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Japan - Australia Collaborative Symposium:How can animal models inform us about human brain disease

開催日 2014/9/13
時間 15:00 - 17:00
会場 Room C(502)
Chairperson(s) Seong-Seng Tan / Seong-Seng Tan (Florey Institute of Neuroscience, University of Melbourne, Australia / Florey Institute of Neuroscience, University of Melbourne, Australia)
大隅 典子 / Noriko Osumi (東北大学大学院医学系研究科 / Department of Developmental Neuroscience, Center for Neuroscience, Tohoku University Graduate School of Medicine, Japan)

Attention-like defects in a Drosophila model of schizophrenia

  • S3-C-2-4
  • Bruno Van Swinderen:1 
  • 1:Queensland Brain Institute, Australia 

The neurodevelopmental hypothesis of schizophrenia suggests that the disorder is the result of disturbances in early neuronal development, which manifest as clinical symptoms when the brain matures around adolescence. We used the fruit-fly model, Drosophila melanogaster, to test whether altered dopamine (DA) function during development resulted in persistent behavioural defects in adult animals, with a focus on attention-like behaviours [1,2]. We found that transient activation of DA neurons during a critical window of fly brain development increased visual responsiveness in adult animals [3]. By activating DA neurons while simultaneously blocking their synaptic output, we found that these effects on DA function appear to be cell-autonomous rather than post-synaptic. We are currently using Drosophila genetic tools to uncover cellular pathways that are modulated by transient DA neuron activation during development.

To better study the neurodevelopmental hypotheses of schizophrenia in Drosophila, we have developed novel behavioural and electrophysiological assays that allow us to measure attention-like readouts in flies. We devised a visual competition paradigm for walking flies to study the effects of DA ontogeny on attention in adult animals. Since attention is most likely a whole-brain phenomenon involving effects on a millisecond timescale, we developed a multichannel brain recording preparation for behaving flies [4]. Tethered flies were positioned on an air-supported ball, surrounded by a virtual-reality visual environment that they could control by their walking behaviour. Local field potential (LFP) recordings taken from across the fly brain measured how the brain responded to competing visual stimuli. These paradigms reveal persistent attention-like defects as a consequence of transiently increased DA signaling during brain development.

1. van Swinderen, B. (2007) Science 315: 1590-1593.
2. van Swinderen, B. and Brembs, B. (2010). J. Neurosci 30(3):1003-14.
3. Calcagno, B., Eyles, D., van Alphen, B., van Swinderen, B. (2013) Trans Psych, 2: e2026
4. Paulk, A.C., Zhou, Y-Q, Stratton, P., Liu, L., van Swinderen, B. (2013) J Neurophys 110: 1703-1721.

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