Integrative analysis of serotonin-mediated behavioural phase transition in the desert locust

Animals may undergo profound changes in their behaviour, body shape and colour in response to varying environmental conditions. This poses a major problem in biology: how do the surroundings in which an animal lives, influence the expression of its genes and mould its brain function, its hormones, and hence its behaviour, so that it is appropriately adapted to changing circumstances. The Desert Locust shows an extreme example of this malleability; it can change reversibly from a shy and inconspicuous, solitary creature that flies at night to one that is highly conspicuous, day flying and occasionally aggregates in vast numbers which has devastating economic effects. These two forms - the solitarious and gregarious phases - are strikingly different in appearance, physiology and behaviour. They can be bred in the laboratory and made to switch from one phase to the other and back, by simply raising them in isolation or in a crowd. They have relatively few nerve cells in their brain so that it is possible to understand the changes that occur during these phase transitions and to illuminate the similar mechanisms that occur in more complex animals when they find themselves in new circumstances. The key decision a locust must make is to join with or avoid other locusts. Once this has been made subsequent changes in physiology, body shape and colour follow from the continuing presence or absence of other locusts. Tickling the hind legs of a solitarious locust to mimic the effects of jostling with others, or the sight and smell of other locusts, can, in 1-2 h, cause the behaviour to become gregarious. This transition is accompanied by substantial changes in the amounts of many chemicals in its nervous system. In particular serotonin (a substance that in human brains affects many moods such as aggression and depression, and the release of which is affected by drugs such as ecstasy) shows a large but short-lived increase and, critically, it is both necessary and sufficient to induce the change in behaviour. We have determined which nerve cells show changes in their serotonin levels. We now wish to understand how serotonin changes the workings of nerve cells to bring about the transformation of behaviour. To achieve this aim we have these key objectives: 1. Identify and characterise the nerve cells that change their production of serotonin during the initial change in behaviour. How far do they extend through the central nervous system? How do they respond in the presence of other locusts, and what effects do they have on other nerve cells to bring about changes in behaviour? 2. Identify the nerve cells that are influenced by the release of serotonin. What chemical changes does serotonin cause in the internal workings of these nerve cells? This will be examined at the level of specific molecules that engage in cascades of chemical reactions to pass information within one cell and to neighbours. 3. Serotonin can change the effectiveness and the time course of communication between nerve cells, providing an essential building block of learning. How do differing amounts of serotonin in the nervous system before, during and after the experience of crowding, affect communication between nerve cells? Does serotonin have different effects in solitarious and gregarious locusts? 4. Examine in detail how solitarious and gregarious locusts differ in their patterns of daily activity such as feeding, exploring their environment and sleeping, and begin to look at how genes that regulate their body clock differ in the two phases. 5. Gregarious locusts quickly revert to solitarious behaviour if they are removed from the crowd. What are the mechanisms that maintain their gregarious behaviour and what is the complimentary process that leads to solitarious behaviour?

How does the interplay between the environment and gene expression mould brain function and behaviour so that an animal can adapt to changing circumstances? Desert Locusts show an extreme form of this phenotypic plasticity by changing from a shy animal, cryptic in appearance and avoiding other locusts, to one that lives in large groups, has bright warning colours as nymphs and is actively attracted to other locusts. We wish to capitalise on our recent breakthrough in identifying serotonin (5HT) as underlying the transformation from solitarious to gregarious behaviour, and our identification of neurons that up-regulate 5HT within 1 h of receiving gregarizing stimuli. We wish to build on these data by using a systems approach to identifying the sequence of processes, at molecular, cellular and neural levels that link the increased release of 5HT with changes of neuronal function and behaviour in this tractable model. We have these key objectives: 1. Characterise the anatomy and physiology of the individual serotonergic neurons that up-regulate 5HT production during behavioural gregarization. 2. Identify the targets of 5HT-mediated plasticity during phase change. We will determine: the targets of PKA phosphorylation both i) at the cellular level by identifying the anatomical location of neurons affected by gregarization and ii) at the molecular level, within neurons. 3. Determine how altered physiological function underlies the changes associated with behavioural gregarization. We will analyse how serotonin affects the physiology of identified neurons, before, during and after phase change. 4. Determine the behavioural consequences of phase change on circadian rhythms and aggregation. 5. Determine how the gregarious phase is maintained and how it is lost during the process of behavioural solitarization that occurs when gregarious locusts are isolated from the crowd.