LTP expression mediated by autonomous activity of GluN2B-bound CaMKII.

Learning and memory are thought to require the induction and maintenance of long-term potentiation (LTP) of synaptic strength. LTP induction requires the Ca/calmodulin-dependent protein kinase II (CaMKII) but for structural rather than enzymatic functions. We show that the relevant structural function is regulated by CaMKII binding to the NMDA-type glutamate receptor subunit GluN2B.

Amyloid-β Causes NMDA Receptor Dysfunction and Dendritic Spine Loss through mGluR1 and AKAP150-Anchored Calcineurin Signaling.

Neuronal excitatory synapses are primarily located on small dendritic protrusions called spines. During synaptic plasticity underlying learning and memory, Ca influx through postsynaptic NMDA-type glutamate receptors (NMDARs) initiates signaling pathways that coordinate changes in dendritic spine structure and synaptic function. During long-term potentiation (LTP), high levels of NMDAR Ca influx promote increases in both synaptic strength and dendritic spine size through activation of Ca-dependent protein kinases.

Increasing the power and spectral efficiencies of an OFDM-based VLC system through multi-objective optimization.

The nonlinearity induced by light-emitting diodes in visible light communication (VLC) systems presents a challenge to the parametrization of orthogonal frequency division multiplexing (OFDM). The goal of the multi-objective optimization problem presented in this study is to maximize the transmitted power (superimposed LED bias-current and signal amplification) for both conventional and constant envelope (CE) OFDM while also maximizing spectral efficiency. The bit error rate (BER) metric is used to evaluate the optimization using the non-dominated sorting genetic algorithm II.

LTP induction by structural rather than enzymatic functions of CaMKII.

Learning and memory are thought to require hippocampal long-term potentiation (LTP), and one of the few central dogmas of molecular neuroscience that has stood undisputed for more than three decades is that LTP induction requires enzymatic activity of the Ca/calmodulin-dependent protein kinase II (CaMKII). However, as we delineate here, the experimental evidence is surprisingly far from conclusive. All previous interventions inhibiting enzymatic CaMKII activity and LTP also interfere with structural CaMKII roles, in particular binding to the NMDA-type glutamate receptor subunit GluN2B.

Decreased nitrosylation of CaMKII causes aging-associated impairments in memory and synaptic plasticity in mice.

CaMKII has molecular memory functions because transient calcium ion stimuli can induce long-lasting increases in its synaptic localization and calcium ion-independent (autonomous) activity, thereby leaving memory traces of calcium ion stimuli beyond their duration. The synaptic effects of two mechanisms that induce CaMKII autonomy are well studied: autophosphorylation at threonine-286 and binding to GluN2B. Here, we examined the neuronal functions of additional autonomy mechanisms: nitrosylation and oxidation of the CaMKII regulatory domain.

Increased / expression offsets Alzheimer Aβ-mediated toxicity and cognitive dysfunction.

Previously, we found that amyloid-beta (Aβ) competitively inhibits the kinesin motor protein KIF11 (Kinesin-5/Eg5), leading to defects in the microtubule network and in neurotransmitter and neurotrophin receptor localization and function. These biochemical and cell biological mechanisms for Aβ-induced neuronal dysfunction may underlie learning and memory defects in Alzheimer's disease (AD). Here, we show that KIF11 overexpression rescues Aβ-mediated decreases in dendritic spine density in cultured neurons and in long-term potentiation in hippocampal slices.

The Ca1.2 G406R mutation decreases synaptic inhibition and alters L-type Ca channel-dependent LTP at hippocampal synapses in a mouse model of Timothy Syndrome.

Genetic alterations in autism spectrum disorders (ASD) frequently disrupt balance between synaptic excitation and inhibition and alter plasticity in the hippocampal CA1 region. Individuals with Timothy Syndrome (TS), a genetic disorder caused by Ca1.2 L-type Ca channel (LTCC) gain-of function mutations, such as G406R, exhibit social deficits, repetitive behaviors, and cognitive impairments characteristic of ASD that are phenocopied in TS2-neo mice expressing G406R.

β-Amyloid disruption of LTP/LTD balance is mediated by AKAP150-anchored PKA and Calcineurin regulation of Ca-permeable AMPA receptors.

Regulated insertion and removal of postsynaptic AMPA glutamate receptors (AMPARs) mediates hippocampal long-term potentiation (LTP) and long-term depression (LTD) synaptic plasticity underlying learning and memory. In Alzheimer's disease β-amyloid (Aβ) oligomers may impair learning and memory by altering AMPAR trafficking and LTP/LTD balance. Importantly, Ca-permeable AMPARs (CP-AMPARs) assembled from GluA1 subunits are excluded from hippocampal synapses basally but can be recruited rapidly during LTP and LTD to modify synaptic strength and signaling.

Digital-to-analog converters for high-speed optical communications using frequency interleaving: impairments and characteristics.

Digital-to-analog converters (DACs) for high-speed optical communication systems based on CMOS technology have bandwidths lower than nowadays electro-optic components. A promising concept to circumvent this bottleneck is the frequency-interleaved DAC (FI-DAC) concept. In this paper, experimental results for the application of a 180 GS/s FI-DAC with 40 GHz analog bandwidth based on two DACs in a high-speed optical link are discussed and compared with simulation results.

Genetic knockout of the α7 nicotinic acetylcholine receptor gene alters hippocampal long-term potentiation in a background strain-dependent manner.

Reduced α7 nicotinic acetylcholine receptor (nAChR) function is linked to impaired hippocampal-dependent sensory processing and learning and memory in schizophrenia. While knockout of the Chrna7 gene encoding the α7nAChR on a C57/Bl6 background results in changes in cognitive measures, prior studies found little impact on hippocampal synaptic plasticity in these mice. However, schizophrenia is a multi-genic disorder where complex interactions between specific genetic mutations and overall genetic background may play a prominent role in determining phenotypic penetrance.

Inhibition of the Motor Protein Eg5/Kinesin-5 in Amyloid β-Mediated Impairment of Hippocampal Long-Term Potentiation and Dendritic Spine Loss.

Alzheimer's disease (AD) is characterized by neurofibrillary tangles, amyloid plaques, and neurodegeneration. However, this pathology is preceded by increased soluble amyloid beta (Aβ) 1-42 oligomers that interfere with the glutamatergic synaptic plasticity required for learning and memory, includingN-methyl-d-aspartate receptor (NMDAR)-dependent long-term potentiation (LTP). In particular, soluble Aβ(1-42) acutely inhibits LTP and chronically causes synapse loss.

Blocking leukotriene synthesis attenuates the pathophysiology of traumatic brain injury and associated cognitive deficits.

Neuroinflammation is a component of secondary injury following traumatic brain injury (TBI) that can persist beyond the acute phase. Leukotrienes are potent, pro-inflammatory lipid mediators generated from membrane phospholipids. In the absence of injury, leukotrienes are undetectable in the brain, but after trauma they are rapidly synthesized by a transcellular event involving infiltrating neutrophils and endogenous brain cells.

Autonomous CaMKII mediates both LTP and LTD using a mechanism for differential substrate site selection.

Traditionally, hippocampal long-term potentiation (LTP) of synaptic strength requires Ca(2+)/calmodulin (CaM)-dependent protein kinase II (CaMKII) and other kinases, whereas long-term depression (LTD) requires phosphatases. Here, we found that LTD also requires CaMKII and its phospho-T286-induced "autonomous" (Ca(2+)-independent) activity. However, whereas LTP is known to induce phosphorylation of the AMPA-type glutamate receptor (AMPAR) subunit GluA1 at S831, LTD instead induced CaMKII-mediated phosphorylation at S567, a site known to reduce synaptic GluA1 localization.

AKAP150-anchored calcineurin regulates synaptic plasticity by limiting synaptic incorporation of Ca2+-permeable AMPA receptors.

AMPA receptors (AMPARs) are tetrameric ion channels assembled from GluA1-GluA4 subunits that mediate the majority of fast excitatory synaptic transmission in the brain. In the hippocampus, most synaptic AMPARs are composed of GluA1/2 or GluA2/3 with the GluA2 subunit preventing Ca(2+) influx. However, a small number of Ca(2+)-permeable GluA1 homomeric receptors reside in extrasynaptic locations where they can be rapidly recruited to synapses during synaptic plasticity.

Commentary: How ethanol short-circuits the cerebellum-actions on Golgi cells in freely-moving animals.

This commentary discusses the important contributions of the article published in this journal by Huang and colleagues, titled, "Acute ethanol exposure increases firing and induces oscillations in cerebellar Golgi cells of freely moving rats." In this manuscript, Huang and colleagues present a number of interesting and important findings. While it has been shown previously that ethanol (EtOH) causes an increase in the firing of cerebellar Golgi cells in brain slice preparations and anesthetized animals, here the authors provide the first evidence that this action of EtOH occurs in vivo in freely moving, unanesthetized animals.

CaMKII "autonomy" is required for initiating but not for maintaining neuronal long-term information storage.

Ca(2+)/calmodulin (CaM)-dependent protein kinase II (CaMKII) "autonomy" (T286-autophosphorylation-induced Ca(2+)-independent activity) is required for long-term potentiation (LTP) and for learning and memory, as demonstrated by CaMKII T286A mutant mice. The >20-year-old hypothesis that CaMKII stimulation is required for LTP induction, while CaMKII autonomy is required for LTP maintenance was recently supported using the cell-penetrating fusion-peptide inhibitor antCN27. However, we demonstrate here that ant/penetratin fusion to CN27 compromised CaMKII-selectivity, by enhancing a previously unnoticed direct binding of CaM to ant/penetratin.

Modeling nonlinear phase noise in differentially phase-modulated optical communication systems.

Using an alternative approach for evaluating the Bit-Error Rate (BER), we present a numerical and experimental investigation of the performance of phase-modulated optical communication systems in the presence of nonlinear phase noise and dispersion. The numerical method is based on the well known Karhunen-Lo;eve expansion combined with a linearization technique of the Nonlinear Schr odinger Equation (NLSE) to account for the nonlinear interaction between signal and noise. Our numerical results show a good agreement with experiments.

Performance analysis of 20Gb/s RZ-DPSK non-slope matched transoceanic submarine links.

Direct computation of the bit-error rate (BER) and laboratory experiments are used to assess the performance of a non-slope matched transoceanic submarine transmission link operating at 20Gb/s channel rate and employing return-to-zero differential-phase shift keying (RZ-DPSK) signal modulation. Using this system as an example, we compare the accuracies of the existing theoretical approaches to the BER estimation for the RZ-DPSK format.

Differences in norepinephrine clearance in cerebellar slices from low-alcohol-sensitive and high-alcohol-sensitive rats.

High-alcohol-sensitive (HAS) and low-alcohol-sensitive (LAS) rats were bred for sensitivity and insensitivity, respectively, to the sedative/hypnotic effects of ethanol. These rats also display differential sensitivity to the depressant effects of locally applied ethanol on cerebellar Purkinje neurons in vivo. We have found that LAS animals exhibit a greater influence of endogenous beta-adrenergic activity on neuronal responses to gamma-aminobutyric acid (GABA) and ethanol than do HAS animals.