Desynchronization of pathological low-frequency brain activity by the hypnotic drug zolpidem.

Reports of the beneficial effects of the hypnotic imidazopyridine, zolpidem, described in persistent vegetative state^1, 2^ have been replicated recently in brain-injured and cognitively impaired patients^3-7^. Previous single photon emission computed tomography (SPECT) studies have suggested that sub-sedative doses of zolpidem increased regional cerebral perfusion in affected areas^5, 8^, implying enhanced neuronal metabolic activity; which has led to speculation that zolpidem 'reawakens' functionally dormant cortex. However, a neuronal mechanism by which this hypnotic drug affords benefits to brain injured patients has yet to be demonstrated. Here, we report the action of sub-sedative doses of zolpidem on neuronal network oscillatory activity in human brain, measured using pharmaco-magnetoencephalography (pharmaco-MEG). Study participant JP suffered a stroke in 1996, causing major damage to the left hemisphere that impaired aspects of both motor and cognitive function. Pharmaco-MEG analyses revealed robust and persistent pathological theta (4-10Hz) and beta (15-30Hz) oscillations within the lesion penumbra and surrounding cortex. Administration of zolpidem (5mg) reduced the power of pathological theta and beta oscillations in all regions of the lesioned hemisphere. This desynchronizing effect correlated well with zolpidem uptake (occurring approximately 40 minutes after acute administration) and was coincident with marked improvements in cognitive and motor function. Control experiments revealed no effect of placebo, while a structurally unrelated hypnotic, zopiclone, administered at a comparable dose (3.5mg) elicited widespread increases in cortical oscillatory power in the beta (15-30Hz) band without functional improvement. These results suggest that in JP, specific motor and cognitive impairments are related to increased low-frequency oscillatory neuronal network activity. Zolpidem is unique amongst hypnotic drugs in its ability to desynchronize such pathological low-frequency activity, thereby restoring cognitive function

Frequency selectivity and dopamine-dependence of plasticity at glutamatergic synapses in the subthalamic nucleus

In Parkinson's disease, subthalamic nucleus (STN) neurons burst fire with increased periodicity and synchrony. This may entail abnormal release of glutamate, the major source of which in STN is cortical afferents. Indeed, the cortico-subthalamic pathway is implicated in the emergence of excessive oscillations, which are reduced, as are symptoms, by dopamine-replacement therapy or deep brain stimulation (DBS) targeted to STN. Here we hypothesize that glutamatergic synapses in the STN may be differentially modulated by low-frequency stimulation (LFS) and high-frequency stimulation (HFS), the latter mimicking deep brain stimulation. Recordings of evoked and spontaneous excitatory post synaptic currents (EPSCs) were made from STN neurons in brain slices obtained from dopamine-intact and chronically dopamine-depleted adult rats. HFS had no significant effect on evoked (e) EPSC amplitude in dopamine-intact slices (104.4±8.0%) but depressed eEPSCs in dopamine-depleted slices (67.8±6.2%). Conversely, LFS potentiated eEPSCs in dopamine-intact slices (126.4±8.1%) but not in dopamine-depleted slices (106.7±10.0%). Analyses of paired-pulse ratio, coefficient of variation, and spontaneous EPSCs suggest that the depression and potentiation have a presynaptic locus of expression. These results indicate that the synaptic efficacy in dopamine-intact tissue is enhanced by LFS. Furthermore, the synaptic efficacy in dopamine-depleted tissue is depressed by HFS. Therefore the therapeutic effects of DBS in Parkinson's disease appear mediated, in part, by glutamatergic cortico-subthalamic synaptic depression and implicate dopamine-dependent increases in the weight of glutamate synapses, which would facilitate the transfer of pathological oscillations from the cortex

Revealing Short-period Exoplanets and Brown Dwarfs in the Galactic Bulge using the Microlensing Xallarap Effect with the \textit{Nancy Grace Roman Space Telescope}

The \textit{Nancy Grace Roman Space Telescope} (\textit{ Roman}) will provide an enormous number of microlensing light curves with much better photometric precisions than ongoing ground-based observations. Such light curves will enable us to observe high-order microlensing effects which have been previously difficult to detect. In this paper, we investigate \textit{Roman}'s potential to detect and characterize short-period planets and brown dwarfs (BDs) in source systems using the orbital motion of source stars, the so-called xallarap effect. We analytically estimate the measurement uncertainties of xallarap parameters using the Fisher matrix analysis. We show that the \textit{Roman} Galactic Exoplanet Survey (RGES) can detect warm Jupiters with masses down to 0.5 $M_{\rm Jup}$ and orbital period of 30 days via the xallarap effect. Assuming a planetary frequency function from \citet{Cumming+2008}, we find \textit{Roman} will detect $\sim10$ hot and warm Jupiters and $\sim30$ close-in BDs around microlensed source stars during the microlensing survey. These detections are likely to be accompanied by the measurements of the companion's masses and orbital elements, which will aid in the study of the physical properties for close-in planet and BD populations in the Galactic bulge.Comment: Accepted for publication in The Astronomical Journa

The role of GABAergic modulation in motor function related neuronal network activity

At rest, the primary motor cortex (M1) exhibits spontaneous neuronal network oscillations in the beta (15–30 Hz) frequency range, mediated by inhibitory interneuron drive via GABA-A receptors. However, questions remain regarding the neuropharmacological basis of movement related oscillatory phenomena, such as movement related beta desynchronisation (MRBD), post-movement beta rebound (PMBR) and movement related gamma synchronisation (MRGS). To address this, we used magnetoencephalography (MEG) to study the movement related oscillatory changes in M1 cortex of eight healthy participants, following administration of the GABA-A modulator diazepam. Results demonstrate that, contrary to initial hypotheses, neither MRGS nor PMBR appear to be GABA-A dependent, whilst the MRBD is facilitated by increased GABAergic drive. These data demonstrate that while movement-related beta changes appear to be dependent upon spontaneous beta oscillations, they occur independently of one other. Crucially, MRBD is a GABA-A mediated process, offering a possible mechanism by which motor function may be modulated. However, in contrast, the transient increase in synchronous power observed in PMBR and MRGS appears to be generated by a non-GABA-A receptor mediated process; the elucidation of which may offer important insights into motor processes

東シナ海の流れ藻に蝟集する稚魚の摂餌生態と海洋環境

Many commercially important fishes associate with drifting seaweeds in their juvenile stage, however, the ecological significance of drifting seaweeds for juvenile fishes is still unclear. We postulated that the following two hypotheses may be applicable for juvenile fishes associate with drifting seaweeds, the “concentration of food supply” hypothesis: juvenile fishes are attracted by phytal animals on the drifting seaweeds and the “indicator-log” hypothesis: fish use accumulations of drifting seaweed as an indicator of productive areas (e.g. frontal areas) for food. We investigated the frontal areas, zooplankton abundance around the drifting seaweed, and the food availability of fish juveniles associated with drifting seaweed accumulations in the East China Sea in 2012 and 2013. A total of 14 drifting seaweed mass and 22 species (n = 408) of fish juveniles were collected. We found that 49.7 - 99.7 % of the individual fed on planktonic food and the feeding incidence on phytal animals was less than 50 %. Although drifting seaweeds were aggregated around the frontal areas of surface currents, the zooplankton abundance was not significantly different between these frontal areas and other areas. Our findings indicate that ecological significance of drifting seaweeds as feeding habit is relatively low for juvenile fishes associated with drifting seaweeds.流れ藻には多くの水産上重要種の稚魚が付随するが，流れ藻の稚魚にとっての生態学的意義は明らかにされていない。筆者らは次の2仮説のいずれかが流れ藻付随稚魚に当てはまると考え，“concentration of food supply hypothesis”（流れ藻葉上生物を摂餌するため）と“indicator log hypothesis”（流れ藻をフロント域のような餌豊度の高い海域の目印とするため）を検証するため，2012年と2013年に東シナ海の流れ藻周辺の海洋環境，フロント域，動物プランクトン豊度，流れ藻付随稚魚の摂餌個体率を調べた。流れ藻は表層流の収束帯に集積されていたが，収束帯のプランクトン豊度は高くなかった。合計14個の流れ藻を採集し，合計22種（408尾）の稚魚の胃内容物を調査した結果，稚魚の49.7 - 99.7 %の個体はプランクトンを選択的に摂餌していたが，葉上生物の摂餌個体率は高くなかった（50 %未満）。以上の結果から流れ藻の稚魚にとっての生態学的意義は摂餌場でないことが示唆された

Candidate Brown-dwarf Microlensing Events with Very Short Timescales and Small Angular Einstein Radii

Short-timescale microlensing events are likely to be produced by substellar brown dwarfs (BDs), but it is difficult to securely identify BD lenses based on only event timescales t_E because short-timescale events can also be produced by stellar lenses with high relative lens-source proper motions. In this paper, we report three strong candidate BD-lens events found from the search for lensing events not only with short timescales (t_E ≲ 6 days) but also with very small angular Einstein radii (θ_E ≲ 0.05 mas) among the events that have been found in the 2016–2019 observing seasons. These events include MOA-2017-BLG-147, MOA-2017-BLG-241, and MOA-2019-BLG-256, in which the first two events are produced by single lenses and the last event is produced by a binary lens. From the Monte Carlo simulations of Galactic events conducted with the combined t_E and θ_E constraint, it is estimated that the lens masses of the individual events are 0.051^(+0.100)_(−0.027) M⊙, 0.044^(+0.090)_(−0.023) M⊙, and 0.046^(+0.067)_(−0.023) M⊙/0.038^(+0.056)_(−0.019) M⊙ and the probability of the lens mass smaller than the lower limit of stars is ~80% for all events. We point out that routine lens mass measurements of short-timescale lensing events require survey-mode space-based observations

Spike firing and IPSPs in layer V pyramidal neurons during beta oscillations in rat primary motor cortex (M1) in vitro

Beta frequency oscillations (10-35 Hz) in motor regions of cerebral cortex play an important role in stabilising and suppressing unwanted movements, and become intensified during the pathological akinesia of Parkinson's Disease. We have used a cortical slice preparation of rat brain, combined with concurrent intracellular and field recordings from the primary motor cortex (M1), to explore the cellular basis of the persistent beta frequency (27-30 Hz) oscillations manifest in local field potentials (LFP) in layers II and V of M1 produced by continuous perfusion of kainic acid (100 nM) and carbachol (5 µM). Spontaneous depolarizing GABA-ergic IPSPs in layer V cells, intracellularly dialyzed with KCl and IEM1460 (to block glutamatergic EPSCs), were recorded at -80 mV. IPSPs showed a highly significant (P< 0.01) beta frequency component, which was highly significantly coherent with both the Layer II and V LFP oscillation (which were in antiphase to each other). Both IPSPs and the LFP beta oscillations were abolished by the GABAA antagonist bicuculline. Layer V cells at rest fired spontaneous action potentials at sub-beta frequencies (mean of 7.1+1.2 Hz; n = 27) which were phase-locked to the layer V LFP beta oscillation, preceding the peak of the LFP beta oscillation by some 20 ms. We propose that M1 beta oscillations, in common with other oscillations in other brain regions, can arise from synchronous hyperpolarization of pyramidal cells driven by synaptic inputs from a GABA-ergic interneuronal network (or networks) entrained by recurrent excitation derived from pyramidal cells. This mechanism plays an important role in both the physiology and pathophysiology of control of voluntary movement generation

A Gas Giant Planet in the OGLE-2006-BLG-284L Stellar Binary System

We present the analysis of microlensing event OGLE-2006-BLG-284, which has a lens system that consists of two stars and a gas giant planet with a mass ratio of $q_p = (1.26\pm 0.19) \times 10^{-3}$ to the primary. The mass ratio of the two stars is $q_s = 0.289\pm 0.011$, and their projected separation is $s_s = 2.1\pm 0.7\,$AU, while the projected separation of the planet from the primary is $s_p = 2.2\pm 0.8\,$AU. For this lens system to have stable orbits, the three-dimensional separation of either the primary and secondary stars or the planet and primary star must be much larger than that these projected separations. Since we do not know which is the case, the system could include either a circumbinary or a circumstellar planet. Because there is no measurement of the microlensing parallax effect or lens system brightness, we can only make a rough Bayesian estimate of the lens system masses and brightness. We find host star and planet masses of $M_{L1} = 0.35^{+0.30}_{-0.20}\,M_\odot$, $M_{L2} = 0.10^{+0.09}_{-0.06}\,M_\odot$, and $m_p = 144^{+126}_{-82}\,M_\oplus$, and the $K$-band magnitude of the combined brightness of the host stars is $K_L = 19.7^{+0.7}_{-1.0}$. The separation between the lens and source system will be $\sim 90\,$mas in mid-2020, so it should be possible to detect the host system with follow-up adaptive optics or Hubble Space Telescope observations