Transparent Zebrafish Shed Light on Brain Activity

Transparent Zebrafish Shed Light on Brain Activity

A fundamental question in neuroscience is how entire neural circuits generate behaviour and adapt it to changes in sensory feedback. Here we use two-photon calcium imaging to record the activity of large populations of neurons at the cellular level, throughout the brain of larval zebrafish expressing a genetically encoded calcium sensor, while the paralysed animals interact fictively with a virtual environment and rapidly adapt their motor output to changes in visual feedback. We decompose the network dynamics involved in adaptive locomotion into four types of neuronal response properties, and provide anatomical maps of the corresponding sites. A subset of these signals occurred during behavioural adjustments and are candidates for the functional elements that drive motor learning. Lesions to the inferior olive indicate a specific functional role for olivocerebellar circuitry in adaptive locomotion. This study enables the analysis of brain-wide dynamics at single-cell resolution during behaviour.

To date, measuring neuronal activity in a large region of nerve cells simultaneously has been a significant stumbling block to understanding the inner workings of the brain. In order to overcome this problem researchers at Harvard University and the University of Cambridge have developed a novel technique to measure the simultaneous activity of up to 2,000 neurons in zebrafish at the resolution of individual cells.

In order to perform their experiments the team modified the genetic configuration of transparent zebrafish, causing their neurons to fluoresce when active. Owing to the transparency of the zebrafish, the research team was able to image this fluorescent neuronal activity using a scanning electron microscope.

The experimental setup was used to test the hypothesis that zebrafish adapt their behavior in response to changes in their environment, the results of which have been published in the journal Nature. Dr. Misha Ahrens, one of the lead investigators on the study, explains:

“The paralyzed fish in the virtual world do indeed adapt their behaviour, by adjusting the amount of impulses the brain sends to the muscles. They also ‘remember’ this change for a while. Imaging the brain everywhere during this behaviour, we identified certain brain regions that were involved, most notably the cerebellum and related structures. This technique opens the possibility that eventually, the behaviour may be used to gain insights into human motor control and motor control deficits.”

While the zebrafish model is a simplified version of functioning of the human brain the researchers believe that the new technique will go a long way towards illuminating the inner workings of the human brain.

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