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Activity-dependent global downscaling of evoked neurotransmitter release across glutamatergic inputs in Drosophila.

  • Karunanithi, Shanker1, 2
  • Lin, Yong Qi3
  • Odierna, G Lorenzo4
  • Menon, Hareesh5
  • Gonzalez, Juan Mena6
  • Neely, G Gregory3
  • Noakes, Peter G7, 4
  • Lavidis, Nickolas A4
  • Moorhouse, Andrew J2
  • van Swinderen, Bruno7
  • 1 Queensland Brain Institute, The University of Queensland, St. Lucia, QLD 4072, Australia. [email protected] , (Australia)
  • 2 School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia. , (Australia)
  • 3 Charles Perkins Centre and School of Life & Environmental Science. The University of Sydney, NSW 2006, Australia. , (Australia)
  • 4 School of Biomedical Science, The University of Queensland, St. Lucia, QLD 4072, Australia. , (Australia)
  • 5 School of Medical Science and Menzies Health Institute Queensland, Griffith University, Gold Coast Campus, QLD 4222, Australia. , (Australia)
  • 6 ARL Division of Neurobiology, University of Arizona, Tucson, Arizona 85721, USA.
  • 7 Queensland Brain Institute, The University of Queensland, St. Lucia, QLD 4072, Australia. , (Australia)
Published Article
Journal of Neuroscience
Society for Neuroscience
Publication Date
Sep 14, 2020
DOI: 10.1523/JNEUROSCI.0349-20.2020
PMID: 32928887


Within mammalian brain circuits, activity-dependent synaptic adaptations such as synaptic scaling stabilise neuronal activity in the face of perturbations. Stability afforded through synaptic scaling involves uniform scaling of quantal amplitudes across all synaptic inputs formed on neurons, as well as on the postsynaptic side. It remains unclear whether activity-dependent uniform scaling also operates within peripheral circuits. We tested for such scaling in a Drosophila larval neuromuscular circuit, where the muscle receives synaptic inputs from different motoneurons. We employed motoneuron-specific genetic manipulations to increase the activity of only one motoneuron and recordings of postsynaptic currents from inputs formed by the different motoneurons. We discovered an adaptation which caused uniform downscaling of evoked neurotransmitter release across all inputs through decreases in release probabilities. This 'presynaptic downscaling' maintained the relative differences in neurotransmitter release across all inputs around a homeostatic set point, caused a compensatory decrease in synaptic drive to the muscle affording robust and stable muscle activity, and was induced within hours. Presynaptic downscaling was associated with an activity-dependent increase in Drosophila vesicular glutamate transporter (DVGLUT) expression. Activity-dependent uniform scaling can therefore manifest also on the presynaptic side to produce robust and stable circuit outputs. Within brain circuits, uniform downscaling on the postsynaptic side is implicated in sleep- and memory-related processes. Our results suggest that evaluation of such processes might be broadened to include uniform downscaling on the presynaptic side.SIGNIFICANCE STATEMENTTo date, compensatory adaptations which stabilise target cell activity through activity-dependent global scaling have been observed only within central circuits, and on the postsynaptic side. Considering that maintenance of stable activity is imperative for the robust function of the nervous system as a whole, we tested whether activity-dependent global scaling could also manifest within peripheral circuits. We uncovered a compensatory adaptation which causes global scaling within a peripheral circuit and on the presynaptic side through uniform downscaling of evoked neurotransmitter release. Unlike in central circuits, uniform scaling maintains functionality over a wide rather than a narrow operational range, affording robust and stable activity. Activity-dependent global scaling therefore operates on both the pre- and postsynaptic sides to maintain target cell activity. Copyright © 2020 the authors.

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