zebrafish spinal cord neurons, Erica Warp

Neurons in the spinal cord of a developing zebrafish
(from Warp, et al, 2012).

I am a neuroscientist by training and have focused my research on the development of the nervous system. I think it’s pretty amazing that we develop into a body made of trillions of cells, organized into tissues and organs, when we started just as a single fertilized cell. The development of the nervous system is particularly astounding to me, since it’s the most complex system in our body. Our brain is made of around 100 billion brain cells called neurons, each of which is of a particular type, expresses certain genes and wires to particular targets, together forming a biological computer with around 100 trillion connections or “synapses”. We don’t have enough genes in our genome to instruct the step-by-step building of this entire system and so the brain’s development is based on a combination of genetic instructions and experience-based responses. Our brain keeps developing throughout our whole life. Though our nervous system is VERY malleable when we are infants and children, it is still malleable into adulthood. Whenever you learn something new, there is a physical change in your brain. I guess I am a sucker for change.

During my PhD at the University of California, Berkeley in the lab of Ehud Isacoff, I studied the development of the zebrafish nervous system. Why zebrafish? Because they are transparent when they are young, so we are able to look right into them while they are developing and watch the whole process firsthand and in real-time. Using a fluorescent molecule called GCaMP that we can get particular cells to express, I watched how the first electrical activity in the developing nervous system starts, evolves, and responds to experience. Here you can see what the first electrical activity in the spinal cord looks like. It is quite random (each of those blobs lighting up is one cell!):

But after only a few hours (zebrafish develop FAST), this activity becomes very coordinated and looks like the type of activity that occurs during swimming (with left/right synchronization and alternation between the two sides):

I was curious if this early, uncoordinated activity was required for the later coordinated activity. In other words, are the locomotor-like patterns completely determined by genetics or do they require this earlier electrical experience? To test this, I used another light-based tool, this one called halorhodopsin, which stops the electrical activity of neurons when you shine yellow light on it. Using a microscope that had a way to target yellow light to the cells I was interested in and image the activity of these neurons at the same time, we were able to show that indeed the early activity is indeed important for setting up the later coordinated activity.

What is interesting is that all of this activity is what is called “spontaneous activity”. This is activity that is not triggered by the senses (which are not fully developed by this time), but is internally generated. It provides an important framework for the developing nervous system, and we see this type of spontaneous activity throughout all networks in the nervous system that scientists have stuck an electrode.

Warp E, Agarwal G, Wyart C, Friedmann D, Oldfield CS, Conner A, Del Bene F, Arrenberg AB, Baier H, Isacoff EY (2012) Emergence of patterned activity in the developing zebrafish spinal cord. Current Biology, 22(2):93-102. PDF Supplemental Information

Wyart C, Del Bene F, Warp E, Scott EK, Trauner D, Baier H, Isacoff EY (2009) Optogenetic dissection of a behavioural module in the vertebrate spinal cord. Nature, 461, 407-10.

Marriott G, Mao S, Sakata T, Ran J, Jackson DK, Petchprayoon C, Gomez TJ, Warp E, Tulyathan O, Aaron HL, Isacoff EY, Yan Y (2008) Optical lock-in detection imaging microscopy for contrast-enhanced imaging in living cells. Proc Natl Acad Sci, 105:17789-94.

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