A goal of neuroscientists is to understand how the brain produces behaviour. The question of what is happening in the brain during behaviour is quite a brain-teaser. Neuroscientists' usual approach is to passively listen to brain activity in freely behaving animals. But what if we could actively excite a specific group of neurons in an animal's brain without using invasive electrodes? Lima and Miesenbock have developed a method to do just that; they have worked out how to stimulate a population of specific neurons in a fruit fly's brain by remote control.
To create their remote-controlled flies, Lima and Miesenbock genetically expressed phototriggers in particular cells in the central nervous system of the fruit fly, Drosophila. When they shone a light on these flies,the phototrigger-expressing cells were excited, i.e. they fired action potentials. In other words, the researchers could now stimulate a network of neurons in a freely behaving fly and observe the behavioural consequences,simply by illuminating the flies. To validate their method, the authors expressed the phototriggers in a very simple circuit that triggers a stereotypical behaviour with an all or nothing response. They chose the giant fibre system, which is responsible for a fly's typical escape manoeuvre: leg extension, jumping and wing flapping. They found that flies that had phototriggers expressed in giant fibre neurons exhibited these typical escape responses upon illumination. But when they illuminated flies that did not have phototriggers expressed in the giant fibre neurons, they saw that the flies didn't perform an escape response. Lima and Miesenbock also demonstrated quite dramatically that the visual system's response to illumination was not causing the escape response: they shone a light on decapitated flies and found that the headless flies still initiated an escape response.
Next, Lima and Miesenbock investigated the role of dopaminergic neurons in the control of movement. Dopaminergic function is important for planned movement, and a loss of dopaminergic neurons leads to a Parkinsonian syndrome of impaired movement. The authors wished to examine the behavioural consequence of an acute increase in dopaminergic signalling. To do this, they expressed the phototriggers in flies' dopaminergic neurons, illuminated the flies and watched the resulting flight patterns. Even though the flies' flight speed did not change after illumination, they were more active, because the number of pauses between flight episodes and the length of these pauses decreased. Before illumination, flies would fly along the edge of the container they were held in and rarely ventured through the centre. But when the researchers illuminated the flies, they saw that the insects began flying through the centre, often in crisscrossing or looped patterns. Clearly,stimulating flies' dopaminergic neurons triggers more complex flight patterns,perhaps by initiating more adventurous exploration of the central arena.
Identifying and stimulating functionally circumscribed but anatomically dispersed populations of neurons in moving animals has been difficult. Lima and Miesenbock's method might prove useful for the study of any behaviour that is controlled by a given circuit; i.e. most, if not all, behaviours. Courtship, mating, aggression, feeding, grooming, learning, sleep and wakefulness, and reward and punishment are just some potential contenders that the authors propose. Of course, this could also be a PhD supervisor's dream:they would only need to press a button to make their students jump!
