Memory, motivation and individuality
Directed behaviour emerges from neural integration of sensory stimuli, memory of prior experience and internal states. The Waddell group seeks an understanding of these conserved neural mechanisms using genetically-encoded tools and the relatively small brain of Drosophila. By temporally controlling neural function memories can be implanted and internal states altered so that most flies behave according to our direction. Such recent studies have revealed a role for distinct subsets of dopaminergic neurons that innervate the mushroom bodies in reward learning, the control of motivated behaviour and the re-evaluation of learned information. The unique cellular resolution of the reinforcement system of the fly permits a detailed investigation of how it really works.
One might interpret the relative ease of altering behaviour to indicate that everything is simple in the fly brain. However, complexity arises in unexpected ways. Some transposable elements show cell-specific expression, including in long-term memory relevant neurons of the mushroom body. We have recently found that cell-specific expression arises from pieces of transposons being captured by splicing into cellular mRNAs. We are investigating how the additional transcript diversity contributes to gene expression, cellular and organismal individuality.
We are part of the Centre for Neural Circuits and Behaviour.
14th December 2020
Delighted the lab played a part of the truly landmark (and enormous) paper in eLife describing the complete neural network of the adult Drosophila mushroom body. So many amazing details and new clues to function. Lead author Feng Li (Janelia) and another output from our Wellcome funded connectomics collaboration with Greg Jefferis (Cambridge) and Gerry Rubin (Janelia). The connectome of the adult Drosophila mushroom body provides insights into function.
26th November 2020
Since my postdoc days at MIT, I've wondered about magnesium's reported memory-enhancing capacity. Exciting work from Yanying Wu now published in eLife shows that it's likely to be far more complicated that NMDA receptor blockade and receptor subunit compensation! Magnesium also improves fly memory and we find a Kenyon cell expressed Mg2+ efflux transporter to be critical for normal and Mg2+ enhanced memory. More to do but a very intriguing entree to the problem.
24th September 2020
So pleased to see Christoph Treiber's beautiful and important work published in Genome Research. The vast majority of transposon expression in the brain is actually pieces of transposons that are captured by splicing into cellular mRNAs. So transposon polymorphism produces a very different transcriptome in every fly. Transposon expression in the Drosophila brain is driven by neighboring genes and diversifies the neural transcriptome.
2nd July 2020
Amazing! Input connectivity provides solid evidence for heterogeneity of dopaminergic neuron function. Our first connectomics-driven paper in Current Biology headed by Nils Otto and in collaboration with labs of Greg Jefferis (Cambridge connectomics), David Bock and Gerry Rubin (Janelia). Input connectivity reveals additional heterogeneity of dopaminergic reinforcement in Drosophila.
13th April 2020
Incredible new paper from Pedro Jacob out in Neuron. Spaced training forms complementary long-term memories of opposite valence in Drosophila. Flies are smarter than people give them credit for. Turns out they explicitly learn which of the two odours is safe when trained using differential aversive spaced conditioning. Safety is coded by rewarding dopaminergic neurons and it's the safety memory that is protein synthesis-dependent LTM.
18th October 2019
Delighted with beautiful final outcome/output of Suewei Lin's postdoc project. His first graduate student Bhagyashree Senapati's work now published in Nature Neuroscience. A neural mechanism for deprivation state-specific expression of relevant memories in Drosophila.
18th October 2018
Exciting new paper from the lab in Cell. Integration of Parallel Opposing Memories Underlies Memory Extinction. Johannes Felsenberg does it again, this time helped by several others including Pedro Jacob and Nils Otto in Oxford. The first published output including data from our cool connectomics collaboration with Greg Jefferis, Davi Bock and Gerry Rubin.
19th April 2018
BOOM! First single-cell transcriptome study of the Drosophila midbrain from the dream-team Vincent Croset and Christoph Treiber in eLife. Cellular diversity in the Drosophila midbrain revealed by single-cell transcriptomics.
6th April 2018
Lab awarded an ERC Advanced Grant: Single-cell correlates of memory, motivation and individuality (aka SCCMI). Work that one out!
Interesting Press Attention
Christoph Treiber's work on transposon expression in the brain was 'featured' in the Daily Mail.
The lab was featured in an article by Philip Ball in The Guardian /Observer.
Suewei Lin's work on water reward and thirst was featured in an article in The New Yorker from Jonathan Weiner, author of Time, Love and Memory.