scholarly journals Chemical delivery array with millisecond neurotransmitter release

2016 ◽  
Vol 2 (11) ◽  
pp. e1601340 ◽  
Author(s):  
Amanda Jonsson ◽  
Theresia Arbring Sjöström ◽  
Klas Tybrandt ◽  
Magnus Berggren ◽  
Daniel T. Simon
Keyword(s):  
Neurological Disorders ◽  
Neurotransmitter Release ◽  
High Speed ◽  
Synaptic Function ◽  
Controlled Delivery ◽  
Ion Pump ◽  
Delivery Device ◽  
Organic Electronic ◽  
Control Electrode ◽  
Neural Signaling

Technologies that restore or augment dysfunctional neural signaling represent a promising route to deeper understanding and new therapies for neurological disorders. Because of the chemical specificity and subsecond signaling of the nervous system, these technologies should be able to release specific neurotransmitters at specific locations with millisecond resolution. We have previously demonstrated an organic electronic lateral electrophoresis technology capable of precise delivery of charged compounds, such as neurotransmitters. However, this technology, the organic electronic ion pump, has been limited to a single delivery point, or several simultaneously addressed outlets, with switch-on speeds of seconds. We report on a vertical neurotransmitter delivery device, configured as an array with individually controlled delivery points and a temporal resolution of 50 ms. This is achieved by supplementing lateral electrophoresis with a control electrode and an ion diode at each delivery point to allow addressing and limit leakage. By delivering local pulses of neurotransmitters with spatiotemporal dynamics approaching synaptic function, the high-speed delivery array promises unprecedented access to neural signaling and a path toward biochemically regulated neural prostheses.

scholarly journals Intracellular Ca2+ Release and Synaptic Plasticity: A Tale of Many Stores

2018 ◽  
Vol 25 (3) ◽  
pp. 208-226 ◽  
Author(s):  
Zahid Padamsey ◽  
William J. Foster ◽  
Nigel J. Emptage
Keyword(s):  
Endoplasmic Reticulum ◽  
Synaptic Plasticity ◽  
Synaptic Function ◽  
Intracellular Organelles ◽  
Short And Long Term ◽  
Central Synapses ◽  
Neural Signaling ◽  
Temporal Extent

Ca2+ is an essential trigger for most forms of synaptic plasticity. Ca2+ signaling occurs not only by Ca2+ entry via plasma membrane channels but also via Ca2+ signals generated by intracellular organelles. These organelles, by dynamically regulating the spatial and temporal extent of Ca2+ elevations within neurons, play a pivotal role in determining the downstream consequences of neural signaling on synaptic function. Here, we review the role of three major intracellular stores: the endoplasmic reticulum, mitochondria, and acidic Ca2+ stores, such as lysosomes, in neuronal Ca2+ signaling and plasticity. We provide a comprehensive account of how Ca2+ release from these stores regulates short- and long-term plasticity at the pre- and postsynaptic terminals of central synapses.

scholarly journals Molecular Mechanisms of Fast Neurotransmitter Release

2018 ◽  
Vol 47 (1) ◽  
pp. 469-497 ◽  
Author(s):  
Axel T. Brunger ◽  
Ucheor B. Choi ◽  
Ying Lai ◽  
Jeremy Leitz ◽  
Qiangjun Zhou
Keyword(s):  
Synaptic Vesicle ◽  
Neurotransmitter Release ◽  
High Speed ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Vesicle Fusion ◽  
Synaptic Proteins ◽  
Functional Studies ◽  
Protein Receptors ◽  
Synaptic Vesicle Fusion

This review summarizes current knowledge of synaptic proteins that are central to synaptic vesicle fusion in presynaptic active zones, including SNAREs (soluble N-ethylmaleimide sensitive factor attachment protein receptors), synaptotagmin, complexin, Munc18 (mammalian uncoordinated-18), and Munc13 (mammalian uncoordinated-13), and highlights recent insights in the cooperation of these proteins for neurotransmitter release. Structural and functional studies of the synaptic fusion machinery suggest new molecular models of synaptic vesicle priming and Ca2+-triggered fusion. These studies will be a stepping-stone toward answering the question of how the synaptic vesicle fusion machinery achieves such high speed and sensitivity.

scholarly journals Mitochondrial trafficking and anchoring in neurons: New insight and implications

2014 ◽  
Vol 204 (7) ◽  
pp. 1087-1098 ◽  
Author(s):  
Zu-Hang Sheng
Keyword(s):  
Energy Source ◽  
Recent Work ◽  
Neurological Disorders ◽  
Synaptic Function ◽  
Local Energy ◽  
Synaptic Physiology ◽  
Mitochondrial Motility ◽  
Mitochondrial Trafficking ◽  
And Function ◽  
Neuron Growth

Mitochondria are essential organelles for neuronal growth, survival, and function. Neurons use specialized mechanisms to drive mitochondria transport and to anchor them in axons and at synapses. Stationary mitochondria buffer intracellular Ca2+ and serve as a local energy source by supplying ATP. The balance between motile and stationary mitochondria responds quickly to changes in axonal and synaptic physiology. Defects in mitochondrial transport are implicated in the pathogenesis of several major neurological disorders. Recent work has provided new insight in the regulation of microtubule-based mitochondrial trafficking and anchoring, and on how mitochondrial motility influences neuron growth, synaptic function, and mitophagy.

scholarly journals S6 kinase localizes to the presynaptic active zone and functions with PDK1 to control synapse development

2011 ◽  
Vol 194 (6) ◽  
pp. 921-935 ◽  
Author(s):  
Ling Cheng ◽  
Cody Locke ◽  
Graeme W. Davis
Keyword(s):  
Active Zone ◽  
Neurotransmitter Release ◽  
Synaptic Function ◽  
Growth Factor Signaling ◽  
Neuron Type ◽  
S6 Kinase ◽  
Neuronal Dendrites ◽  
Presynaptic Boutons ◽  
Presynaptic Active Zone ◽  
Presynaptic Protein

The dimensions of neuronal dendrites, axons, and synaptic terminals are reproducibly specified for each neuron type, yet it remains unknown how these structures acquire their precise dimensions of length and diameter. Similarly, it remains unknown how active zone number and synaptic strength are specified relative the precise dimensions of presynaptic boutons. In this paper, we demonstrate that S6 kinase (S6K) localizes to the presynaptic active zone. Specifically, S6K colocalizes with the presynaptic protein Bruchpilot (Brp) and requires Brp for active zone localization. We then provide evidence that S6K functions downstream of presynaptic PDK1 to control synaptic bouton size, active zone number, and synaptic function without influencing presynaptic bouton number. We further demonstrate that PDK1 is also a presynaptic protein, though it is distributed more broadly. We present a model in which synaptic S6K responds to local extracellular nutrient and growth factor signaling at the synapse to modulate developmental size specification, including cell size, bouton size, active zone number, and neurotransmitter release.

scholarly journals Soft iontronic delivery devices based on an intrinsically stretchable ion selective membrane

2021 ◽  
Author(s):  
Dennis Cherian ◽  
Samuel Lienemann ◽  
Tobias Abrahamsson ◽  
Nara Kim ◽  
Magnus Berggren ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Ion Exchange ◽  
Controlled Drug Delivery ◽  
Controlled Delivery ◽  
Ion Exchange Membranes ◽  
Delivery Device ◽  
Energy Devices ◽  
Skin Patch ◽  
Selective Membrane ◽  
Drug Delivery Devices

Abstract Implantable electronically controlled drug delivery devices can provide precision theraputic treatments by highly spatiotemporally controlled delivery. Iontronic delivery devices rely on the movement of ions rather than liquid, and can therefore achieve electronically controlled precision delivery in a compact setting without disturbing the microenvironment within the tissue with fluid flow. For maximum precision, the delivery device needs to be closely integrated into the tissue, which is challenging due to the mechanical mismatch between the soft tissue and the harder devices. Here we address this challenge by developing a soft and stretchable iontronic delivery device. By formulating an ink based on an in-house synthesized hyperbranched polyelectrolyte, water dispersed polyurethane, and a thickening agent, a viscous ink is developed for stencil patterning of soft ion exchange membranes. We use this ink for developing soft and stretchable delivery devices, which are characterized both in the relaxed and stretched state. We find that their functionality is preserved up to 100 % strain, with small variations in resistance due to the strain. Finally, we develop a skin patch to demonstrate the outstanding conformability of the developed device. The presented technology is attractive for future soft implantable delivery devices, and the stretchable ion exchange membranes may also find applications within wearable energy devices.

A new construction of a high-vacuum high-speed ion pump

1958 ◽  
Vol 8 (6) ◽  
pp. 746-747 ◽  
Author(s):  
Libor Pátý ◽  
Radmila Neužilová
Keyword(s):  
High Speed ◽  
High Vacuum ◽  
Ion Pump ◽  
New Construction

High-speed ion pump with a multipactor cathode—the multipactor ion pump

Vacuum ◽  
1983 ◽  
Vol 33 (6) ◽  
pp. 346
Keyword(s):  
High Speed ◽  
Ion Pump
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