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My recent scientific articles

bookA new book chapter!!!!

Extracellular Recordings of Synaptic Plasticity and Network Oscillations in Hippocampal Slices

Gaga Kochlamazashvili, Oleg Senkov, Alexander Dityatev

ABSTRACT Activity-dependent strengthening and weakening of synaptic weights, manifested as long-term potentiation 7 (LTP) and depression (LTD), are two major mechanisms that are thought to be involved in creating memory 8 traces in the brain. Oscillations of neuronal activity, especially in the y (4–12 Hz), g (30–100 Hz), and 9 "ripple" (130–200 Hz) frequency bands, are also fundamental phenomena that are believed to contribute to 10 learning and memory. However, the interplay between oscillations and plasticity is still not understood. These 11 brain phenomena are rarely considered together when synaptic plasticity is studied. In this chapter, we 12 summarize the existing knowledge in the field, describe protocols that can be used to induce LTP in seven 13 major excitatory synaptic pathways in hippocampal slices, and introduce a procedure to investigate synaptic 14 plasticity and induce high-frequency oscillations under one experimental paradigm. pdf

Published:01/2011; DOI:10.1007/7657_2011_4 In book: Neuronal Network Analysis, Concepts and Experimental Approaches, Publisher: Springer, Humana Press, pp.127-147

cover

We could win a cover by the Journal of Neuroscience!!!

Restoration of synaptic plasticity and learning in young and aged NCAM-deficient mice by enhancing neurotransmission mediated by GluN2A-containing NMDA receptors.

Kochlamazashvili G, Bukalo O, Senkov O, Salmen B, Gerardy-Schahn R, Engel AK, Schachner M, Dityatev A

Neural cell adhesion molecule (NCAM) is the predominant carrier of the unusual glycan polysialic acid (PSA). Deficits in PSA and/or NCAM expression cause impairments in hippocampal long-term potentiation and depression (LTP and LTD) and are associated with schizophrenia and aging. In this study, we show that impaired LTP in adult NCAM-deficient (NCAM(-/-)) mice is restored by increasing the activity of the NMDA subtype of glutamate receptor (GluN) through either reducing the extracellular Mg2+ concentration or applying d-cycloserine (DCS), a partial agonist of the GluN glycine binding site. Pharmacological inhibition of the GluN2A subtype reduced LTP to the same level in NCAM(-/-) and wild-type (NCAM(+/+)) littermate mice and abolished the rescue by DCS in NCAM(-/-) mice, suggesting that the effects of DCS are mainly mediated by GluN2A. The insufficient contribution of GluN to LTD in NCAM(-/-) mice was also compensated for by DCS. Furthermore, impaired contextual and cued fear conditioning levels were restored in NCAM(-/-) mice by administration of DCS before conditioning. In 12-month-old NCAM(-/-), but not NCAM(+/+) mice, there was a decline in LTP compared with 3-month-old mice that could be rescued by DCS. In 24-month-old mice of both genotypes, there was a reduction in LTP that could be fully restored by DCS in NCAM(+/+) mice but only partially restored in NCAM(-/-) mice. Thus, several deficiencies of NCAM(-/-) mice can be ameliorated by enhancing GluN2A-mediated neurotransmission with DCS. pdf

Published: "Journal of Neuroscience" , February 15, 32(7):2263-75, 2012

review

Review PSA-NCAM: Synaptic functions mediated by its interactions with proteoglycans and glutamate receptors.

Senkov O, Tikhobrazova O, Dityatev A

Dynamic regulation of glycosylation of the neural cell adhesion molecule (NCAM) by an unusual large negatively charged polysialic acid (PSA) is the major prerequisite for correct formation of brain circuitries during development and for normal synaptic plasticity, learning and memory in the adult. Traditionally, PSA is viewed as a de-adhesive highly hydrated molecule, which interferes with cell adhesion and promotes cellular/synaptic dynamics by steric hindrance. Analysis of synaptic functions of PSA-NCAM highlighted additional features of this molecule. First, PSA promotes interaction of NCAM with heparan sulfate proteoglycans and thus stimulates synaptogenesis. Second, PSA-NCAM modulates glutamate receptors: it restrains activity of extrasynaptic GluN2B-containing NMDA receptors and facilitates activity of a subset of AMPA receptors. Perturbation in polysialylation and/or NCAM expression in mouse models recapitulates many symptoms of human brain disorders such as schizophrenia, depression, anxiety and Alzheimer's disease. pdf

Published: Int J Biochem Cell Biol. Apr; 44(4):591-5, 2012

cover_pagetitlepage

We could win a coverpage by NEURON!!!

The Extracellular Matrix Molecule Hyaluronic Acid Regulates Hippocampal Synaptic Plasticity by Modulating Postsynaptic L-Type Ca(2+) Channels

Kochlamazashvili G, Henneberger C, Bukalo O, Dvoretskova E, Senkov O, Lievens PM, Westenbroek R, Engel AK, Catterall WA, Rusakov DA, Schachner M, Dityatev A.

Although the extracellular matrix plays an important role in regulating use-dependent synaptic plasticity, the underlying molecular mechanisms are poorly understood. Here we examined the synaptic function of hyaluronic acid (HA), a major component of the extracellular matrix. Enzymatic removal of HA with hyaluronidase reduced nifedipine-sensitive whole-cell Ca(2+) currents, decreased Ca(2+) transients mediated by L-type voltage-dependent Ca(2+) channels (L-VDCCs) in postsynaptic dendritic shafts and spines, and abolished an L-VDCC-dependent component of long-term potentiation (LTP) at the CA3-CA1 synapses in the hippocampus. Adding exogenous HA, either by bath perfusion or via local delivery near recorded synapses, completely rescued this LTP component. In a heterologous expression system, exogenous HA rapidly increased currents mediated by Ca(v)1.2, but not Ca(v)1.3, subunit-containing L-VDCCs, whereas intrahippocampal injection of hyaluronidase impaired contextual fear conditioning. Our observations unveil a previously unrecognized mechanism by which the perisynaptic extracellular matrix influences use-dependent synaptic plasticity through regulation of dendritic Ca(2+) channels. pdf

Published: "NEURON" , July 15, 67(1):116-128, 2010

 

NR2BNeural Cell Adhesion Molecule-Associated Polysialic Acid Regulates Synaptic Plasticity and Learning by Restraining the Signaling through GluN2B-Containing NMDA Receptors

Gaga Kochlamazashvili, Oleg Senkov, Sergei Grebenyuk, Catrina Robinson, Mei-Fang Xiao, Katharina Stummeyer, Rita Gerardy-Schahn, Andreas K. Engel, Larry Feig, Alexey Semyanov, Vishnu Suppiramaniam, Melitta Schachner, and Alexander Dityatev

The neural cell adhesion molecule (NCAM) is the predominant carrier of 2.8 polysialic acid (PSA) in the mammalian brain. Abnormalities in PSA and NCAM expression are associated with schizophrenia in humans and cause deficits in hippocampal synaptic plasticity and contextual fear conditioning in mice. Here, we show that PSA inhibits opening of recombinant NMDA receptors composed of GluN1/2B (NR1/NR2B) or GluN1/2A/2B (NR1/NR2A/NR2B) but not of GluN1/2A (NR1/NR2A) subunits. Deficits in NCAM/PSA increase GluN2B-mediated transmission and Ca2 transients in the CA1 region of the hippocampus. In line with elevation of GluN2B-mediated transmission, defects in long-term potentiation in the CA1region and contextual fear memory in NCAM/PSA-deficient mice are abrogated by application of a GluN2B selective antagonist. Furthermore, treatment with the glutamate scavenger glutamic-pyruvic transaminase, ablation of Ras-GRF1 (a mediator of GluN2B signaling to p38MAPK), or direct inhibition of hyperactive p38MAPK can restore impaired synaptic plasticity in brain slices lacking PSA/NCAM. Thus, PSA carried byNCAM regulates plasticity and learning by inhibition of the GluN2B-Ras-GRF1-p38MAPK signaling pathway. These findings implicate carbohydrates carried by adhesion molecules in modulating NMDA receptor signaling in the brain and demonstrate reversibility of cognitive deficits associated with ablation of a schizophrenia-related adhesion molecule. pdf

Published: "Journal of Neuroscience" , March 17, 30(11), 4171-4183, 2010

 

 

 

 
 

schizapaperA new paper!!!!

Plastic Brain

A short assay about new discoveries in a field of neuroscience investigating brain plasticity pdf

Published: "National Geographic" magazine, Rus Ed., May, 2013, p52

 

schizaNeurobic exercises - simple but effective brain fitness

A short practical assay about how to strengthen your mental power and memory by doing very simple mental exercises called neurobics pdf

Published: "HEALTH" magazine, Rus Ed., "Здоровье", №7, p52-53, 2010

schizaSchizophrenia - a Black Matter of the Brain

A review about the most misterious mental disorder - scizophrenia, which affects nearly 1% of population worldwide. I outlined main molecular and genetics mechanisms involved in development of this desease. pdf

Published: "Scientific American" magazine, Rus Ed., "В Мире Науки", №5, p47-55, 2010

smart_drugsRemember Everything. How To Extend Our Brain Capabilites?

A big practical review about modern approaches and techniques for enhancing cognitive functions, memory and learning. Vitamins, brainy food, "smart drugs", natural herbal supplements, phisical exercises, mnemonic training etc. pdf

Published: "HEALTH" magazine, Rus Ed., "Здоровье", №4, p48-52, 2010

epigeneticsEpigenetics: Re-write A Life-Code

A big deep-in-details review about how our everyday life-style can alter gene expression which can be inherited in generations via epigenetic mechanisms. pdf

Published: "HEALTH" magazine, Rus Ed., "Здоровье", №1, p62-64, 2010

smart_drugsDo We Need Drugs For Our Mind?

A review about so-called "smart-drugs" and other more natural ways to enhance our cognition, memory and learning. pdf

Published: "Scientific American" magazine, Rus Ed., "В Мире Науки", №12, p36-43, 2009

PTSDErase A Fearfu Memory: PTSD

A review about post-traumatic stress disorder (PTSD) and interview with Gregory Quirk and Joseph LeDoux.

Published: "GEO" magazine, Rus Ed., №9, p162-166, 2009

Genes-IIGenes We Change - II: Bad Habits And Epigenetics

A big review about influence of negative life-style factors, like alcohol consumption and tobacco smoking on human epigenome which leads to formation of different types of cancers and chronc disorders. pdf

Published: "Scientific American" magazine, Rus Ed., "В Мире Науки", №9, p48-57, 2009

23andMeBeginning Of Personal Genomics Era

An interview with Linda Avey, a CEO of one of the leading US personal genomics company "23andMe". pdf

Published: "Scientific American" magazine, Rus Ed., "В Мире Науки", №2, p68-72, 2009

genes-IGenes We Change - I

A review about a role of epigenetic and life-style factors in altering of gene expression which causes various diseases and disbalances fine tuning of many molecular signaling cascades in the cells. pdf

Published: "Scientific American" magazine, Rus Ed., "В Мире Науки", №11, p50-59, 2008

HelgolandHelgoland - A Blusted Paradise Island

A travel guide about amazingly beautiful and most visited German island - Helgoland in North Sea. pdf

Published: "GEO Traveler" magazine, Rus Ed., Summer issue, p66-70, 2009

HamburgHamburg - A Travel Guide

A travel guide about German city - Hamburg. pdf

Published: "National Geographic Traveler" magazine, Rus Ed., №4, p50-57, 2009

BuzsakiBrain Is Hyper-Complex Space-Time Translator - Or Parisian Interview with Dr. Buzsaki

An interview with one of the leading expert in the field of brain oscillations and their role in learning and memory. pdf

A full interview (about 1.5 hr of conversation) with Dr. Buzsaki (in English) can be found here

Published: "Scientific American" magazine, Rus Ed., "В Мире Науки", №10, p80-83, 2008

Useful links:
Buzsaki's lab
His book at Amazon.com
Brain Science Podcast #31: Brain Rhythms with György Buzsáki
10 Questions to György Buzsaki
Der Rhythmus der Gedanken, Sueddeutsche.de

FENS-2008FENS - European Neuroscience Forum, 2008, Geneva, Switzerland

A reportage about the FENS-2008 biggest in Europe neuroscience mmeting which took place in Geneva, Switzerland. pdf

Published: "Scientific American" magazine, Rus Ed., "В Мире Науки", №9, p90-91, 2008

BCIBrain-Computer Telekinesis

A review about brain-computer interfaces (BCI) in gaming industry. pdf

Published: "Scientific American" magazine, Rus Ed., "В Мире Науки", №6, p80-83, 2008

CeBIT-2008CeBIT - A Firework Of High Technologies

A reportage about the biggest IT fair in Europe, CeBIT-2008 in Hannover, Germany. pdf

Published: "Scientific American" magazine, Rus Ed., "В Мире Науки", №4, p92-93, 2008

schizaMistery Of The Chillon Castle

A reportage and photocaverage about a famouse Swiss castle Chillon. pdf

Published: "National Geographic" magazine, Rus Ed., №9, p64-70, 2008

 
 
 
     

 

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