Activity-Dependent Global Downscaling of Evoked Neurotransmitter Release across Glutamatergic Inputs in Drosophila

Activity-Dependent Global Downscaling of Evoked Neurotransmitter Release across Glutamatergic Inputs in Drosophila.

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.1523/JNEUROSCI.0349-20.2020
Journal or Publication Title: The Journal of Neuroscience
Volume: 40
Number: 42
Page Range: pp. 8025-8041
Date: 2020
Divisions: Directed Evolution
Depositing User: General Admin
Identification Number: 10.1523/JNEUROSCI.0349-20.2020
ISSN: 0270-6474
Date Deposited: 04 Jan 2021 00:34
Abstract:

Within mammalian brain circuits, activity-dependent synaptic adaptations, such as synaptic scaling, stabilize 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 used 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 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 STATEMENT To 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 presynaptic and postsynaptic sides to maintain target cell activity.

Creators:
Creators
Email
Karunanithi, Shanker
UNSPECIFIED
Lin, Yong Qi
UNSPECIFIED
Odierna, G. Lorenzo
UNSPECIFIED
Menon, Hareesh
UNSPECIFIED
Gonzalez, Juan Mena
UNSPECIFIED
Neely, G. Gregory
UNSPECIFIED
Noakes, Peter G.
UNSPECIFIED
Lavidis, Nickolas A.
UNSPECIFIED
Moorhouse, Andrew J.
UNSPECIFIED
van Swinderen, Bruno
UNSPECIFIED
Last Modified: 04 Jan 2021 00:34
URI: https://eprints.centenary.org.au/id/eprint/810

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