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 The active-zone protein Munc13 controls the use-dependence of presynaptic voltage-gated calcium channels

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Nathaniel Calloway ◽  
Géraldine Gouzer ◽  
Mingyu Xue ◽  
Timothy A Ryan
Keyword(s):  
Action Potential ◽  
Calcium Channel ◽  
Active Zone ◽  
Information Transfer ◽  
Calcium Influx ◽  
Single Action ◽  
Synaptic Modulation ◽  
Voltage Gated ◽  
Presynaptic Calcium

Presynaptic calcium channel function is critical for converting electrical information into chemical communication but the molecules in the active zone that sculpt this function are poorly understood. We show that Munc13, an active-zone protein essential for exocytosis, also controls presynaptic voltage-gated calcium channel (VGCC) function dictating their behavior during various forms of activity. We demonstrate that in vitro Munc13 interacts with voltage-VGCCs via a pair of basic residues in Munc13's C2B domain. We show that elimination of this interaction by either removal of Munc13 or replacement of Munc13 with a Munc13 C2B mutant alters synaptic VGCC's response to and recovery from high-frequency action potential bursts and alters calcium influx from single action potential stimuli. These studies illustrate a novel form of synaptic modulation and show that Munc13 is poised to profoundly impact information transfer at nerve terminals by controlling both vesicle priming and the trigger for exocytosis.

scholarly journals Elimination of the Actin-Binding Domain in Kelch-Like 1 Protein Induces T-Type Calcium Channel Modulation Only in the Presence of Action Potential Waveforms

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Kelly A. Aromolaran ◽  
Kelly A. Benzow ◽  
Leanne L. Cribbs ◽  
Michael D. Koob ◽  
Erika S. Piedras-Rentería
Keyword(s):  
Action Potential ◽  
Calcium Channel ◽  
Conformational Changes ◽  
Current Density ◽  
Calcium Influx ◽  
Direct Interaction ◽  
Recovery Phase ◽  
Actin Binding ◽  
Kinetic Properties ◽  
Action Potential Waveform

The Kelch-like 1 protein (KLHL1) is a neuronal actin-binding protein that modulates calcium channel function. It increases the current density of Cav3.2 (α1H) calcium channels via direct interaction with α1H and actin-F, resulting in biophysical changes in Cav3.2 currents and an increase in recycling endosomal activity with subsequent increased α1H channel number at the plasma membrane. Interestingly, removal of the actin-binding Kelch motif (ΔKelch) prevents the increase in Cav3.2 current density seen with wild-type KLHL1 when tested with normal square pulse protocols but does not preclude the effect when tested using action potential waveforms (AP). Here, we dissected the kinetic properties of the AP waveform that confer the mutant Kelch the ability to interact with Cav3.2 and induce an increase in calcium influx. We modified the action potential waveform by altering the slopes of repolarization and/or recovery from hyperpolarization or by changing the duration of the depolarization plateau or the hyperpolarization phase and tested the modulation of Cav3.2 by the mutant ΔKelch. Our results show that the recovery phase from hyperpolarization phase determines the conformational changes that allow the α1H subunit to properly interact with mutant KLHL1 lacking its actin-binding Kelch domains, leading to increased Ca influx.

scholarly journals KCNQ channels enable reliable presynaptic spiking and synaptic transmission at high-frequency

2019 ◽  
Author(s):  
Yihui Zhang ◽  
Dainan Li ◽  
Youad Darwish ◽  
Laurence O. Trussell ◽  
Hai Huang
Keyword(s):  
Action Potential ◽  
Synaptic Transmission ◽  
High Frequency ◽  
Calcium Influx ◽  
List Type ◽  
Kcnq Channels ◽  
Axon Terminals ◽  
Presynaptic Action ◽  
Action Potential Waveform ◽  
Potential Waveform

SUMMARYThe presynaptic action potential (AP) results in calcium influx which triggers neurotransmitter release. For this reason, the AP waveform is crucial in determining the timing and strength of synaptic transmission. The calyx of Held nerve terminals of rat show minimum changes in AP waveform during high-frequency AP firing. We found that the stability of the calyceal AP waveform requires KCNQ K+ channel activated during high-frequency spiking activity. High-frequency presynaptic spikes gradually led to accumulation of KCNQ channels in open states which kept interspike membrane potential sufficiently negative to maintain Na+ channel availability. Accordingly, blocking KCNQ channels during stimulus trains led to inactivation of presynaptic Na+, and to a lesser extent KV1 channels, thereby reducing the AP height and broadening AP duration. Thus, while KCNQ channels are generally thought to prevent hyperactivity of neurons, we find that in axon terminals these channels function to facilitate high-frequency firing needed for sensory coding.HIGHLIGHTSKCNQ channels are activated during high-frequency firingThe activity of KCNQ channels helps the recovery of Na+ and KV1 channels from inactivation and maintains action potential waveformReliable presynaptic action potential waveform preserves stable Ca2+ influx and reliable synaptic signaling

scholarly journals Action Potential Waveform Variability Limits Multi-Unit Separation in Freely Behaving Rats

PLoS ONE ◽  
2012 ◽  
Vol 7 (6) ◽  
pp. e38482 ◽  
Author(s):  
Peter Stratton ◽  
Allen Cheung ◽  
Janet Wiles ◽  
Eugene Kiyatkin ◽  
Pankaj Sah ◽  
...  
Keyword(s):  
Action Potential ◽  
Action Potential Waveform ◽  
Freely Behaving ◽  
Potential Waveform

scholarly journals Altered action potential waveform and shorter axonal initial segment in hiPSC-derived motor neurons with mutations in VRK1

2022 ◽  
pp. 105609
Author(s):  
Rémi Bos ◽  
Khalil Rihan ◽  
Patrice Quintana ◽  
Lara El-Bazzal ◽  
Nathalie Bernard-Marissal ◽  
...  
Keyword(s):  
Action Potential ◽  
Motor Neurons ◽  
Initial Segment ◽  
Axonal Initial Segment ◽  
Action Potential Waveform ◽  
Potential Waveform

scholarly journals Preterm Birth Impedes Structural and Functional Development of Cerebellar Purkinje Cells in the Developing Baboon Cerebellum

2020 ◽  
Vol 10 (12) ◽  
pp. 897
Author(s):  
Tara Barron ◽  
Jun Hee Kim
Keyword(s):  
Preterm Birth ◽  
Action Potential ◽  
Purkinje Cell ◽  
Purkinje Cells ◽  
Late Gestation ◽  
Cerebellar Development ◽  
Layer Width ◽  
Action Potential Waveform ◽  
Developmental Features ◽  
Potential Waveform

Human cerebellar development occurs late in gestation and is hindered by preterm birth. The fetal development of Purkinje cells, the primary output cells of the cerebellar cortex, is crucial for the structure and function of the cerebellum. However, morphological and electrophysiological features in Purkinje cells at different gestational ages, and the effects of neonatal intensive care unit (NICU) experience on cerebellar development are unexplored. Utilizing the non-human primate baboon cerebellum, we investigated Purkinje cell development during the last trimester of pregnancy and the effect of NICU experience following premature birth on developmental features of Purkinje cells. Immunostaining and whole-cell patch clamp recordings of Purkinje cells in the baboon cerebellum at different gestational ages revealed that molecular layer width, driven by Purkinje dendrite extension, drastically increased and refinement of action potential waveform properties occurred throughout the last trimester of pregnancy. Preterm birth followed by NICU experience for 2 weeks impeded development of Purkinje cells, including action potential waveform properties, synaptic input, and dendrite extension compared with age-matched controls. In addition, these alterations impact Purkinje cell output, reducing the spontaneous firing frequency in deep cerebellar nucleus (DCN) neurons. Taken together, the primate cerebellum undergoes developmental refinements during late gestation, and NICU experience following extreme preterm birth influences morphological and physiological features in the cerebellum that can lead to functional deficits.

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