Anton Sheinin

Tel Aviv University | TAU · Sagol School of Neuroscience

Background: Traumatic brain injury manifests itself in various forms, ranging from mild impairment of consciousness to severe coma and death. Traumatic brain injury remains one of the leading causes of morbidity and mortality. Currently, there is no therapy to reverse the effects associated with traumatic brain injury. New neuroprotective treatment...

Abelson non-receptor tyrosine kinases (Abl1 and Abl2) are established cellular signaling proteins, implicated in cytoskeletal reorganization essential for modulation of cell morphology and motility. During development of the central nervous system, Abl kinases play fundamental roles in neurulation and neurite outgrowth, relaying information from ax...

Dysregulated homeostasis of neural activity has been hypothesized to drive Alzheimer’s disease (AD) pathogenesis. AD begins with a decades-long presymptomatic phase, but whether homeostatic mechanisms already begin failing during this silent phase is unknown. We show that before the onset of memory decline and sleep disturbances, familial AD (fAD)...

Refractoriness is a fundamental property of excitable elements, such as neurons, indicating the probability for re-excitation in a given time lag, and is typically linked to the neuronal hyperpolarization following an evoked spike. Here we measured the refractory periods (RPs) in neuronal cultures and observed that an average anisotropic absolute R...

Refractoriness is a fundamental property of excitable elements, such as neurons, indicating the probability for re-excitation in a given time-lag, and is typically linked to the neuronal hyperpolarization following an evoked spike. Here we measured the refractory periods (RPs) in neuronal cultures and observed that anisotropic absolute RPs could ex...

Mechanical events and alterations in neuronal morphology that accompany neuronal activity have been observed for decades. However, no clear neurophysiological role, nor an agreed molecular mechanism relating these events to the electrochemical process, has been found. Here we hypothesized that intense, yet physiological, electrical activity in neur...

Alzheimer’s disease (AD) is characterized by progressive synaptic dysfunction, deterioration of neuronal transmission, and consequently neuronal death. Although there is no treatment for AD, exposure to enriched environment (EE) in mice, as well as physical and mental activity in human subjects have been shown to have a protective effect by slowing...

Amyloid beta (Aβ) peptides represent one of the most studied etiological factors of Alzheimer’s disease. Nevertheless, the effects elicited by different molecular forms of amyloid beta peptides widely vary between the studies, mostly depending on experimental conditions. Despite the enormous amount of accumulated evidences concerning the pathologic...

During hundreds of millions of years of evolution, insects have evolved some of the most efficient and robust sensing organs, often far more sensitive than their man-made equivalents. In this study, we demonstrate a hybrid bio-technological approach, integrating a locust tympanic ear with a robotic platform. Using an Ear-on-a-Chip method, we manage...

Individuals with spinal cord injury (SCI) usually suffer from permanent neurological deficits, while spontaneous recovery and therapeutic efficacy are limited. Here, we demonstrate that when given intranasally, exosomes derived from mesenchymal stem cells (MSC-Exo) could pass the blood brain barrier, and migrate to the injured spinal cord area. Fur...

Background & Aim Complete spinal cord injury (SCI) is a debilitating disease which usually leads to permanent functional impairments, with various complications and limited spontaneous recovery or effective treatment. Here, we report that in rats with complete SCI, intranasal administrations of mesenchymal stem cells-derived exosomes (MSC-Exo) coul...

Sequences and source of oligonucleotides used in this study.

List of gene names, gene IDs, symbols, and designations for the importin α family members.

List of genes that were significantly altered by the deletion of importin α5 and modulated by the FG-7142 anxiogenic treatment.

Data S1. Behavioral Profiling of Importin α1, α3, α4, α5, and α7 Knockout Mice, Related to Figure 1 Three groups per line: wild-type, heterozygous, knockouts. (A) Home-cage locomotion. Left panel: spontaneous activity during 48 hr with the respective average activity in counts per hr for dark (black box) and light periods (white box). (B and C) Op...

Importins mediate transport from synapse to soma and from cytoplasm to nucleus, suggesting that perturbation of importin-dependent pathways should have significant neuronal consequences. A behavioral screen on five importin α knockout lines revealed that reduced expression of importin α5 (KPNA1) in hippocampal neurons specifically decreases anxiety...

Physical models typically assume time-independent interactions, whereas neural networks and machine learning incorporate interactions that function as adjustable parameters. Here we demonstrate a new type of abundant cooperative nonlinear dynamics where learning is attributed solely to the nodes, instead of the network links which their number is s...

Neurons are the computational elements that compose the brain and their fundamental principles of activity are known for decades. According to the long-lasting computational scheme, each neuron sums the incoming electrical signals via its dendrites and when the membrane potential reaches a certain threshold the neuron typically generates a spike to...

The exact function of the polybasic juxtamembrane region (5RK) of the plasma membrane neuronal SNARE, syntaxin 1A (Syx), in vesicle exocytosis, although widely studied, is currently not clear. Here, we addressed the role of 5RK in Ca²⁺-triggered release, using our Syx-based intramolecular fluorescence resonance energy transfer (FRET) probe, which p...

Spinal cord injury (SCI), involving damaged axons and glial scar tissue, often culminates in irreversible impairments. Achieving substantial recovery following complete spinal cord transection remains an unmet challenge. Here, we report of implantation of an engineered 3D construct embedded with human oral mucosa stem cells (hOMSC) induced to secre...

Neural networks are composed of neurons and synapses, which are responsible for learning in a slow adaptive dynamical process. Here we experimentally show that neurons act like independent anisotropic multiplex hubs, which relay and mute incoming signals following their input directions. Theoretically, the observed information routing enriches the...

The Serine/threonine kinase AKT/PKB plays a fundamental role in a wide variety of neuronal functions, including neuronal cell development, axonal growth and synaptic plasticity. Multiple evidence link AKT signaling pathways to regulation of late phase long-term synaptic plasticity, synaptogenesis and spinogenesis, as well as long-term memory format...

Memory deficit is a common manifestation of age-related cognitive impairment, of which depression is a frequently occurring comorbidity. Previously, we developed a submissive (Sub) mouse line, validated as a model of depressive-like behavior. Using learning paradigms testing hippocampus-dependent spatial and nonspatial memory, we demonstrate here t...

Synaptic transmission relies on spatially and temporally coordinated multistep processes that allow neuronal communication; activity-dependent changes in synaptic transmission underlie synaptic plasticity. These processes are coordinated by a large number of specific proteins whose dynamic interactions, expression, and regulation define the efficac...

Alterations in the levels of synaptic proteins affect synaptic transmission and synaptic plasticity. However, the precise effects on neuronal network activity are still enigmatic. Here, we utilized microelectrode array (MEA) to elucidate how manipulation of the presynaptic release process affects the activity of neuronal networks. By combining phar...

Tomosyn, a syntaxin-binding protein, is known to inhibit vesicle priming and synaptic transmission via interference with the formation of SNARE complexes. Using a lentiviral vector, we specifically overexpressed tomosyn1 in hippocampal dentate gyrus neurons in adult mice. Mice were then subjected to spatial learning and memory tasks and electrophys...

Regulation of exocytosis by voltage-gated K(+) channels has classically been viewed as inhibition mediated by K(+) fluxes. We recently identified a new role for Kv2.1 in facilitating vesicle release from neuroendocrine cells, which is independent of K(+) flux. Here, we show that Kv2.1-induced facilitation of release is not restricted to neuroendocr...

Expression of Pax3 and Pax7 in hNPs derived PNS neurons. (A–F) Eight weeks old human NPs cultured on laminin for 12 days showing extensive neurite outgrowth expressing the PNS marker Peripherin (A, C and D, F) together with the dorsal markers, the transcription factors Pax3 (B and C) and Pax7 (E and F). Scale bars are indicated in representative im...

Expression of Tyrosine hydroxylase (TH) in hNPs derived PNS neurons. (A–C) Eight weeks old human NPs cultured on laminin for 12 days showing extensive neurite outgrowth expressing the PNS marker Peripherin (A and C) together with TH that is expressed by a small number of cells (B and C). Scale bar in C is representative. (1.83 MB TIF)

IKAP/hELP1 in hNPs derived PNS neurons in vivo. (A–E) Confocal micrographs showing the expression of IKAP/hELP1 in GFP+ together with the expression of human specific TAU (hTAU) in hNPs derived PNS neurons in the spinal cord of the chick embryo after 7 days of implantation. (E) Magnified area of the image in (A–D) showing orthogonal analysis of IKA...

Five weeks hNPs differentiation culture shows rosettes formation with miss localization of Islet-1. (A–C) Five weeks old hNPs expressing GFP was plated on laminin coated surface for 12 days in culture showing typical rosette structure (A). Note that Islet-1 expression (B) in these cells is cytoplasmic and not nuclear as expected, which may indicate...

The absence of a suitable cellular model is a major obstacle for the study of peripheral neuropathies. Human embryonic stem cells hold the potential to be differentiated into peripheral neurons which makes them a suitable candidate for this purpose. However, so far the potential of hESC to differentiate into derivatives of the peripheral nervous sy...

Endocannabinoids released from the postsynaptic neuronal membrane can activate presynaptic CB1 receptors and inhibit neurotransmitter release. In hippocampal slices, depolarization of the CA1 pyramidal neurons elicits an endocannabinoid-mediated inhibition of gamma-aminobutyric acid release known as depolarization-induced suppression of inhibition...

Ca2+ regulates multiple processes in nerve terminals, including synaptic vesicle recruitment, priming, and fusion. Munc13s, the mammalian homologs of Caenorhabditis elegans Unc13, are essential vesicle-priming proteins and contain multiple regulatory domains that bind second messengers such as diacylglycerol and Ca2+/calmodulin (Ca2+/CaM). Binding...

Kv channels inhibit release indirectly by hyperpolarizing membrane potential, but the significance of Kv channel interaction with the secretory apparatus is not known. The Kv2.1 channel is commonly expressed in the soma and dendrites of neurons, where it could influence the release of neuropeptides and neurotrophins, and in neuroendocrine cells, wh...

The M-type K(+) current (M-current), encoded by Kv7.2/3 (KCNQ2/3) K(+) channels, plays a critical role in regulating neuronal excitability because it counteracts subthreshold depolarizations. Here we have characterized the functions of pre- and postsynaptic M-channels using a novel Kv7.2/3 channel opener, NH6, which we synthesized as a new derivati...

The neuroprotective compound, 1-aminocyclopropanecarboxylic acid (ACPC), has been reported to act on the N-methyl-D-aspartate (NMDA) receptors simultaneously as a glycine binding site agonist and a glutamate binding site competitive antagonist. The complex kinetics of NMDA current changes measured by a whole-cell voltage clamp in rat hippocampal ne...

Recently, we have shown that 1-aminocyclopropanecarboxylic acid (ACPC) acts simultaneously as a high affinity full glycine agonist and a low affinity glutamate site competitive antagonist for NMDA receptor channels. In this paper, we have attempted to determine the subunit specificity and mechanism of action of a different putative cyclic partial a...