A 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

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 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

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