Not Bad is Good

Integration of parallel opposing memories underlies memory extinction

Learning not to be scared

Fear memories allow animals to predict and avoid possibly dangerous situations. However, if an expected threat does not happen, it is also important to learn to be less fearful. This re-learning process is called memory extinction. Although extinction has been postulated for many years to involve parallel memories, it is unclear how and where extinction memories are formed and how they compete with the original memory to neutralise learned fear.

In a recent study published in Cell Johannes Felsenberg and collaborators of the Waddell lab studied the neural mechanisms of extinction in the small brain of Drosophila. They discovered that extinction results from competition between two memories of opposing valence.

Flies can learn to avoid an odour that they experienced with unpleasant electric shock. However, if they are exposed to the odour again after training without shock, this reduces, or extinguishes, their learned avoidance behaviour.

Strikingly, extinction of aversive memory required dopamine-releasing neurons, some of which code for rewards, such as sugar. This suggests that flies perceive the absence of expected danger as something good.

Previous work from the Waddell lab established that good and bad odour memories are stored as changes in the efficiency of odour-specific input to different mushroom body output neurons. Looking for learning-induced changes at these locations in the fly brain allowed Pedro Jacob to see the co-existence of the original aversive memory, and a new extinction memory.

To understand how the two memories interact Amelia Edmondson-Stait, Markus Pleijzier and Nils Otto with collaborators in Cambridge and Janelia Research Campus traced the fine-structure of both neurons from a recently acquired electron microscope volume of the entire brain of the fly. Detailed reconstruction revealed that the two neurons housing the aversive and extinction memories are directly connected. The specific placement of inhibitory connections allows one neuron to gate information flow in the other. By directing his recordings to the processes downstream of the inhibitory synaptic connections, Pedro Jacob could see the two memories interact.

The full paper can be viewed here.

The work was featured in a Preview in Cell by Sheena Josselyn and Paul Frankland, Fear Extinction Requires Reward

Johannes Felsenberg, Pedro Jacob and Nils Otto discuss the work in a short film entitled Not Bad Is Good

A Fly Brain Atlas

Single-cell transcriptomes reveal cell-type diversity in the brain

A recent study published in eLife from Vincent Croset and Christoph Treiber in the Waddell group details the first single-cell level transcriptome of 10,286 cells that are representative of most of the cell-types in the midbrain of the fly.

The full paper can be viewed here.

Cellular diversity in the Drosophila midbrain revealed by single-cell transcriptomics

Scott Waddell awarded an ERC Advanced Grant

Professor Scott Waddell has been awarded an ERC Advanced Grant to study Single-cell Correlates of Memory, Motivation and Individuality. The proposal follows on the recent publication from the group (Croset, Treiber and Waddell, eLife 2018;7:e34550) detailing the first single-cell level transcriptome of 10,286 cells that are representative of most of the cell-types in the midbrain of the fly.

André Fiala

Abstract: 

Deciphering how neuronal brain circuits control behaviour represents a key task in modern neuroscience. A fundamental problem is to understand how brains integrate present sensory stimuli, past experience, and behavioural options. We aim at understanding how adaptive behaviour is organized through the properties of single neurons, their synapses, and the circuits the neurons are part of. A combination of genetic tools employing cell-specific transgene expression, e.g., opto- and thermogenetics, splitGFP reconstitution across cells, or functional optical imaging, advances the analysis of brains as integrated systems for the control of behaviour. For such an endeavour, the fruit fly Drosophila melanogaster is particularly suitable. It combines brain simplicity, behavioural richness, and experimental accessibility. We use associative olfactory conditioning paradigms to analyze how odour information is represented in the brain and how odour representations are associated with behavioural relevance through learning. As a model system of how a central brain structure brings about such adaptive behaviour, our research focuses on the mushroom body of the Drosophila central brain. The mushroom body of Drosophila is an evolutionary ancient third-order brain structure, comprising but ~2200 intrinsic neurons. It integrates input from multiple sensory modalities with experience-dependent modulation through multiple biogenic amines and neuropeptides. Its output then is integrated with innate behavioural tendencies to bring about adaptive behaviour. The mushroom body features structural, functional, or cellular similarity with several distinct mammalian brain structures. Our recent research on the function of the mushroom body will be summarized and discussed as a paradigmatic case of how a brain operates.

Biography:

Professor Fiala obtained his PhD in 1999 from the Free University of Berlin and was a research fellow at Memorial Sloan-Kettering Cancer Centre, New York. He was an investigator at the University of Würzburg between 2001-2008 and before becoming Professor of Molecular Neurobiology of Behaviour at the University of Göttingen. His laboratory uses Drosophila to study neuronal mechanisms underlying olfaction, learning and memory and goal-directed behaviour.

Resolving the prevalence of somatic transposition in Drosophila

Do transposons jump in the brain?

The shape and function of every cell in our body is determined by the amount and types of protein molecules that they produce. The building plan for each cell is stored in the DNA of the genome. This information is carefully copied and passed on to daughter cells during the reproduction, development and growth of all living organisms. Any changes (mutations) that occur in the DNA of each cell could potentially have devastating effects on the function of a cell. Surprisingly, a substantial portion of most animals’ DNA consists of so-called transposons, or ‘jumping genes’, many of which have ancient viral origin. These sections of the DNA have the potential to move or ‘jump’ into random locations throughout the DNA and they are therefore able to induce mutation. Previous studies have suggested that every single cell in our brains, and in some other parts of our body, might harbour several of these jumping genes that have moved to new locations in the DNA. However, detecting movement of jumping genes is difficult which has made this area of research controversial and hotly debated.

In a recent study published in eLife, Treiber and Waddell set out to map new locations of jumping genes in the DNA of cells in the brain of single fruit flies, hoping that lessons learned from these small insects would further understanding of jumping genes in the human brain. Changes to the DNA of cells in the fruit fly brain had previously been implicated in flies losing their memory when they age. If this is true, studying flies could even help explain how jumping genes might influence an animal’s behaviour.

Surprisingly, and maybe reassuringly, Treiber and Waddell found that jumping genes appear to be a lot less active than previously thought. But why had earlier studies reported high rates of gene jumping? It seems like the experimental process of preparing the DNA, where each single DNA molecule needs to be copied many times so that there is enough material to analyse, often wrongly joins together two bits of DNA that are normally not connected. When these joins occur close to a jumping gene they deceivingly make it look as if the gene has actually jumped. Treiber and Waddell found that many sites that people would previously have considered to be a new location of a jumping gene are actually just mistakes made when DNA fragments become incorrectly joined together when experimental samples are being prepared for analysis.

Treiber and Waddell also developed a new method that allowed them to quantify how often these artificial DNA joins occur in an experimental sample. Although this led them to conclude that gene jumping does not happen as frequently as previously thought it also provides the transposon research community with an important new tool that will hopefully help the development of new ways of detecting active jumping genes.

The full paper can be viewed here