Two-way CSI-assisted AF relaying with HPA nonlinearity

In this paper, we investigate half-duplex two-way dual-hop channel state information (CSI)-assisted amplify-and-forward (AF) relaying in the presence of high-power amplifier (HPA) nonlinearity at relays. The expression for the end-to-end signal-to-noise ratio (SNR) is derived as per the modified system model by taking into account the interference caused by relaying scheme and HPA nonlinearity. The system performance of the considered relaying network is evaluated in terms of average symbol error probability (SEP) in Nakagami-$m$ fading channels, by making use of the moment-generating function (MGF) approach. Numerical results are provided and show the effects of several parameters, such as quadrature amplitude modulation (QAM) order, number of relays, HPA parameters, and Nakagami parameter, on performance.

Effects of the Allosteric Antagonist 1-(4-Chlorophenyl)-3-[3-(6-pyrrolidin-1-ylpyridin-2-yl)phenyl]urea (PSNCBAM-1) on CB1 Receptor Modulation in the Cerebellum

PSNCBAM-1 has recently been described as a cannabinoid CB1 receptor allosteric antagonist associated with hypophagic effects in vivo; however, PSNCBAM-1 effects on CB1 ligand-mediated modulation of neuronal excitability remain unknown. Here, we investigate PSNCBAM-1 actions on CB1 receptor-stimulated [35S]GTPγS binding in cerebellar membranes and on CB1 ligand modulation of presynaptic CB1 receptors at inhibitory interneurone-Purkinje cell (IN-PC) synapses in the cerebellum using whole-cell electrophysiology. PSNCBAM-1 caused non-competitive antagonism in [35S]GTPγS binding studies, with higher potency against the CB receptor agonist CP55940 than for WIN55,212-2 (WIN55). In electrophysiological studies, WIN55 and CP55940 reduced miniature inhibitory postsynaptic currents (mIPSCs) frequency, but not amplitude. PSNCBAM-1 application alone had no effect on mIPSCs; however, PSNCBAM-1 pre-treatment revealed agonist-dependent functional antagonism, abolishing CP55940-induced reductions in mIPSC frequency, but having no clear effect on WIN55 actions. The CB1 antagonist/inverse agonist AM251 increased mIPSC frequency beyond control, this effect was reversed by PSNCBAM-1. PSNCBAM-1 pre-treatment also attenuated AM251 effects. Thus, PSNCBAM-1 reduced CB1 receptor ligand functional efficacy in the cerebellum. The differential effect of PSNCBAM-1 on CP55940 versus WIN55 actions in [35S]GTPγS binding and electrophysiological studies and the attenuation of AM251 effects are consistent with the ligand-dependency associated with allosteric modulation. These data provide the first description of functional PSNCBAM-1 allosteric antagonist effects on neuronal excitability in the mammalian CNS. PSNCBAM-1 allosteric antagonism may provide viable therapeutic alternatives to orthosteric CB1 antagonists/inverse agonists in the treatment of CNS disease.

Inhibition of synaptic transmission and G protein modulation by synthetic CaV2.2 Ca2+ channel peptides

Abstract: Modulation of presynaptic voltage-dependent Ca+ channels is a major means of controlling neurotransmitter release. The CaV 2.2 Ca2+ channel subunit contains several inhibitory interaction sites for Gβγ subunits, including the amino terminal (NT) and I–II loop. The NT and I–II loop have also been proposed to undergo a G protein-gated inhibitory interaction, whilst the NT itself has also been proposed to suppress CaV 2 channel activity. Here, we investigate the effects of an amino terminal (CaV 2.2[45–55]) ‘NT peptide’ and a I–II loop alpha interaction domain (CaV 2.2[377–393]) ‘AID peptide’ on synaptic transmission, Ca2+ channel activity and G protein modulation in superior cervical ganglion neurones (SCGNs). Presynaptic injection of NT or AID peptide into SCGN synapses inhibited synaptic transmission and also attenuated noradrenaline-induced G protein modulation. In isolated SCGNs, NT and AID peptides reduced whole-cell Ca2+ current amplitude, modified voltage dependence of Ca2+ channel activation and attenuated noradrenaline-induced G protein modulation. Co-application of NT and AID peptide negated inhibitory actions. Together, these data favour direct peptide interaction with presynaptic Ca2+ channels, with effects on current amplitude and gating representing likely mechanisms responsible for inhibition of synaptic transmission. Mutations to residues reported as determinants of Ca2+ channel function within the NT peptide negated inhibitory effects on synaptic transmission, Ca2+ current amplitude and gating and G protein modulation. A mutation within the proposed QXXER motif for G protein modulation did not abolish inhibitory effects of the AID peptide. This study suggests that the CaV 2.2 amino terminal and I–II loop contribute molecular determinants for Ca2+ channel function; the data favour a direct interaction of peptides with Ca2+ channels to inhibit synaptic transmission and attenuate G protein modulation. Non-technical summary: Nerve cells (neurones) in the body communicate with each other by releasing chemicals (neurotransmitters) which act on proteins called receptors. An important group of receptors (called G protein coupled receptors, GPCRs) regulate the release of neurotransmitters by an action on the ion channels that let calcium into the cell. Here, we show for the first time that small peptides based on specific regions of calcium ion channels involved in GPCR signalling can themselves inhibit nerve cell communication. We show that these peptides act directly on calcium channels to make them more difficult to open and thus reduce calcium influx into native neurones. These peptides also reduce GPCR-mediated signalling. This work is important in increasing our knowledge about modulation of the calcium ion channel protein; such knowledge may help in the development of drugs to prevent signalling in pathways such as those involved in pain perception.

Modulation of visually evoked cortical fMRI responses by phase of ongoing occipital alpha oscillations

Using simultaneous electroencephalography as a measure of ongoing activity and functional magnetic resonance imaging (fMRI) as a measure of the stimulus-driven neural response, we examined whether the amplitude and phase of occipital alpha oscillations at the onset of a brief visual stimulus affects the amplitude of the visually evoked fMRI response. When accounting for intrinsic coupling of alpha amplitude and occipital fMRI signal by modeling and subtracting pseudo-trials, no significant effect of prestimulus alpha amplitude on the evoked fMRI response could be demonstrated. Regarding the effect of alpha phase, we found that stimuli arriving at the peak of the alpha cycle yielded a lower blood oxygenation level-dependent (BOLD) fMRI response in early visual cortex (V1/V2) than stimuli presented at the trough of the cycle. Our results therefore show that phase of occipital alpha oscillations impacts the overall strength of a visually evoked response, as indexed by the BOLD signal. This observation complements existing evidence that alpha oscillations reflect periodic variations in cortical excitability and suggests that the phase of oscillations in postsynaptic potentials can serve as a mechanism of gain control for incoming neural activity. Finally, our findings provide a putative neural basis for observations of alpha phase dependence of visual perceptual performance.

Ultralow-frequency modulation of whistler-mode wave growth

Measurements from ground-based magnetometers and riometers at auroral latitudes have demonstrated that energetic (~30-300keV) electron precipitation can be modulated in the presence of magnetic field oscillations at ultra-low frequencies. It has previously been proposed that an ultra-low frequency (ULF) wave would modulate field and plasma properties near the equatorial plane, thus modifying the growth rates of whistler-mode waves. In turn, the resulting whistler-mode waves would mediate the pitch-angle scattering of electrons resulting in ionospheric precipitation. In this paper, we investigate this hypothesis by quantifying the changes to the linear growth rate expected due to a slow change in the local magnetic field strength for parameters typical of the equatorial region around 6.6RE radial distance. To constrain our study, we determine the largest possible ULF wave amplitudes from measurements of the magnetic field at geosynchronous orbit. Using nearly ten years of observations from two satellites, we demonstrate that the variation in magnetic field strength due to oscillations at 2mHz does not exceed ±10% of the background field. Modifications to the plasma density and temperature anisotropy are estimated using idealised models. For low temperature anisotropy, there is little change in the whistler-mode growth rates even for the largest ULF wave amplitude. Only for large temperature anisotropies can whistler-mode growth rates be modulated sufficiently to account for the changes in electron precipitation measured by riometers at auroral latitudes.

Modulation of equatorial Pacific westerly/easterly wind events by the Madden-Julian oscillation and convectively-coupled Rossby waves

Synoptic wind events in the equatorial Pacific strongly influence the El Niño/Southern Oscillation (ENSO) evolution. This paper characterizes the spatio-temporal distribution of Easterly (EWEs) and Westerly Wind Events (WWEs) and quantifies their relationship with intraseasonal and interannual large-scale climate variability. We unambiguously demonstrate that the Madden–Julian Oscillation (MJO) and Convectively-coupled Rossby Waves (CRW) modulate both WWEs and EWEs occurrence probability. 86 % of WWEs occur within convective MJO and/or CRW phases and 83 % of EWEs occur within the suppressed phase of MJO and/or CRW. 41 % of WWEs and 26 % of EWEs are in particular associated with the combined occurrence of a CRW/MJO, far more than what would be expected from a random distribution (3 %). Wind events embedded within MJO phases also have a stronger impact on the ocean, due to a tendency to have a larger amplitude, zonal extent and longer duration. These findings are robust irrespective of the wind events and MJO/CRW detection methods. While WWEs and EWEs behave rather symmetrically with respect to MJO/CRW activity, the impact of ENSO on wind events is asymmetrical. The WWEs occurrence probability indeed increases when the warm pool is displaced eastward during El Niño events, an increase that can partly be related to interannual modulation of the MJO/CRW activity in the western Pacific. On the other hand, the EWEs modulation by ENSO is less robust, and strongly depends on the wind event detection method. The consequences of these results for ENSO predictability are discussed.