Pre- and post-synaptic mechanisms of synaptic strength homeostasis revealed by Slowpoke and Shaker K+ channel mutations in Drosophila

Jihye Lee; Atsushi Ueda; Chun-Fang Wu

doi:10.1016/j.neuroscience.2008.04.043

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Pre- and post-synaptic mechanisms of synaptic strength homeostasis revealed by Slowpoke and Shaker K+ channel mutations in Drosophila

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Pre- and post-synaptic mechanisms of synaptic strength homeostasis revealed by Slowpoke and Shaker K+ channel mutations in Drosophila

Jihye Lee, Atsushi Ueda and Chun-Fang Wu

Neuroscience, Vol.154(4), pp.1283-1296

07/17/2008

DOI: 10.1016/j.neuroscience.2008.04.043

PMCID: PMC3362398

PMID: 18539401

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https://www.ncbi.nlm.nih.gov/pmc/articles/3362398View

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Abstract

We report naturally occurring, systematic variations in synaptic strength at neuromuscular junctions along the dorsal-ventral (D-V) axis of the\nDrosophila\nlarval body wall. These gradual changes were correlated with differences in presynaptic neurotransmitter release regulated by nerve terminal excitability and in postsynaptic receptor composition influencing miniature excitatory junctional potential (mEJP) amplitude. Surprisingly, synaptic strength and D-V differentials at physiological Ca\n2+\nlevels were not significantly altered in\nslowpoke\n(\nslo\n) and\nShaker\n(\nSh\n) mutants, despite their defects in two major repolarizing forces, Ca\n2+\n-activated Slo (BK) and voltage-activated Sh currents, respectively. However, lowering [Ca\n2+\n]\no\nlevels revealed greatly altered synaptic mechanisms in these mutants, indicated by drastically enhanced EJPs in\nSh\nbut paradoxically reduced EJPs in\nslo\n. Removal of Sh current in\nslo\nmutants by 4-aminopyridine blockade or by combining\nslo\nwith\nSh\nmutations led to strikingly increased synaptic transmission, suggesting upregulation of presynaptic Sh current to limit excessive neurotransmitter release in the absence of Slo current. In addition,\nslo\nmutants displayed altered immunoreactivity intensity ratio between DGluRIIA and DGluRIIB receptor subunits. This modified receptor composition caused smaller mEJP amplitudes, further preventing excessive transmission in the absence of Slo current. Such compensatory regulation was prevented by\nrutabaga\n(\nrut\n) adenylyl cyclase mutations in\nrut slo\ndouble mutants, demonstrating a novel role of\nrut\nin homeostatic plasticity, in addition to its well-established function in learning behavior.

rutabaga adenylyl cyclase

Membrane excitability

Postsynaptic receptor composition

Synaptic strength

cAMP

dorsal-ventral differentials

Details

Title: Subtitle: Pre- and post-synaptic mechanisms of synaptic strength homeostasis revealed by Slowpoke and Shaker K+ channel mutations in Drosophila
Creators: Jihye Lee - Interdisciplinary Program in Neuroscience, The University of Iowa, Iowa City, IA 52242, USA
Atsushi Ueda - Department of Biology, The University of Iowa, Iowa City, IA 52242, USA
Chun-Fang Wu - Interdisciplinary Program in Neuroscience, The University of Iowa, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: Neuroscience, Vol.154(4), pp.1283-1296
DOI: 10.1016/j.neuroscience.2008.04.043
PMID: 18539401
PMCID: PMC3362398
NLM abbreviation: Neuroscience
ISSN: 0306-4522
eISSN: 1873-7544
Grant note: R01 NS026528-17 || NS / National Institute of Neurological Disorders and Stroke : NINDS\nP01 HD018577-220003 || HD / National Institute of Child Health & Human Development : NICHD\nP01 HD018577-210003 || HD / National Institute of Child Health & Human Development : NICHD\nR01 NS026528-16 || NS / National Institute of Neurological Disorders and Stroke : NINDS
Language: English
Date published: 07/17/2008
Academic Unit: Iowa Neuroscience Institute; Biology
Record Identifier: 9984070746502771

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