Dynamic optical engine for investigation of neural activity in Drosophila melanogaster

How behavioural patterns arise from activity in neural circuits is a major question in neuroscience. Understanding this requires researchers to manipulate activity and the connections within a neural network and analyze how electrical impulses travel from one nerve cell to others, and behaviour is generated in a living animal. Electrical signals can in principle be implanted and detected in the brain using direct electrical connections formed by wires. However wire placement is not flexible, is highly invasive and is a particularly limited when working with an animal with a small brain, such as a fruit fly. Alternative light-based methods promise to overcome these limitations by permitting flexible remote stimulation and measurement of neural signals deep within the brain. Laser illumination can activate specific neurons and the resulting activity across a network can be read out using fluorescence microscopy. However, the effectiveness of optical methods is limited by the natural movements of the animals, the light distorting effects of brain tissue and the speed with which one can stimulate and image the neural activity. We will construct an 'optical engine' that will combine various optical methods to overcome these limitations and permit complex interventionist investigations of neural circuit function within the living brain.

We propose to develop a new tool combining several dynamic optical technologies into a single optical engine that will provide optical actuation and sensing methods to enable neuronal investigations in the living brain. The optical engine will incorporate active beam shaping for the three-dimensional control of photostimulation patterns, correction of aberrations caused by focussing through thick brain tissue, and active focal tracking and stabilisation to compensate for movements of the animal during observation. This will facilitate interrogation of complex neuronal interactions arising from the three-dimensional structure of the brain. We will initially optimise the engine for studies of the brain of the fruit fly, Drosophila melanogaster but it will be generally adaptable for investigation of brain function in vertebrates.

This proposal concerns the development of new technological tools that will enable neuroscience researchers to both pose and answer important questions about the structure of neural circuits. This research will lead to a better understanding of the causal relationships between neural activity and behaviour. Such scientific progress underpins advancements in medical science that will have benefits for health and quality of life. The introduction of the new tools into the research environment will have immediate benefit, as they will enable more complex investigation of brain function in a range of model animals than is currently possible. Technology developed in this project could potentially lead to commercial exploitation, bringing economic benefit.