hippocampus and even prefrontal cortex. The functional/correlation-based brain maps that we generate using two photon calcium imaging data are robust across many animals, and resemble default mode networks observed in humans. Working in zebrafish, we also have the means to test the causality of such correlations in neural activity, by a combination of optogenetic stimulation and electrophysiological recordings of individual neurons. We find that a small brain nucleus, habenula, can integrate ongoing activity of multiple forebrain regions as well as sensory inputs.

We specifically focus our work in well-developed juvenile (3-4 weeks old) zebrafish. At this developmental stage zebrafish exhibit complex behaviors such as learning, social behaviors, anxiety etc. These complex behaviors are generated by a well-developed forebrain network which is comparable to mammalian telencephalon. While from zebrafish to humans, vertebrate brains evolve drastically, our data suggest that the ancestral forms of many mammalian cortical regions are present in zebrafish.

 

The function of motile cilia in ventricular flow and brain development

Nathalie Jurisch-Yaksi
Kavli Institute for Systems Neuroscience, NTNU, Trondheim

Coordinated beating of motile cilia leads to a directional fluid flow, which is important for various biological processes from respiration to reproduction. In the nervous system, motile ciliary beating of ependymal cells allows the cerebrospinal fluid (CSF) to flow through the ventricular system. Although motile cilia are not the only contributors to the CSF flow, their functioning is crucial, as human patients with motile cilia defects develop clinical features including hydrocephalus. Nevertheless, the role of motile ciliary beating in generating and organizing CSF flow and how CSF flow contributes to brain development and function remain elusive.

Here, we describe the mechanisms used by motile cilia to generate a specific flow pattern in the brain ventricles of zebrafish. Our results show that different populations of motile ciliated cells are spatially organized and generate a directional CSF flow powered by ciliary beating. We observe that cilia-driven flow is confined within individual cavities and there is surprisingly little exchange of fluid between ventricles. This compartmentalized CSF flow and its ventricular boundaries are abolished during bodily movement, thus highlighting the influence of external factors on the hydrodynamics of CSF flow. Finally, we demonstrate that aberrant CSF flow upon cilia ablation reduces hydrodynamic coupling between ventricles and disrupts ventricular development. Altogether, we propose that motile cilia-generated flow plays an important role in regulating the distribution of CSF within and across brain ventricles.


Chairperson: Boleslaw Srebro, Department of Biomedicine