How do memories become behaviour

We all have experienced the sudden recollection of what we perceived as long forgotten events or emotions triggered by an encounter with a particular image, smell or song. This is because each meaningful event that an animal experiences is stored in the brain as a memory but not all memories are retrievable in a manner that affects behaviour. Many memories are stored in a latent state and become behaviour only in particular circumstances. What determines whether a memory is expressed or remains latent is not well understood and maladaptation of this process in humans results in mental health problems such as Post-Traumatic Stress Disorder. Memories can be detected in two ways: as biophysical changes in the brain associated with a particular experience (so called 'engrams') and as behavioural actions (e.g. to avoid or approach a stimulus). Latent memories can be identified by the patterns in brain activity that a stimulus triggers despite this activity not being translated to behaviour. We have recently shown that the nematode Caenorhabditis elegans can store multiple memories associated to a common trigger at once, one negative in a latent state and one positive expressed as behaviour. Our findings provide the unique opportunity to elucidate the mechanisms by which memories compete for the control of behaviour in an animal that is highly amenable to genetic manipulation and has a small and anatomically well described nervous system. We hypothesize that there are specific neurons within each engram which drive behavioural expression (rather than storage). These neurons may be shared and regulated in opposite directions by engrams that are linked to a common trigger. To test this, we will: Complete the identification of the latent, negative engram. Identify the neurons within the negative and the positive engrams which drive behaviour. Identify signalling molecules through which the positive engram becomes behaviour. To carry out these aims, we will manipulate the activity of genes which we have identified to regulate the formation of the aversive engram and assess the impact on brain activity. We will carry out high-dimensional and quantitative analysis of behaviour to identify which specific parameters of movement are influenced by learning and map them to specific neurons. We will manipulate neuronal communication within the positive engram and assess the impact on brain activity and behaviour. Our findings will provide mechanistic insight into the long standing and fundamental question of how memories become behaviour. The project will deliver outcomes relevant to objectives set by the BBSRC and the government: the vision for life sciences to tackle main healthcare challenges; and the creation of a world class skilled workforce. A deeper and basic understanding of the processes underlying brain function, such as memory storage and expression, is fundamental for tackling mental health. The amenability of C. elegans to genetic manipulation provides a powerful platform for the discovery of molecules involved in memory processing which may become targets for innovation. The multidisciplinary nature of the project, which bridges classic systems neuroscience with molecular genetics and computational analysis, will provide the researchers involved with a broad set of skills transferable to many sectors of STEM. Training will go beyond research-based skills to leadership, communication and engagement. We will capitalise on how relatable learning and memory is to the general public and organise engagement events to communicate our work.