Neural coding underlying odour concentration discrimination.

Animals relay on their sense of smell to locate food sources, mating partners and to avoid predators. To do this the brain measures how odour strength changes as the animal navigates in and out of an odour plume (chemotaxis). The brain must then inform the neurons that control movement about the direction of the odour gradient so that the animal makes the correct navigational choices to ensure that they reach the odour source or escape it. During chemotaixs, the fruit fly larvae can detect increases in odour concentration as they navigate an odour plume and this signals approach towards an odour source. A decrease in odour strength, on the other hand, instigates turning behavior and exploratory odour sampling in an attempt to correct navigation. Currently it is not known how the brain translated odour strength into controlled movement. The main reason for this is that the neurons involved in this process have not yet been identified. Therefore we still do not understand how sensory input drive chemotaxis behavior. We are using the fruit fly (Drosophila) larvae to identity the neural components that drive odour guided behavior. The Drosophila brain is smaller in terms of numbers of neurons than the vertebrate brain but the architecture of the neural systems that respond to odours share great similarities with more complex animals including humans. This simplicity makes it entirely feasible to identify the entire circuit involved in chemotaxis; a task that is difficult to achieve in the more complex vertebrate brain due to the increase in cell numbers and complexity.
We have come some way towards identifying the pathway underlying chemotaxis by characterizing a novel group of neurons (termed Odd neurons) that are an important link between odour sensing neurons and motor neurons that control movement. These neurons allow the animals to respond better to changes in odour concentration during navigation through an odour plume where odour concentrations are continuously changing. Our data suggest that the Odd neurons boost detection of odours to allow for better odour concentration discrimination. Importantly, our data also shows that the Odd neurons are not the only neurons involved in chemotaxis. Based on this we hypothesize that input from the Odd neurons onto a parallel pathway boosts the activity of this pathway allowing for better odour concentration discrimination during chemotaxis. The aim of this proposal is to test this hypothesis.
In order to do so we first have to identify the neural components of the parallel pathway. We know this pathway must be downstream to the Odd neurons which provides us with a unique opportunity to identify the neural pathway that control odour guided behaviour. We will use the Odd neurons as a starting point to identify the neural components of the parallel pathway that are immediately downstream of the Odd neurons. This will be achieved by mapping the Odd neurons onto a neural connectivity map generated in collaboration between a number of labs. This will provide us with the anatomy of the parallel pathway. To address our hypothesis we will then generate a toolkit that will allow us to characterize the activity of the neurons within the parallel pathway and manipulate their activity. The aim of this approach is to match the expression pattern of the genetic fly lines with the anatomy of the neurons identified above. Once we have obtained specific expression lines we can modulate the activity of Odd neurons and measure how changing the input from Odd neurons affect the activity of downstream neurons using genetically encoded calcium indicators. We can also use the expression lines to modulate the activity of downstream neurons to examine how this affect chemotaxis behaviour.

A fundamental goal of sensory neuroscience is to understand the neural circuits that extract relevant information from the environment and describe how sensory perception is linked to behavior. While we know a great deal about how odours are transduced into neural signals at the sensory periphery and how odour information is encoded at the first stages of sensory processing we know very little about the circuits that transfer information from higher olfactory processing centers to motor output circuits. I have identified a novel group of excitatory neurons, termed Odd neurons placed immediately downstream of higher olfactory processing centers in the larval Drosophila brain. We have shown using behavioural and imaging approaches that the Odd neurons play a crucial role during odour navigation (chemotaxis). The Odd neurons therefore provide us with a starting point that will allow us to identify the circuitry linking olfactory processing centres to chemotaxis behavior. Our data supports the hypothesis that Odd neurons improves odour concentration discrimination during chemotaxis by providing excitatory input onto a parallel pathway controlling odour navigation. This proposal aims to test this hypothesis. To address the hypothesis we will first characterize the direct post synaptic targets of the Odd neurons. Next we will generate the tools that will allow us to genetically target downstream components of the circuit. With these in hand we can test our hypothesis by analyzing neural responses in downstream neurons using functional imaging in combination with calcium sensors. We will manipulate the activity of Odd neurons to examine how input from Odd neurons modulate the activity of post-synaptic neurons. Finally we will test the behavioral relevance of functional connectivity by analyzing chemotaxis behavior. The findings from this proposal will lead to a better understanding of how odour stimuli are processed and transmitted within sensory circuits

This proposal will have an immediate impact on the scientific community and the research scientist that will be trained during the grant period. This proposal should also generate impact on the general public through teaching at both primary and secondary schools. More long term impact of the research could potentially be associated with heath.
Academic: Scientists across the neuroscience field would benefit from our research. These include scientist within the field of insect olfaction who can use our data to understand how olfactory stimuli are encoded and how innate behavior links to learning and memory. The cellular anatomy of the first stages of olfactory processing is remarkably well conserved between insects and vertebrates and findings from this proposal is therefore likely transferable to other organisms. Thus scientist working in the olfactory field in different species including humans would find our research informative. Neuroscientist in general will also be interested in our research since different sensory modalities and neural networks share common principles in neural coding. To ensure that our research is disseminated to as large an audience as possible I and the postdoctoral scientist will present data at national and international conferences in the form of talks or poster presentations. We will present our research at conferences that are specific to Drosophila as well as at meetings on sensory processing and general neuroscience. We will publish our research in peer-reviewed international journals and make available any tools and data sets generated during the research. Our research has the potential to elucidate how sensory stimuli drive behavior and the scientific community can build upon our research to understand how sensory processing in the brain can elicit different behavioral responses.
Training: The postdoctoral scientist requested will learn a wide range of techniques required to carry out research in Drosophila and will learn basic biological techniques that are applicable to different scientific fields. He/she will therefore have a good base knowledge of experimental approaches that will allow him/her to transition into other areas of research. If possible the post-doc will attend the Drosophila Neurobiology course: Genes, Circuits & Behavior. which is a 3 week course aimed at bringing the post doc up to date on the latest techniques used in Drosophila neurobiology In addition I will encourage the person to present data frequently which provides excellent opportunity to learn presentation skills and communication. These are important skills to acquire and are essential for a variety of careers outside science. The postdoctoral scientist will also receive training in different relevant computer software including imaging software which is used in many commercial jobs. In addition he/she will be taught to manage people and projects and these skills are directly transferable to a wide range of jobs.
Public engagement: I regularly engage with the public through teaching at both primary and secondary schools. I use my research to engage secondary school children in science and encourage them to pursue a career in science. My public engagement also includes teaching primary school children using my field of research to inspire the children to be inquisitive and seek methods to understanding how the world works. I will continue to engage in these activities throughout the grant period. I am also involved with organizations aimed at motivating women to return to the job market and these activities will also continue during the award period. The scientific techniques used in my research lend themselves particularly well to public demonstrations and I occasionally advice colleagues of how to implement chemotaxis assays at science events and demonstrations.