ASCA Observation of the Crab-Like Supernova Remnant 3C58

We present here the X-ray observation of a Crab-like supernova remnant (SNR) 3C58 with ASCA. We find that the integrated energy spectrum over the nebula is consistent with previous results, showing a power-law spectrum with the photon index $\gamma = 2.2-2.4$ modified by interstellar absorption of about $(3-4)\times 10^{21}{\rm cm^{-2}}$. Inclusion of a blackbody component which is attributable to the central compact source significantly improves the spectral fit. Stringent upper limits for any line emitting thin hot plasma are established. We find for the first time that the nebular spectrum is harder in the central part of the SNR, becoming softer toward the periphery, while the absorption column is uniform across the nebula. Correspondingly, the nebular size decreases with increasing photon energy which is a steeper function of radius than that of the Crab nebula. The results are compared with synchrotron energy loss models and the nature of the putative pulsar is discussed. Timing analysis was performed to search for pulsed X-ray emission from the central compact source. No significant pulsations are observed, and we present the upper limit for the pulsed fraction.Comment: 27 pages, 7 figures, to appear in PAS

Discovery of the compact X-ray source inside the Cygnus Loop

We detected an X-ray compact source inside the Cygnus Loop during the observation project of the whole Cygnus Loop with the ASCA GIS. The source intensity is 0.11 c s$^{-1}$ for GIS and 0.15 c s$^{-1}$ for SIS, which is the strongest in the ASCA band. The X-ray spectra are well fitted by a power law spectrum of a photon index of \error{-2.1}{0.1} with neutral H column of (\error{3.1}{0.6})${\rm \times 10^{21} cm^{-2}}$. Taking into account the interstellar absorption feature, this source is X-ray bright mainly above 1 keV suggesting either an AGN or a rotating neutron star. So far, we did not detect intensity variation nor coherent pulsation mainly due to the limited observation time. There are several optical bright stellar objects within the error region of the X-ray image. We carried out the optical spectroscopy for the brightest source (V=+12.6) and found it to be a G star. The follow up deep observation both in optical and in X-ray wavelengths are strongly required.Comment: Accepted for Publications of the Astronomical Society of Japan 17 pages, 3 figur

ASCA Observation of the Nearest Gravitational Lensing Cluster Candidate -- A 3408

We observed the nearest gravitational lensing cluster candidate, A 3408 (${\it z}=0.042$), with ASCA. The projected mass profile of A 3408 was determined from the ICM temperature and the $\beta$-model parameters obtained with ASCA, assuming that the hot gas is spherically symmetric and in hydrostatic equilibrium. The projected mass within an arc radius, $r_{\rm arc}$, of 110 kpc is M(r_{\rm arc})=1.2^{+0.8}_{-0.4} \times10^{13} \MO. This is 18 -- 45% of the mass previously derived from a lensing analysis by Campusano et al. (1998, AAA 069.160.189) without any X-ray information. The primary cause of this discrepancy is in their assumption that the center of the cluster potential coincides with the position of the brightest cluster galaxy (BCG), while we reveal the BCG position to be 60$''$ outside of the X-ray center. We further calculated a model for the source galaxy position and the gravitational potential that can reproduce both the X-ray data and the arc image. In this model, the magnification factor of the lens for the source galaxy was evaluated to be ${\Delta}m=$ 0.07$\pm$0.03 mag; i.e., the source galaxy is slightly magnified by the lens cluster A 3408.Comment: 13 pages, 6 figures, to appear in PASJ vol. 5

A biophysical model of endocannabinoid-mediated short term depression in hippocampal inhibition

Memories are believed to be represented in the synaptic pathways of vastly interconnected networks of neurons. The plasticity of synapses, that is, their strengthening and weakening depending on neuronal activity, is believed to be the basis of learning and establishing memories. An increasing number of studies indicate that endocannabinoids have a widespread action on brain function through modulation of synap–tic transmission and plasticity. Recent experimental studies have characterised the role of endocannabinoids in mediating both short- and long-term synaptic plasticity in various brain regions including the hippocampus, a brain region strongly associated with cognitive functions, such as learning and memory. Here, we present a biophysically plausible model of cannabinoid retrograde signalling at the synaptic level and investigate how this signalling mediates depolarisation induced suppression of inhibition (DSI), a prominent form of shortterm synaptic depression in inhibitory transmission in hippocampus. The model successfully captures many of the key characteristics of DSI in the hippocampus, as observed experimentally, with a minimal yet sufficient mathematical description of the major signalling molecules and cascades involved. More specifically, this model serves as a framework to test hypotheses on the factors determining the variability of DSI and investigate under which conditions it can be evoked. The model reveals the frequency and duration bands in which the post-synaptic cell can be sufficiently stimulated to elicit DSI. Moreover, the model provides key insights on how the state of the inhibitory cell modulates DSI according to its firing rate and relative timing to the post-synaptic activation. Thus, it provides concrete suggestions to further investigate experimentally how DSI modulates and is modulated by neuronal activity in the brain. Importantly, this model serves as a stepping stone for future deciphering of the role of endocannabinoids in synaptic transmission as a feedback mechanism both at synaptic and network level

Cannabinoid-mediated short-term plasticity in hippocampus

Endocannabinoids modulate both excitatory and inhibitory neurotransmission in hippocampus via activation of pre-synaptic cannabinoid receptors. Here, we present a model for cannabinoid mediated short-term depression of excitation (DSE) based on our recently developed model for the equivalent phenomenon of suppressing inhibition (DSI). Furthermore, we derive a simplified formulation of the calcium-mediated endocannabinoid synthesis that underlies short-term modulation of neurotransmission in hippocampus. The simplified model describes cannabinoid-mediated short-term modulation of both hippocampal inhibition and excitation and is ideally suited for large network studies. Moreover, the implementation of the simplified DSI/DSE model provides predictions on how both phenomena are modulated by the magnitude of the pre-synaptic cell's activity. In addition we demonstrate the role of DSE in shaping the post-synaptic cell's firing behaviour qualitatively and quantitatively in dependence on eCB availability and the pre-synaptic cell's activity. Finally, we explore under which conditions the combination of DSI and DSE can temporarily shift the fine balance between excitation and inhibition. This highlights a mechanism by which eCBs might act in a neuro-protective manner during high neural activity

Increased vesicle fusion competence underlies long-term potentiation at hippocampal mossy fiber synapses

Presynaptic long-term potentiation (LTP) is thought to play an important role in learning and memory. However, the underlying mechanism remains elusive because of the difficulty of direct recording during LTP. Hippocampal mossy fiber synapses exhibit pronounced LTP of transmitter release after tetanic stimulation and have been used as a model of presynaptic LTP. Here, we induced LTP by optogenetic tools and applied direct presynaptic patch-clamp recordings. The action potential waveform and evoked presynaptic Ca2+ currents remained unchanged after LTP induction. Membrane capacitance measurements suggested higher release probability of synaptic vesicles without changing the number of release-ready vesicles after LTP induction. Synaptic vesicle replenishment was also enhanced. Furthermore, stimulated emission depletion microscopy suggested an increase in the numbers of Munc13-1 and RIM1 molecules within active zones. We propose that dynamic changes in the active zone components may be relevant for the increased fusion competence and synaptic vesicle replenishment during LTP

ホスホリパーゼCβはCa[2+]依存性を介して逆行性内因性カンナビノイドシグナルの発生に際し同期性検出器として働く

取得学位 : 博士（医学）, 学位授与番号 : 医博甲第1685号, 学位授与年月日 : 平成17年3月22日, 学位授与大学 : 金沢大

Ca2+-assisted receptor-driven endocannabinoid release: mechanisms that associate presynaptic and postsynaptic activities

金沢大学大学院医学系研究科機能障害学Endogenous cannabinoids (endocannabinoids) serve as retrograde messengers at synapses in various regions of the brain. They are released from postsynaptic neurons and cause transient and long-lasting reduction of neurotransmitter release through activation of presynaptic cannabinoid receptors. Endocannabinoid release is induced either by increased postsynaptic Ca2+ levels or by activation of Gq/11-coupled receptors. When these two stimuli coincide, endocannabinoid release is markedly enhanced, which is attributed to the Ca2+ dependency of phospholipase Cβ (PLCβ). This Ca2+-assisted receptor-driven endocannabinoid release is suggested to participate in various forms of synaptic plasticity, including short-term associative plasticity in the cerebellum and spike-timing-dependent long-term depression in the somatosensory cortex. In these forms of plasticity, PLCβ seems to function as a coincident detector of presynaptic and postsynaptic activities. © 2007 Elsevier Ltd. All rights reserved

Presynaptic monoacylglycerol lipase activity determines basal endocannabinoid tone and terminates retrograde endocannabinoid signaling in the hippocampus

金沢大学大学院医学系研究科機能障害学Endocannabinoids function as retrograde messengers and modulate synaptic transmission through presynaptic cannabinoid CB1 receptors. The magnitude and time course of endocannabinoid signaling are thought to depend on the balance between the production and degradation of endocannabinoids. The major endocannabinoid 2-arachidonoylglycerol (2-AG) is hydrolyzed by monoacylglycerol lipase (MGL), which is shown to be localized at axon terminals. In the present study, we investigated how MGL regulates endocannabinoid signaling and influences synaptic transmission in the hippocampus. We found that MGL inhibitors, methyl arachidonoyl fluorophosphonate and arachidonoyl trifluoromethylketone, caused a gradual suppression of cannabinoid-sensitive IPSCs in cultured hippocampal neurons. This suppression was reversed by blocking CB1 receptors and was attenuated by inhibiting 2-AG synthesis, indicating that MGL scavenges constitutively released 2-AG. We also found that the MGL inhibitors significantly prolonged the suppression of both IPSCs and EPSCs induced by exogenous 2-AG and depolarization-induced suppression of inhibition/excitation, a phenomenon known to be mediated by retrograde endocannabinoid signaling. In contrast, inhibitors of other endocannabinoid hydrolyzing enzymes, fatty acid amide hydrolase and cyclooxygenase-2, had no effect on the 2-AG-induced IPSC suppression. These results strongly suggest that presynaptic MGL not only hydrolyzes 2-AG released from activated postsynaptic neurons but also contributes to degradation of constitutively produced 2-AG and prevention of its accumulation around presynaptic terminals. Thus, the MGL activity determines basal endocannabinoid tone and terminates retrograde endocannabinoid signaling in the hippocampus. Copyright © 2007 Society for Neuroscience

Hypothalamic Supramammillary Control of Cognition and Motivation.

The supramammillary nucleus (SuM) is a small region in the ventromedial posterior hypothalamus. The SuM has been relatively understudied with much of the prior focus being on its connection with septo-hippocampal circuitry. Thus, most studies conducted until the 21st century examined its role in hippocampal processes, such as theta rhythm and learning/memory. In recent years, the SuM has been "rediscovered" as a crucial hub for several behavioral and cognitive processes, including reward-seeking, exploration, and social memory. Additionally, it has been shown to play significant roles in hippocampal plasticity and adult neurogenesis. This review highlights findings from recent studies using cutting-edge systems neuroscience tools that have shed light on these fascinating roles for the SuM