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Current Opinion in Neurobiology Dec 2014A wealth of research has revealed that electrical synapses in the central nervous system exhibit a high degree of plasticity. Several recent studies, particularly in the... (Review)
Review
A wealth of research has revealed that electrical synapses in the central nervous system exhibit a high degree of plasticity. Several recent studies, particularly in the retina and inferior olive, highlight this plasticity. Three classes of mechanisms can alter electrical coupling over time courses ranging from milliseconds to days. Changes of membrane conductance through synaptic input or spiking activity shunt current and decouple neurons on the millisecond time scale. Such activity can also alter coupling symmetry, rectifying electrical synapses. More stable rectification can be accomplished through molecular asymmetry of the synapse itself. On the minutes time scale, changes in connexin phosphorylation can change coupling quasi-stably with an order of magnitude dynamic range. On the hours to days time scale, changes in expression level of connexins alter coupling through the course of circadian time, over developmental time, or in response to tissue injury. Combined, all of these mechanisms allow electrical coupling to be highly dynamic, changing in response to demands at the whole network level, in small portions of a network, or at the level of an individual synapse.
Topics: Animals; Electrical Synapses; Humans; Nerve Net; Neurons; Synaptic Transmission
PubMed: 24955544
DOI: 10.1016/j.conb.2014.05.011 -
Frontiers in Cellular Neuroscience 2019Invasion of an action potential (AP) to presynaptic terminals triggers calcium dependent vesicle fusion in a relatively short time window, about a millisecond, after the... (Review)
Review
Invasion of an action potential (AP) to presynaptic terminals triggers calcium dependent vesicle fusion in a relatively short time window, about a millisecond, after the onset of the AP. This allows fast and precise information transfer from neuron to neuron by means of synaptic transmission and phasic mediator release. However, at some synapses a single AP or a short burst of APs can generate delayed or asynchronous synaptic release lasting for tens or hundreds of milliseconds. Understanding the mechanisms underlying asynchronous release (AR) is important, since AR can better recruit extrasynaptic metabotropic receptors and maintain a high level of neurotransmitter in the extracellular space for a substantially longer period of time after presynaptic activity. Over the last decade substantial work has been done to identify the presynaptic calcium sensor that may be involved in AR. Several models have been suggested which may explain the long lasting presynaptic calcium elevation a prerequisite for prolonged delayed release. However, the presynaptic mechanisms underlying asynchronous vesicle release are still not well understood. In this review article, we provide an overview of the current state of knowledge on the molecular components involved in delayed vesicle fusion and in the maintenance of sufficient calcium concentration to trigger AR. In addition, we discuss possible alternative models that may explain intraterminal calcium dynamics underlying AR.
PubMed: 30809127
DOI: 10.3389/fncel.2019.00028 -
Frontiers in Cellular Neuroscience 2019The axon provides a sole output of the neuron which propagates action potentials reliably to the axon terminal and transmits neuronal information to the postsynaptic... (Review)
Review
The axon provides a sole output of the neuron which propagates action potentials reliably to the axon terminal and transmits neuronal information to the postsynaptic neuron across the synapse. A classical view of neuronal signaling is based on these two processes, namely binary (all or none) signaling along the axon and graded (tunable) signaling at the synapse. Recent studies, however, have revealed that the excitability of the axon is subject to dynamic tuning for a short period after axonal action potentials. This was first described as post-spike hyperexcitability, as measured by the changes in stimulus threshold for a short period after an action potential. Later on, direct recordings from central nervous system (CNS) axons or axon terminals using subcellular patch-clamp recording showed that axonal spikes are often followed by afterdepolarization (ADP) lasting for several tens of milliseconds and has been suggested to mediate post-spike hyperexcitability. In this review article, I focused on the mechanisms as well as the functional significance of ADP in fine-scale modulation of axonal spike signaling in the CNS, with special reference to hippocampal mossy fibers, one of the best-studied CNS axons. As a common basic mechanism underlying axonal ADP, passive propagation by the capacitive discharge of the axonal membrane as well as voltage-dependent K conductance underlies the generation of ADP. Small but prolonged axonal ADP lasting for several tens of milliseconds may influence the subsequent action potential and transmitter release from the axon terminals. Both duration and amplitude of axonal spike are subject to such modulation by preceding action potential-ADP sequence, deviating from the conventional assumption of digital nature of axonal spike signaling. Impact on the transmitter release is also discussed in the context of axonal spike plasticity. Axonal spike is subject to dynamic control on a fine-scale and thereby contributes to the short-term plasticity at the synapse.
PubMed: 31555100
DOI: 10.3389/fncel.2019.00407 -
Proceedings of the National Academy of... Feb 2023Cells throughout the human body detect mechanical forces. While it is known that the rapid (millisecond) detection of mechanical forces is mediated by force-gated ion...
Cells throughout the human body detect mechanical forces. While it is known that the rapid (millisecond) detection of mechanical forces is mediated by force-gated ion channels, a detailed quantitative understanding of cells as sensors of mechanical energy is still lacking. Here, we combine atomic force microscopy with patch-clamp electrophysiology to determine the physical limits of cells expressing the force-gated ion channels (FGICs) Piezo1, Piezo2, TREK1, and TRAAK. We find that, depending on the ion channel expressed, cells can function either as proportional or nonlinear transducers of mechanical energy and detect mechanical energies as little as ~100 fJ, with a resolution of up to ~1 fJ. These specific energetic values depend on cell size, channel density, and cytoskeletal architecture. We also make the surprising discovery that cells can transduce forces either nearly instantaneously (<1 ms) or with a substantial time delay (~10 ms). Using a chimeric experimental approach and simulations, we show how such delays can emerge from channel-intrinsic properties and the slow diffusion of tension in the membrane. Overall, our experiments reveal the capabilities and limits of cellular mechanosensing and provide insights into molecular mechanisms that different cell types may employ to specialize for their distinct physiological roles.
Topics: Humans; Mechanotransduction, Cellular; Ion Channels; Cytoskeleton
PubMed: 36795747
DOI: 10.1073/pnas.2215747120 -
NeuroImage Oct 2022Spontaneous neural activity in human as assessed with resting-state functional magnetic resonance imaging (fMRI) exhibits brain-wide coordinated patterns in the...
Spontaneous neural activity in human as assessed with resting-state functional magnetic resonance imaging (fMRI) exhibits brain-wide coordinated patterns in the frequency of < 0.1 Hz. However, understanding of fast brain-wide networks at the timescales of neuronal events (milliseconds to sub-seconds) and their spatial, spectral, and transitional characteristics remain limited due to the temporal constraints of hemodynamic signals. With milli-second resolution and whole-head coverage, scalp-based electroencephalography (EEG) provides a unique window into brain-wide networks with neuronal-timescale dynamics, shedding light on the organizing principles of brain functions. Using the state-of-the-art signal processing techniques, we reconstructed cortical neural tomography from resting-state EEG and extracted component-based co-activation patterns (cCAPs). These cCAPs revealed brain-wide intrinsic networks and their dynamics, indicating the configuration/reconfiguration of resting human brains into recurring and transitional functional states, which are featured with the prominent spatial phenomena of global patterns and anti-state pairs of co-(de)activations. Rich oscillational structures across a wide frequency band (i.e., 0.6 Hz, 5 Hz, and 10 Hz) were embedded in the nonstationary dynamics of these functional states. We further identified a superstructure that regulated between-state immediate and long-range transitions involving the entire set of identified cCAPs and governed a significant aspect of brain-wide network dynamics. These findings demonstrated how resting-state EEG data can be functionally decomposed using cCAPs to reveal rich dynamic structures of brain-wide human neural activations.
Topics: Brain; Brain Mapping; Electroencephalography; Humans; Magnetic Resonance Imaging; Rest
PubMed: 35820583
DOI: 10.1016/j.neuroimage.2022.119461 -
Science Advances Jun 2021Optical metasurfaces (OMSs) have shown unprecedented capabilities for versatile wavefront manipulations at the subwavelength scale. However, most well-established OMSs...
Optical metasurfaces (OMSs) have shown unprecedented capabilities for versatile wavefront manipulations at the subwavelength scale. However, most well-established OMSs are static, featuring well-defined optical responses determined by OMS configurations set during their fabrication, whereas dynamic OMS configurations investigated so far often exhibit specific limitations and reduced reconfigurability. Here, by combining a thin-film piezoelectric microelectromechanical system (MEMS) with a gap-surface plasmon-based OMS, we develop an electrically driven dynamic MEMS-OMS platform that offers controllable phase and amplitude modulation of the reflected light by finely actuating the MEMS mirror. Using this platform, we demonstrate MEMS-OMS components for polarization-independent beam steering and two-dimensional (2D) focusing with high modulation efficiencies (~50%), broadband operation (~20% near the operating wavelength of 800 nanometers), and fast responses (<0.4 milliseconds). The developed MEMS-OMS platform offers flexible solutions for realizing complex dynamic 2D wavefront manipulations that could be used in reconfigurable and adaptive optical networks and systems.
PubMed: 34162551
DOI: 10.1126/sciadv.abg5639 -
Neurophotonics Apr 2024The development of genetically encoded fluorescent indicators of neural activity with millisecond dynamics has generated demand for ever faster two-photon (2P) imaging...
SIGNIFICANCE
The development of genetically encoded fluorescent indicators of neural activity with millisecond dynamics has generated demand for ever faster two-photon (2P) imaging systems, but acoustic and mechanical beam scanning technologies are approaching fundamental limits. We demonstrate that potassium tantalate niobate (KTN) electro-optical deflectors (EODs), which are not subject to the same fundamental limits, are capable of ultrafast two-dimensional (2D) 2P imaging .
AIM
To determine if KTN-EODs are suitable for 2P imaging, compatible with 2D scanning, and capable of ultrafast imaging of genetically encoded indicators with millisecond dynamics.
APPROACH
The performance of a commercially available KTN-EOD was characterized across a range of drive frequencies and laser parameters relevant to 2P microscopy. A second KTN-EOD was incorporated into a dual-axis scan module, and the system was validated by imaging signals from ASAP3, a genetically encoded voltage indicator.
RESULTS
Optimal KTN-EOD deflection of laser light with a central wavelength of 960 nm was obtained up to the highest average powers and pulse intensities tested (power: 350 mW; pulse duration: 118 fs). Up to 32 resolvable spots per line at a 560 kHz line scan rate could be obtained with single-axis deflection. The complete dual-axis EO 2P microscope was capable of imaging a by field-of-view at over 10 kHz frame rate with lateral resolution. We demonstrate imaging of neurons expressing ASAP3 with high temporal resolution.
CONCLUSIONS
We demonstrate the suitability of KTN-EODs for ultrafast 2P cellular imaging , providing a foundation for future high-performance microscopes to incorporate emerging advances in KTN-based scanning technology.
PubMed: 38841422
DOI: 10.1117/1.NPh.11.2.025005 -
International Journal of Molecular... Mar 2019X-ray crystallographic methods can be used to visualize macromolecules at high resolution. This provides an understanding of molecular mechanisms and an insight into... (Review)
Review
X-ray crystallographic methods can be used to visualize macromolecules at high resolution. This provides an understanding of molecular mechanisms and an insight into drug development and rational engineering of enzymes used in the industry. Although conventional synchrotron-based X-ray crystallography remains a powerful tool for understanding molecular function, it has experimental limitations, including radiation damage, cryogenic temperature, and static structural information. Serial femtosecond crystallography (SFX) using X-ray free electron laser (XFEL) and serial millisecond crystallography (SMX) using synchrotron X-ray have recently gained attention as research methods for visualizing macromolecules at room temperature without causing or reducing radiation damage, respectively. These techniques provide more biologically relevant structures than traditional X-ray crystallography at cryogenic temperatures using a single crystal. Serial femtosecond crystallography techniques visualize the dynamics of macromolecules through time-resolved experiments. In serial crystallography (SX), one of the most important aspects is the delivery of crystal samples efficiently, reliably, and continuously to an X-ray interaction point. A viscous delivery medium, such as a carrier matrix, dramatically reduces sample consumption, contributing to the success of SX experiments. This review discusses the preparation and criteria for the selection and development of a sample delivery medium and its application for SX.
Topics: Crystallization; Crystallography, X-Ray; Drug Development; Electrons; Lasers; Macromolecular Substances; Specimen Handling; Viscosity
PubMed: 30836596
DOI: 10.3390/ijms20051094 -
Current Biology : CB Aug 2019Monovision is a common prescription lens correction for presbyopia [1]. Each eye is corrected for a different distance, causing one image to be blurrier than the other....
Monovision is a common prescription lens correction for presbyopia [1]. Each eye is corrected for a different distance, causing one image to be blurrier than the other. Millions of people have monovision corrections, but little is known about how interocular blur differences affect motion perception. Here, we report that blur differences cause a previously unknown motion illusion that makes people dramatically misperceive the distance and three-dimensional direction of moving objects. The effect occurs because the blurry and sharp images are processed at different speeds. For moving objects, the mismatch in processing speed causes a neural disparity, which results in the misperceptions. A variant of a 100-year-old stereo-motion phenomenon called the Pulfrich effect [2], the illusion poses an apparent paradox: blur reduces contrast, and contrast reductions are known to cause neural processing delays [3-6], but our results indicate that blurry images are processed milliseconds more quickly. We resolve the paradox with known properties of the early visual system, show that the misperceptions can be severe enough to impact public safety, and demonstrate that the misperceptions can be eliminated with novel combinations of non-invasive ophthalmic interventions. The fact that substantial perceptual errors are caused by millisecond differences in processing speed highlights the exquisite temporal calibration required for accurate perceptual estimation. The motion illusion-the reverse Pulfrich effect-and the paradigm we use to measure it should help reveal how optical and image properties impact temporal processing, an important but understudied issue in vision and visual neuroscience.
Topics: Adult; Depth Perception; Female; Humans; Illusions; Male; Motion; Motion Perception; Presbyopia; Vision, Monocular; Young Adult
PubMed: 31353183
DOI: 10.1016/j.cub.2019.06.070 -
Frontiers in Neuroscience 2021Across sleep and wakefulness, brain function requires inter-neuronal interactions lasting beyond seconds. Yet, most studies of neural circuit connectivity focus on... (Review)
Review
Across sleep and wakefulness, brain function requires inter-neuronal interactions lasting beyond seconds. Yet, most studies of neural circuit connectivity focus on millisecond-scale interactions mediated by the classic fast transmitters, GABA and glutamate. In contrast, neural circuit roles of the largest transmitter family in the brain-the slow-acting peptide transmitters-remain relatively overlooked, or described as "modulatory." Neuropeptides may efficiently implement sustained neural circuit connectivity, since they are not rapidly removed from the extracellular space, and their prolonged action does not require continuous presynaptic firing. From this perspective, we review actions of evolutionarily-conserved neuropeptides made by brain-wide-projecting hypothalamic neurons, focusing on lateral hypothalamus (LH) neuropeptides essential for stable consciousness: the orexins/hypocretins. Action potential-dependent orexin release inside and outside the hypothalamus evokes slow postsynaptic excitation. This excitation does not arise from modulation of classic neurotransmission, but involves direct action of orexins on their specific G-protein coupled receptors (GPCRs) coupled to ion channels. While millisecond-scale, GABA/glutamate connectivity within the LH may not be strong, re-assessing LH microcircuits from the peptidergic viewpoint is consistent with slow local microcircuits. The sustained actions of neuropeptides on neuronal membrane potential may enable core brain functions, such as temporal integration and the creation of lasting permissive signals that act as "eligibility traces" for context-dependent information routing and plasticity. The slowness of neuropeptides has unique advantages for efficient neuronal processing and feedback control of consciousness.
PubMed: 33776641
DOI: 10.3389/fnins.2021.644313