Scott Waddell, Ph.D.

Academic Role: Associate Professor

Faculty Appointment(s) In:
   Neurobiology

Other Affiliation(s):
   Interdisciplinary Graduate Program
   Program in Neuroscience

Drosophila Olfactory Memory

Studies over the last century have determined that memory exists in time-dependent phases and is converted from a labile to a stable state after training by a process termed consolidation. In mammals memory consolidation involves both parallel and sequential use of distinct brain regions. Consolidation initially requires the neural circuitry of the hippocampus and cortex but once the memory is consolidated, the requirement of the hippocampus is diminished. Hippocampal damage impairs the consolidation of new memories but leaves old memories intact suggesting that consolidated memories permanently reside in the cortex.

Using olfactory memory in the fruit fly Drosophila as a model, we are studying how memory is encoded and stabilized at the molecular, cellular and neural network level. Our work has established that the simpler fruit fly brain also employs parallel and sequential use of different regions to process memory.

Flies are taught to discriminate between odors following odor pairing with an electric shock punishment or with a sugar reward. Trained flies learn to either run away, or run toward, the appropriate odor. The reduced complexity of the fly brain (approx 250,000 neurons) and the fantastic genetic tool-kit make the study of memory in the fly readily accessible to precise interventionist analysis. Using the most up to date approaches, our work has established that distinct regions of the fly brain are involved at different times to process memory (Figure 1). Mushroom Body a´b´ neuron activity is required to form memory, Mushroom Body a´b´ neurons and Dorsal Paired Medial (DPM) neurons are transiently required to consolidate memory and output from Mushroom Body ab neurons is exclusively required to retrieve memory. We interpret these results to suggest that odor memories are formed in ab neurons, and are stabilized there by recurrent activity involving a´b´, DPM neurons and the ab neurons themselves. We therefore have broken down some of the memory-relevant brain circuits into discrete, but interacting, functional units and even down to the resolution of two neurons (DPM neurons). This work is likely to illuminate principles of neural circuit organization and function.

In addition, many conserved cell-signaling cascades have been implicated in fly memory and we aim to understand the neural circuit context in which these pathways are employed to encode memory.

Figures

Figure 1. Memory-relevant neurons revealed by enhancer trap-driven expression of Green Fluorescent Protein. c305a specifically labels Mushroom Body a´b´ neurons and c739 specifically labels ab neurons. DPM neurons can be visualized and manipulated using c316.

Figure 2. Model for aversive olfactory conditioning and DPM neuron-dependent memory processing. a | Training. Odour input through projection neurons (PN) activates a sparse parallel array (red) of mushroom body Kenyon cells (KC) that project in the α′β′ (light blue) and αβ (pink) lobes. The reinforcing effect of punitive shock is delivered to the mushroom body by dopaminergic modulatory neurons (DA, orange). Activated synapses are coloured yellow. The encoded memory gains specificity through its reliance on coincident DA release onto Kenyon cells that have been activated by odour. Therefore, although DA is released onto all Kenyon cells, synaptic plasticity is only induced at the output synapses (blue circles) of the red neurons. b | Short-term memory (STM) retrieval. Re-exposure to the conditioned odour activates the learning-modified red Kenyon cells. Output through the modified Kenyon cell α′β′ and αβ output synapses (blue circles) leads to an aversive conditioned response.  Plasticity was also induced at the α′β′ Kenyon cell–dorsal paired medial (DPM) neuron synapse, but transmission through this synapse is not required for short-term memory. c | Memory consolidation. Spontaneous activity (open blue triangle) in the projection neurons after training occasionally drives the red α′β′and αβ Kenyon cell neurons. Activity in the red α′β′neurons strongly drives DPM neurons (green) through the modified α′β′ Kenyon cell–DPM synapse. DPM neurons feedback onto all α′β′ and forward onto all αβ Kenyon cells. Although DPM neurons release transmitter on all Kenyon cells, consolidation is neuron specific because it is reliant on the cells’ history (that is, only the red neuron synapses that were modified during training can be consolidated) and coincident red Kenyon cell and DPM neuron activity after training. Each time the red Kenyon cells are spontaneously activated over the next hour, the recurrent α′β′ Kenyon cell–DPM neuron loop consolidates the output synapses in the red αβ Kenyon cell neurons (larger blue circle), while plasticity in the red α′β′ neuron output synapses (blue/red circle) wanes. d | Middle-term memory (MTM) retrieval. Re-exposure to the conditioned odour activates the red Kenyon cell neurons. However, only transmission from the consolidated αβ Kenyon cell output synapses (larger blue circle) is required to elicit the aversive conditioned response.

Representative Publications

DasGupta S, & Waddell S. (2008). Learned odor discrimination in Drosophila without combinatorial odor maps in the antennal lobe. Curr Biol. 18:1668-74.

Krashes, M. J. & Waddell, S. (2008). Rapid consolidation to a radish and protein synthesis-dependent long-term memory after single-session appetitive olfactory conditioning in Drosophila. J Neurosci. 28: 3103-13.

Keene, A. C. & Waddell, S. (2007). Drosophila olfactory memory: single genes to complex neural circuits. Nat Rev Neurosci. 8: 341-54.

Krashes, M. J.*, Keene, A. C.*, Leung, B., Armstrong, J. D., Waddell, S. (2007). Sequential use of mushroom body neuron subsets during Drosophila odor memory processing. Neuron 53: 103-112.

Keene, A. C.*, Krashes, M. J.*, Leung, B., Bernard, J. A., Waddell, S. Drosophila dorsal paired medial neurons provide a general mechanism for memory consolidation. (2006). Current Biology 16:1524-1530.

Yu, D., Keene, A. C., Srivatsan, A., Waddell, S., Davis, R. L. (2005). Drosophila DPM neurons form a delayed and branch-specific memory trace after olfactory classical conditioning. Cell 123: 945-957.

Keene, A. C. & Waddell, S. (2005). Drosophila Memory: Dopamine signals punishment? Current Biology  15: R88-90.

Waddell, S. (2005). Courtship Learning: Scent of a Woman. Current Biology 15: R88-90.

Keene, A. C., Stratmann, M., Keller, A., Perrat, P.N., Vosshall, L.B., Waddell, S. (2004) Diverse Odor-conditioned Memories Require Uniquely Timed Dorsal Paired Medial Neuron Output. Neuron 44: 521-533.

Leung, B. & Waddell, S. (2004). Four-dimensional gene expression control: Memories on the fly. Trends in Neurosciences   27: 511-513.

Waddell, S. (2003). Protein phosphatase 1 and memory: practice makes PP1 imperfect? Trends in Neurosciences 26: 117-119.

Waddell, S. (2002). Forgetting those painful moments. Neuron 35: 815-817.

Waddell, S. & Quinn, W. G. (2001). What can we teach Drosophila? What can they teach us? Trends in Genetics 17: 719-726.

Waddell, S. & Quinn, W. G. (2001). Fas-Acting memory. Developmental Cell 1: 8-9.

Waddell, S. & Quinn, W.G. (2001) Flies, Genes & Learning. Ann. Rev. Neuroscience 26:1283-1309.

Waddell, S., Armstrong, J.D., Kitamoto, T., Kaiser, K., Quinn, W.G. (2000). The amnesiac gene product is expressed in two neurons in the Drosophila brain that are critical for memory. Cell 103: 805-813.

Potential Rotation Projects

The Waddell lab explores learning and memory at the molecular, cellular and neural circuit level using the power of genetics in Drosophila. Ongoing projects evolve quickly and this web-page is always far behind.

Our field is wide-open and there are many experimental avenues to pursue. These projects are available for rotation students and the eventual choice is somewhat determined by student enthusiasm. I therefore encourage potential students to contact the lab, and meet the people, to determine their respective interests.

We are a lively bunch on the 7th floor of the LRB. The Waddell lab currently has two postdocs and three students. Students can expect to gain a broad expertise including molecular biology, genetics, imaging and behavioral analysis using Drosophila as a model.

Laboratory Personnel:

Graduate Students

Shamik DasGupta

Michael J. Krashes

Paola N. Perrat

Postdoctoral Fellows

Benjamin Leung

Jena L. Pitman

Academic Background

Scott Waddell received his B. Sc. (1991) from the Department of Biochemistry at the University of Dundee and his Ph.D. (1996) from the University of London, U.K. He received a Wellcome International Prize Traveling Fellowship and a Merck / M.I.T. Fellowship to do postdoctoral work at the Massachusetts Institute of Technology. He joined the Department of Neurobiology at the University of Massachusetts Medical School as a faculty member in October 2001.

Office: LRB 725
Phone: 508-856-6804
E-mail: Scott.Waddell@umassmed.edu
Keywords: Neurobiology, Organisms - Drosophila, Learning and Memory, Neural Plasticity, Genetics

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