Homeostatic Depression Shows Heightened Sensitivity to Synaptic Calcium
Synapses and circuits rely on homeostatic forms of regulation in order to transmit meaningful information. The Drosophila melanogaster neuromuscular junction (NMJ) is a well-studied synapse that shows robust homeostatic control of function. Most prior studies of homeostatic plasticity at the NMJ hav...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-05-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fncel.2021.618393/full |
| _version_ | 1818864285613293568 |
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| author | Catherine J. Yeates Catherine J. Yeates C. Andrew Frank C. Andrew Frank C. Andrew Frank |
| author_facet | Catherine J. Yeates Catherine J. Yeates C. Andrew Frank C. Andrew Frank C. Andrew Frank |
| author_sort | Catherine J. Yeates |
| collection | DOAJ |
| description | Synapses and circuits rely on homeostatic forms of regulation in order to transmit meaningful information. The Drosophila melanogaster neuromuscular junction (NMJ) is a well-studied synapse that shows robust homeostatic control of function. Most prior studies of homeostatic plasticity at the NMJ have centered on presynaptic homeostatic potentiation (PHP). PHP happens when postsynaptic muscle neurotransmitter receptors are impaired, triggering retrograde signaling that causes an increase in presynaptic neurotransmitter release. As a result, normal levels of evoked excitation are maintained. The counterpart to PHP at the NMJ is presynaptic homeostatic depression (PHD). Overexpression of the Drosophila vesicular glutamate transporter (VGlut) causes an increase in the amplitude of spontaneous events. PHD happens when the synapse responds to the challenge by decreasing quantal content (QC) during evoked neurotransmission—again, resulting in normal levels of postsynaptic excitation. We hypothesized that there may exist a class of molecules that affects both PHP and PHD. Impairment of any such molecule could hurt a synapse’s ability to respond to any significant homeostatic challenge. We conducted an electrophysiology-based screen for blocks of PHD. We did not observe a block of PHD in the genetic conditions screened, but we found loss-of-function conditions that led to a substantial deficit in evoked amplitude when combined with VGlut overexpression. The conditions causing this phenotype included a double heterozygous loss-of-function condition for genes encoding the inositol trisphosphate receptor (IP3R —itpr) and ryanodine receptor (RyR). IP3Rs and RyRs gate calcium release from intracellular stores. Pharmacological agents targeting IP3R and RyR recapitulated the genetic losses of these factors, as did lowering calcium levels from other sources. Our data are consistent with the idea that the homeostatic signaling process underlying PHD is especially sensitive to levels of calcium at the presynapse. |
| first_indexed | 2024-12-19T10:29:14Z |
| format | Article |
| id | doaj.art-7211046b49a546e3b9365c6636b093ee |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-19T10:29:14Z |
| publishDate | 2021-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-7211046b49a546e3b9365c6636b093ee2022-12-21T20:25:48ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022021-05-011510.3389/fncel.2021.618393618393Homeostatic Depression Shows Heightened Sensitivity to Synaptic CalciumCatherine J. Yeates0Catherine J. Yeates1C. Andrew Frank2C. Andrew Frank3C. Andrew Frank4Department of Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City, IA, United StatesInterdisciplinary Graduate Program in Neuroscience, University of Iowa, Iowa City, IA, United StatesDepartment of Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City, IA, United StatesInterdisciplinary Graduate Program in Neuroscience, University of Iowa, Iowa City, IA, United StatesIowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, IA, United StatesSynapses and circuits rely on homeostatic forms of regulation in order to transmit meaningful information. The Drosophila melanogaster neuromuscular junction (NMJ) is a well-studied synapse that shows robust homeostatic control of function. Most prior studies of homeostatic plasticity at the NMJ have centered on presynaptic homeostatic potentiation (PHP). PHP happens when postsynaptic muscle neurotransmitter receptors are impaired, triggering retrograde signaling that causes an increase in presynaptic neurotransmitter release. As a result, normal levels of evoked excitation are maintained. The counterpart to PHP at the NMJ is presynaptic homeostatic depression (PHD). Overexpression of the Drosophila vesicular glutamate transporter (VGlut) causes an increase in the amplitude of spontaneous events. PHD happens when the synapse responds to the challenge by decreasing quantal content (QC) during evoked neurotransmission—again, resulting in normal levels of postsynaptic excitation. We hypothesized that there may exist a class of molecules that affects both PHP and PHD. Impairment of any such molecule could hurt a synapse’s ability to respond to any significant homeostatic challenge. We conducted an electrophysiology-based screen for blocks of PHD. We did not observe a block of PHD in the genetic conditions screened, but we found loss-of-function conditions that led to a substantial deficit in evoked amplitude when combined with VGlut overexpression. The conditions causing this phenotype included a double heterozygous loss-of-function condition for genes encoding the inositol trisphosphate receptor (IP3R —itpr) and ryanodine receptor (RyR). IP3Rs and RyRs gate calcium release from intracellular stores. Pharmacological agents targeting IP3R and RyR recapitulated the genetic losses of these factors, as did lowering calcium levels from other sources. Our data are consistent with the idea that the homeostatic signaling process underlying PHD is especially sensitive to levels of calcium at the presynapse.https://www.frontiersin.org/articles/10.3389/fncel.2021.618393/fullsynapsehomeostasisdepressionDrosophila melanogasterNMJplasticity |
| spellingShingle | Catherine J. Yeates Catherine J. Yeates C. Andrew Frank C. Andrew Frank C. Andrew Frank Homeostatic Depression Shows Heightened Sensitivity to Synaptic Calcium Frontiers in Cellular Neuroscience synapse homeostasis depression Drosophila melanogaster NMJ plasticity |
| title | Homeostatic Depression Shows Heightened Sensitivity to Synaptic Calcium |
| title_full | Homeostatic Depression Shows Heightened Sensitivity to Synaptic Calcium |
| title_fullStr | Homeostatic Depression Shows Heightened Sensitivity to Synaptic Calcium |
| title_full_unstemmed | Homeostatic Depression Shows Heightened Sensitivity to Synaptic Calcium |
| title_short | Homeostatic Depression Shows Heightened Sensitivity to Synaptic Calcium |
| title_sort | homeostatic depression shows heightened sensitivity to synaptic calcium |
| topic | synapse homeostasis depression Drosophila melanogaster NMJ plasticity |
| url | https://www.frontiersin.org/articles/10.3389/fncel.2021.618393/full |
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