scholarly journals Homeostatic Plasticity of Neurotransmitter Release Probability Is Determined by Presynaptic Calcium Influx

2011 ◽  
Vol 31 (31) ◽  
pp. 11097-11099 ◽  
Author(s):  
J. Subramanian
Keyword(s):  
Neurotransmitter Release ◽  
Calcium Influx ◽  
Homeostatic Plasticity ◽  
Release Probability ◽  
Presynaptic Calcium

scholarly journals Homeostatic synaptic depression is achieved through a regulated decrease in presynaptic calcium channel abundance

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Michael A Gaviño ◽  
Kevin J Ford ◽  
Santiago Archila ◽  
Graeme W Davis
Keyword(s):  
Synaptic Plasticity ◽  
Neuromuscular Junction ◽  
Action Potential ◽  
Calcium Channel ◽  
Neurotransmitter Release ◽  
Calcium Influx ◽  
Homeostatic Synaptic Plasticity ◽  
Action Potential Waveform ◽  
Presynaptic Calcium ◽  
Potential Waveform

Homeostatic signaling stabilizes synaptic transmission at the neuromuscular junction (NMJ) of Drosophila, mice, and human. It is believed that homeostatic signaling at the NMJ is bi-directional and considerable progress has been made identifying mechanisms underlying the homeostatic potentiation of neurotransmitter release. However, very little is understood mechanistically about the opposing process, homeostatic depression, and how bi-directional plasticity is achieved. Here, we show that homeostatic potentiation and depression can be simultaneously induced, demonstrating true bi-directional plasticity. Next, we show that mutations that block homeostatic potentiation do not alter homeostatic depression, demonstrating that these are genetically separable processes. Finally, we show that homeostatic depression is achieved by decreased presynaptic calcium channel abundance and calcium influx, changes that are independent of the presynaptic action potential waveform. Thus, we identify a novel mechanism of homeostatic synaptic plasticity and propose a model that can account for the observed bi-directional, homeostatic control of presynaptic neurotransmitter release.

scholarly journals MCTP is an ER-resident calcium sensor that stabilizes synaptic transmission and homeostatic plasticity

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Özgür Genç ◽  
Dion K Dickman ◽  
Wenpei Ma ◽  
Amy Tong ◽  
Richard D Fetter ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Molecular Mechanisms ◽  
Calcium Influx ◽  
Homeostatic Plasticity ◽  
Calcium Sensor ◽  
C2 Domains ◽  
Calcium Dependent ◽  
Disease Associations ◽  
Transmembrane Regions ◽  
Presynaptic Calcium

Presynaptic homeostatic plasticity (PHP) controls synaptic transmission in organisms from Drosophila to human and is hypothesized to be relevant to the cause of human disease. However, the underlying molecular mechanisms of PHP are just emerging and direct disease associations remain obscure. In a forward genetic screen for mutations that block PHP we identified mctp (Multiple C2 Domain Proteins with Two Transmembrane Regions). Here we show that MCTP localizes to the membranes of the endoplasmic reticulum (ER) that elaborate throughout the soma, dendrites, axon and presynaptic terminal. Then, we demonstrate that MCTP functions downstream of presynaptic calcium influx with separable activities to stabilize baseline transmission, short-term release dynamics and PHP. Notably, PHP specifically requires the calcium coordinating residues in each of the three C2 domains of MCTP. Thus, we propose MCTP as a novel, ER-localized calcium sensor and a source of calcium-dependent feedback for the homeostatic stabilization of neurotransmission.

Presynaptic calcium signals during neurotransmitter release: Detection with fluorescent indicators and other calcium chelators

1992 ◽  
Vol 86 (1-3) ◽  
pp. 129-134 ◽  
Author(s):  
GJ Augustine ◽  
EM Adler ◽  
MP Charlton ◽  
M Hans ◽  
D Swandulla ◽  
...  
Keyword(s):  
Neurotransmitter Release ◽  
Calcium Signals ◽  
Fluorescent Indicators ◽  
Presynaptic Calcium

scholarly journals GABAB receptor deficiency causes failure of neuronal homeostasis in hippocampal networks

2015 ◽  
Vol 112 (25) ◽  
pp. E3291-E3299 ◽  
Author(s):  
Irena Vertkin ◽  
Boaz Styr ◽  
Edden Slomowitz ◽  
Nir Ofir ◽  
Ilana Shapira ◽  
...  
Keyword(s):  
Neural Circuits ◽  
Gabab Receptor ◽  
Snare Complex ◽  
Homeostatic Plasticity ◽  
Calcium Flux ◽  
Neuronal Homeostasis ◽  
Protein Receptor ◽  
Presynaptic Calcium ◽  
Hippocampal Networks ◽  
Synaptic Vesicle Release

Stabilization of neuronal activity by homeostatic control systems is fundamental for proper functioning of neural circuits. Failure in neuronal homeostasis has been hypothesized to underlie common pathophysiological mechanisms in a variety of brain disorders. However, the key molecules regulating homeostasis in central mammalian neural circuits remain obscure. Here, we show that selective inactivation of GABAB, but not GABAA, receptors impairs firing rate homeostasis by disrupting synaptic homeostatic plasticity in hippocampal networks. Pharmacological GABAB receptor (GABABR) blockade or genetic deletion of the GB1a receptor subunit disrupts homeostatic regulation of synaptic vesicle release. GABABRs mediate adaptive presynaptic enhancement to neuronal inactivity by two principle mechanisms: First, neuronal silencing promotes syntaxin-1 switch from a closed to an open conformation to accelerate soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex assembly, and second, it boosts spike-evoked presynaptic calcium flux. In both cases, neuronal inactivity removes tonic block imposed by the presynaptic, GB1a-containing receptors on syntaxin-1 opening and calcium entry to enhance probability of vesicle fusion. We identified the GB1a intracellular domain essential for the presynaptic homeostatic response by tuning intermolecular interactions among the receptor, syntaxin-1, and the CaV2.2 channel. The presynaptic adaptations were accompanied by scaling of excitatory quantal amplitude via the postsynaptic, GB1b-containing receptors. Thus, GABABRs sense chronic perturbations in GABA levels and transduce it to homeostatic changes in synaptic strength. Our results reveal a novel role for GABABR as a key regulator of population firing stability and propose that disruption of homeostatic synaptic plasticity may underlie seizure's persistence in the absence of functional GABABRs.

scholarly journals LKB1 Regulates Mitochondria-Dependent Presynaptic Calcium Clearance and Neurotransmitter Release Properties at Excitatory Synapses along Cortical Axons

PLoS Biology ◽  
2016 ◽  
Vol 14 (7) ◽  
pp. e1002516 ◽  
Author(s):  
Seok-Kyu Kwon ◽  
Richard Sando ◽  
Tommy L. Lewis ◽  
Yusuke Hirabayashi ◽  
Anton Maximov ◽  
...  
Keyword(s):  
Neurotransmitter Release ◽  
Excitatory Synapses ◽  
Calcium Clearance ◽  
Presynaptic Calcium
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