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Chronic Forced and Free Exercise on Cocaine Place Conditioning and Glutamatergic Synaptic Plasticity in the VTA
Get PDFExercise may be useful in preventing substance use disorders and addiction. It is well known that chronic exercise, both forced and voluntary, decreases addiction vulnerability in rodent models and likely in humans. However, the mechanism by which chronic exercise accomplishes this has not been fully evaluated. Here, a conditioned place preference (CPP) paradigm was used to measure the learning of cocaine-associated environmental cues in two groups of rats following a period of both forced and free running. It is shown that rats subjected to chronic forced running displayed no significant deviation in learning of contextual cues paired with cocaine through CPP. On the other hand, rats subjected to chronic free running displayed a notable decrease in acquisition of cocaine-CPP. To investigate the mechanism by which chronic exercise affects cocaine-CPP, we will conduct future electrophysiological studies in the ventral tegmental area (VTA), an area that has been widely implicated in the natural reward circuitry of the brain. The VTA and its role in addiction has been studied extensively by the Morikawa Lab, with one previous study finding that repeated social defeat stress enhances glutamatergic synaptic plasticity in the VTA and cocaine-CPP. Essentially, we expect to observe a decrease in long-term potentiation (LTP) of NMDA-mediated glutamatergic synaptic plasticity in the VTA and consequently, a decrease in cocaine-CPP following both chronic forced and free exercise. If observed, our findings will suggest that decreased plasticity of glutamatergic transmission may be responsible for decreased addiction vulnerability through chronic exercise.Neuroscienc
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Burst timing-dependent plasticity of NMDA receptor-mediated transmission in midbrain dopamine neurons : a putative cellular substrate for reward learning
Get PDFtextThe neurotransmitter dopamine (DA) represents a neural substrate for positive
motivation as its spatiotemporal distribution across the brain is responsible for goaldirected
behavior and learning reward associations. The critical determinant of DA
release throughout the brain is the firing pattern of DA-producing neurons. Synchronized
bursts of spikes can be triggered by sensory stimuli in these neurons, evoking phasic
release of DA in target brain areas to drive reward-based reinforcement learning and
behavior. These bursts are generated by NMDA-type glutamate receptors (NMDARs).
This dissertation reports a novel form of long-term potentiation (LTP) of NMDARmediated
excitatory transmission at DA neurons as a putative cellular substrate for
changes in DA neuron firing during reward learning.
Patch-clamp electrophysiological recording from DA neurons in acute brain slices
from young adult rats demonstrated that synaptic NMDARs exhibit LTP in an associative manner, requiring coordinated pre- and postsynaptic burst firing. Ca2+ signals produced
by postsynaptic burst firing needed to be amplified by preceding metabotropic
neurotransmitter inputs to effectively drive plasticity. Activation of NMDARs
themselves was also necessary. These two coincidence detectors governed the timingdependence
of NMDAR plasticity in a manner analogous to the timing rule for cuereward
learning paradigms in behaving animals. Further mechanistic study revealed that
PKA, but not PKC, activity gated LTP induction by regulating the magnitude of Ca2+
signal amplification via the inositol 1,4,5-triphospate (IP3) receptor and release of Ca2+
from intracellular stores. Plasticity of NMDARs was input specific and appeared to be
expressed postsynaptically, but was not associated with a change in NMDAR subunit
stoichiometry. LTP of NDMARs was DA-independent, and was specific for NMDARs:
the same induction protocol produced long-term depression of AMPA receptors.
NMDARs that had undergone LTP could be depotentiated in a spike-conditional manner,
consistent with active unlearning. Finally, repeated, in vivo amphetamine experience
dramatically increased facilitation of spike-evoked Ca2+ signals, which in turn drove
enhanced plasticity.
NMDAR plasticity thus represents a potential neural substrate for conditioned DA
neuron burst responses to environmental stimuli acquired during reward-based learning
as well a novel therapeutic target for intervention-based therapy of addictive disorders.Institute for Neuroscienc
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Recurrent inhibitory network among cholinergic inerneurons of the striatum
Get PDFtextThe striatum is the initial input nuclei of the basal ganglia, and it serves as an integral processing center for action selection and sensorimotor learning. Glutamatergic projections from the cortex and thalamus converge with dense dopaminergic axons from the midbrain to provide the primary inputs to the striatum. Striatal output is then relayed to downstream basal ganglia nuclei by GABAergic medium – sized spiny neurons, which comprise at least 95% of the population of neurons in the striatum. The remaining population of local circuit neurons is dedicated to regulating the activity of spiny projection neurons, and although spiny neurons form a weak lateral inhibitory network among themselves via local axon collaterals, feedforward modulation exerts more powerful control over spiny neuron excitability. Of the striatal interneurons, only one class is not GABAergic. These neurons are cholinergic and correspond to the tonically active neurons (TANs) recorded in vivo, which respond to specific environmental stimuli with a transient depression, or pause, of tonic firing. Striatal cholinergic interneurons account for less than 2 % of the striatal neuronal population, yet their axons form an extensive and complex network that permeates the entire striatum and significantly shapes striatal output by acting at numerous targets via varied receptor types. Indeed, the persistent level of ambient striatal acetylcholine as well as changes to that basal acetylcholine level underlie the major mechanisms of cholinergic signaling in the striatum, however regulation of this system by the local striatal microcircuitry is not well understood. This dissertation finds that activation of intrastriatal cholinergic fibers elicits polysynaptic GABAA inhibitory postsynaptic currents (IPSCs) in cholinergic interneurons recorded in brain slices. Excitation of striatal GABAergic neurons via nicotinic acetylcholine receptors (nAChRs) mediates this polysynaptic inhibition in a manner independent of dopamine. Moreover, activation of a single cholinergic interneuron is capable of eliciting polysynaptic GABAA IPSCs onto itself and nearby cholinergic interneurons. These findings provide an important insight into the striatal microcircuitry controlling cholinergic neuron excitability.Cellular and Molecular Biolog
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Differential regulation of Ca²⁺ signals in dopamine neurons: a potential mechanism for neuroadaptive changes underlying drug addiction
Get PDFtextA key adaptive change in the brain reward circuitry during the
development of drug addiction is augmented dopamine (DA) release in response
to addictive drugs. Potentiated glutamatergic synaptic transmission onto
midbrain DA neurons has been suggested to be one of the cellular mechanisms
mediating this change. Intracellular Ca2+ ([Ca2+
]i) rise associated with
postsynaptic bursts of action potentials (APs) and metabotropic glutamate
receptor (mGluR) activation has been implicated in the induction of long-term
potentiation (LTP) and long-term depression (LTD), respectively, of glutamate
transmission in DA neurons. In this dissertation, we found a unique mechanism
that differentially regulates these two opposing Ca2+ signals. We performed
patch-clamp recordings from DA neurons in acutely cut brain slices, and showed
that tonic activation of metabotropic neurotransmitter receptors (such as mGluRs,
α1 adrenergic receptors, and muscarinic acetylcholine receptors), attained by
weak, sustained (~1 sec) synaptic stimulation or bath application of selective
agonists, augmented AP-induced Ca2+ transients while inhibiting Ca2+ signals
elicited by strong, transient activation of mGluRs. This differential regulation is
mediated by increased intracellular inositol 1,4,5-triphosphate (IP3) levels, since it
was blocked by IP3 receptor antagonist heparin and reproduced by photolytic
application of IP3. We further showed that AP-induced Ca2+ transients were
regulated by the firing context of dopamine neurons. Evoking APs repetitively at
low frequency (2 Hz) mimicking the basal firing of DA neurons caused
inactivation of IP3 receptors and inhibited AP-induced Ca2+ transients. IP3
facilitation of single AP-induced Ca2+ signals was completely abolished during
the AP train, while facilitation of Ca2+ signals triggered by bursts of APs (5 spikes
at 20 Hz) was attenuated by less than half, indicating that increased IP3 level
selectively amplifies Ca2+ signals associated with bursts but not single APs in a
tonicly firing neuron. Finally, we obtained evidence suggesting that
psychostimulant amphetamine may augment burst-induced Ca2+ signals via both
depression of basal firing and production of IP3. We propose that the differential
Ca2+ regulation mechanisms described in this dissertation may induce a shift in
the balance of plasticity toward burst-dependent LTP in DA neurons and may
contribute to the development of drug addiction.Institute for Neuroscienc
Velocity and Q structure of waves for soil sediments at Heijo in the northern part of Nara basin inferred from seismic observation with vertical array
No full text奈良盆地北部の平城宮跡地で実施されている鉛直アレー地震観測では, 基盤境界生成SP変換波と地表面からの反射S波が明瞭に記録される。地表/地中スペクトル比は, 概ね奇数倍の周波数列にシャープなピークを有する。また, 水平動/上下動スペクトル比には盆地の基盤構造に由来する山谷が顕著に現れる。これらのデータを基に, ‐深さ約600mの基盤岩までの地盤のS波速度とQ値のモデル化を行った。S波のQ値は, 周波数の1乗に, またs波速度の2‐3乗に依存していた。構造モデルから推定される地盤の固有周期は基本モードで約3秒, 増幅率は広い周波数範囲で約4倍であった。To elucidate subsurface structure and ground vibration characteristics at Heijo, Nara basin, where 'Daigokuden', government office in the Nara era is planned to be restored to its original state, seismic observation has been carried out at GL Om, -20m, -42m and - lOOm in a borehole. The depth to bedrock is known to be about 600m from nearby deep boreholes. It is notable that, almost all the seismograms showremarkable SP phases generated at the soil-bedrock boundary and down-going S-waves reflected at groundsurface. We made spectral analyses of S wave parts including preceding SP phases; surface-to-subsurface spectral ratios (Ho/H-d) and horizontal-to-vertical spectral ratio (H/V). Ho/l-l-d shows sharp peaks at oddmultiple frequencies. Remarkable peaks and troughs of fundamental mode in H/V are observed, even though incident angle of SV phases at bedrock exceed the critical angle (arcsin (Vs/Vp); V in bedrock). We estimated S wave velocity and Q structure using Haskell method. As a result, it was found that, Qs depends on 1stpower of frequency and 2nd to 3rd power of Vs, fundamental natural-period of ground is 3s, andsoil-amplification is about 4 for 1-20Hz.奈良盆地北部の平城宮跡地で実施されている鉛直アレー地震観測では,基盤境界生成SP変換波と地表面からの反射S波が明瞭に記録される。地表/地中スペクトル比は,概ね奇数倍の周波数列にシャープなピークを有する。また,水平動/上下動スペクトル比には盆地の基盤構造に由来する山谷が顕著に現れる。これらのデータを基に,‐深さ約600mの基盤岩までの地盤のS波速度とQ値のモデル化を行った。S波のQ値は,周波数の1乗に,またs波速度の2‐3乗に依存していた。構造モデルから推定される地盤の固有周期は基本モードで約3秒,増幅率は広い周波数範囲で約4倍であった。To elucidate subsurface structure and ground vibration characteristics at Heijo, Nara basin, where 'Daigokuden', government office in the Nara era is planned to be restored to its original state, seismic observation has been carried out at GL Om, -20m, -42m and - lOOm in a borehole. The depth to bedrock is known to be about 600m from nearby deep boreholes. It is notable that, almost all the seismograms showremarkable SP phases generated at the soil-bedrock boundary and down-going S-waves reflected at groundsurface. We made spectral analyses of S wave parts including preceding SP phases; surface-to-subsurface spectral ratios (Ho/H-d) and horizontal-to-vertical spectral ratio (H/V). Ho/l-l-d shows sharp peaks at oddmultiple frequencies. Remarkable peaks and troughs of fundamental mode in H/V are observed, even though incident angle of SV phases at bedrock exceed the critical angle (arcsin (Vs/Vp); V in bedrock). We estimated S wave velocity and Q structure using Haskell method. As a result, it was found that, Qs depends on 1stpower of frequency and 2nd to 3rd power of Vs, fundamental natural-period of ground is 3s, andsoil-amplification is about 4 for 1-20Hz
THEORY OF CONDITIONAL RANDOM FIELDS AND ITS ENGINEERING APPLICATION
No full textThis paper outlines the theory of conditional random fields and its application.Probabilistic relations of conditional random fields are analytically developed; that is conditional means, first passage solution of conditional random fields, and method of digital simulation.In particular, an approximate method of digital simulation is presented that ensures stability of computational calculations.Conditional fields of earthquake ground motions are discussed for power spectral density and coherence functions determined statistically or derived from analysis of elastic waves propagating through a random medium.Time variations of wind speed are digitally simulated, as another engineering application of a conditional random field, using power spectral density functions fitted for observation in a wind tunnel.This paper outlines the theory of conditional random fields and its application.Probabilistic relations of conditional random fields are analytically developed; that is conditional means, first passage solution of conditional random fields, and method of digital simulation.In particular, an approximate method of digital simulation is presented that ensures stability of computational calculations.Conditional fields of earthquake ground motions are discussed for power spectral density and coherence functions determined statistically or derived from analysis of elastic waves propagating through a random medium.Time variations of wind speed are digitally simulated, as another engineering application of a conditional random field, using power spectral density functions fitted for observation in a wind tunnel
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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