PubMed Health⌕ Search

Biomedical subjects

Minoru Tsukada

Publications and source records attributed to Minoru Tsukada.

10 recordsLinked to original sources

Reproducing bursting interspike interval statistics of the gustatory cortex.

Cortical neurons in vivo generate highly irregular spike sequences. Recently, it was experimentally found that the local variation of interspike intervals, LV, is nearly constant for every spike sequence for the same neurons. On the contrary, the coefficient of variation, CV, varies over different spike sequences. Here, we first show that these characteristic features are also applicable in bursting spike sequences that are obtained from the rat gustatory cortex. Next, we show that the conventional leaky integrate-and-fire model does not fully account for reproducing these statistical features in data of real bursting spike sequences. We resolve this difficulty by proposing an alternative neuron model which is a reduction of the bursting neuron model involving the persistent sodium current. Our study implies that (1) the characteristic features of CV and LV are the results of the endogenous bursting and (2) the bursting behavior in the gustatory cortex is caused mainly by the persistent sodium current.

Animals↗

Role of the thrombin/protease-activated receptor 1 pathway in intestinal ischemia-reperfusion injury in rats.

CXC chemokines, including human interleukin-8 and rat cytokine-induced neutrophil chemoattractant-1, play a crucial role in the pathogenesis of intestinal inflammation induced by ischemia-reperfusion (I-R). Thrombin and its specific receptor, protease-activated receptor 1 (PAR1), act as important players in inflammation. However, the association between thrombin activation and chemokine production during I-R has not been well studied. We investigated whether thrombin and PAR1 might be involved in the pathophysiology of intestinal I-R, using an in vivo model. Intestinal damage was induced by clamping the superior mesenteric artery for 30 min followed by reperfusion in male Wistar rats. Thrombin-antithrombin complex was measured as an indicator of thrombin activation. PAR1 expression in the intestine was evaluated by real-time PCR. The severity of the intestinal mucosal injury was evaluated on the distal segment of the ileum by several biochemical markers and histological findings. Reperfusion significantly increased the serum levels of thrombin-antithrombin complex and enhanced PAR1 expression in the intestinal mucosa. The levels of both intraluminal hemoglobin and protein were significantly increased in the I-R group. The mucosal myeloperoxidase activity and expressions and/or productions of cytokine-induced neutrophil chemoattractant-1 and TNF-alpha were significantly increased after I-R. These increases were inhibited by the treatment of rat with antithrombin intravenously before I-R at a dose of 30 U/kg. These results suggest that the thrombin/PAR1 pathway plays an important role in the production of these cytokines during I-R and that antithrombin exerts potent anti-inflammatory effects on this injury via inhibition of proinflammatory cytokines.

Animals↗

Recombinant human antithrombin expressed in Chinese hamster ovary cells shows in vivo efficacy on rat DIC model similarly to plasma-derived antithrombin regardless of different N-glycosylation.

Plasma-derived human antithrombin (pAT) is used for the treatments of disseminated intravascular coagulation (DIC) and hereditary antithrombin deficiencies. We expressed recombinant human antithrombin (rAT) in Chinese hamster ovary (CHO) cells. The purified rAT is composed of 55% alpha-isoform and 45% beta-isoform. The structure of the N-linked oligosaccharides of rAT is the same biantennary complex type as previously found in pAT with less sialylated on the non-reducing ends. Most of the oligosaccharides of rAT are fucosylated at the reducing ends of N-acetylglucosamine, while those of pAT are not fucosylated. Despite of the difference in sialylation and fucosylation of the oligosaccharide units, rAT and pAT showed indistinguishable heparin cofactor and progressive activities, and they bound to thrombin in a one-to-one stoichiometric manner. In lipopolysaccharide (LPS)-induced and thromboplastin-induced DIC rat models, rAT reduced fibrinogen and platelet consumption to a similar extent with pAT. In LPS-induced DIC model, both ATs similarly restrained the increase of alanine aminotransferase and aspartate aminotransferase activities. Finally, pharmacokinetic analysis showed that both ATs had similar half-lives in the circulation of normal rats. Together, the present study demonstrated that rAT prepared in CHO cells has potential for a substitute of pAT in therapeutic use.

Alanine Transaminase↗

A model of the hippocampal-cortical memory system.

Based on physiological evidence, we propose a theoretical model of the hippocampal-cortical memory system. The model consists of the following components: the sensory system, the hippocampus (short-term memory), and the association cortex (long-term memory). A series of key codes (local information) is supplied from the sensory system, while context (global information) is inputted from the hippocampus. The two inputs interact dynamically in the association cortex. The interactive neurons work as a detector of coincidence. The cortical network learns the memory information through the coincidence window and, finally, stores it in the form of attractors. This local-global information works as an addressor to designate the stored location of the memory in the association cortex and accelerates the process of storing and retrieving memory information.

Action Potentials↗

Change detection and difference detection of tone duration discrimination.

An event-related potential called mismatch negativity is known to exhibit physiological evidence of sensory memory. Mismatch negativity is believed to represent complicated neuronal mechanisms in a variety of animals and in humans. We employed the auditory oddball paradigm varying sound durations and observed two types of duration mismatch negativity in anesthetized guinea pigs. One was a duration mismatch negativity whose increase in peak amplitude occurred immediately after onset of the stimulus difference in a decrement oddball paradigm. The other exhibited a peak amplitude increase closer to the offset of the longer stimulus in an increment oddball paradigm. These results demonstrated a mechanism to percept the difference of duration change and revealed the importance of the end of a stimulus for this perception.

Acoustic Stimulation↗

Spatiotemporal visualization of long-term potentiation and depression in the hippocampal CA1 area.

Long-term potentiation (LTP) in the CA1 area of the hippocampus depends critically on the statistical characteristics of its stimulus. The ability of optical imaging to record spatial distribution has made it possible to examine systematically the effect of higher-order statistical characteristics, such as the correlation between successive pairs of inter-stimulus intervals (ISIs) on the induction of LTP. Therefore, the function of frequency (first-order) and temporal pattern (second-order) was examined using this imaging technique. To investigate the dependence of LTP on frequency, periodic stimuli with the same number of pulses were applied at different frequencies (1-10 Hz, n=200) to Schaffer commissural-collateral fibers. While stimulus frequencies from 2-10 Hz induced LTP of varying magnitudes and low-frequency stimuli (1 Hz) induced long-term depression (LTD), spatial distribution remained consistent. These results suggest that induction frequency has a greater effect on the magnitude of LTP than on its spatial distribution. By employing nonperiodic stimuli at the same mean frequency (2 Hz), the effect of varying the temporal structure of a stimulus was also investigated. As the correlation of successive ISIs was increased from negative to positive, not only did the magnitude of LTP increase, there was also a statistically significant change in the spatial distribution of LTP. Interestingly, when a strong negatively correlated stimulus was applied, both LTP and LTD were simultaneously observed in the CA1 area. It was also found that the magnitude of LTP 200-300 mum distal to the cellular layer was larger than that of the LTP induced proximal (<100 microm) to that layer. These results support the hypothesis that the spatial distribution of LTP throughout the hippocampus relies principally on the temporal patterning of input stimulation. This insight into the structure of the CA1 neural network may reveal the importance of stimulus timing events in the spatial encoding of memories.

Action Potentials↗

Spatial analysis of spike-timing-dependent LTP and LTD in the CA1 area of hippocampal slices using optical imaging.

Spike-timing-dependent long-term potentiation (LTP) and long-term depression (LTD) were investigated in the CA1 area of hippocampal slices using optical imaging. A pair of electrical pulses were used to stimulate the Schaffer-commissural collateral and the stratum oriens with various sets of relative timing (tau) between the two stimuli. These sets of paired pulses gave rise to LTP/LTD, whose induction was closely related to tau, and their profiles were classified into two types depending on their layer specific location along the dendrite. One was characterized by a symmetric time window observed in the proximal region of the stratum radiatum (SR) and the other by an asymmetric time window in the distal region of the SR. Bath application of bicuculline (gamma-aminobutyric acid [GABA] receptor antagonist) to hippocampal slices revealed that GABAergic interneuron projections were responsible for the symmetry of a time window.

Action Potentials↗

Plasma levels of heparin cofactor II (HCII) and thrombin-HCII complex in patients with disseminated intravascular coagulation.

Plasma levels of heparin cofactor II (HCII), thrombin-HCII complex (THC), antithrombin (AT), and thrombin-AT complex (TAT) were evaluated in patients with disseminated intravascular coagulation (DIC) associated with several underlying diseases. Plasma levels of AT were significantly reduced in almost all underlying diseases associated with DIC, but the plasma levels of HCII and HCII/AT ratio were significantly reduced only in patients with infections. While the plasma level of TAT was significantly increased in patients with all underlying diseases associated with DIC, the increase of THC was not significant. Plasma levels of AT were significantly reduced in DIC and pre-DIC associated with almost all underlying diseases, but those of HCII were significantly reduced only in DIC and pre-DIC patients with inflammatory diseases. The plasma levels of TAT were significantly increased in DIC, pre-DIC, and non-DIC patients with all underlying diseases, and those of THC were significantly increased in DIC and pre-DIC patients with inflammatory diseases. The plasma levels of THC were not significantly increased in non-DIC patients of any disease group. The decrease of AT may be caused by thrombin generation or inflammatory reaction that occurs in DIC associated with underlying diseases, while the decrease of HCII might be caused by both thrombin generation and inflammatory reaction. Finally, AT inhibits thrombin more strongly than HCII in several underlying diseases associated with DIC except for inflammatory diseases. In inflammatory diseases, HCII might play an important role in preventing the onset of DIC.

Antithrombin III↗

Hippocampal LTP Depends on Spatial and Temporal Correlation of Inputs.

We studied the LTP inducing factors using temporally and spatially modulated stimuli given to the hippocampal neural network. It was found that when the spatial factors were maintained to be constant the positive correlation in the successive inter-stimulus intervals contributes to produce larger LTP. On the other hand, if the temporal factors are kept constant, the spatial coincidence contributes to produce larger LTP. We propose a learning rule by which these experimental results can be consistently interpreted. Copyright 1996 Elsevier Science Ltd.

Journal Article↗

Dynamical Cell Assembly Hypothesis - Theoretical Possibility of Spatio-temporal Coding in the Cortex.

This paper is an attempt to understand how knowledge and events are represented and processed in the brain. An important point is the question of what carries information in the brain - the mean firing rate or the timing of spikes? The idea we want to pursue is that, contrary to the traditional view, the brain might use higher order statistics, which means in essence that timing of spikes plays a critical role in encoding, representing, and processing knowledge and events in the brain.A recently revealed salient nature of cortical pyramidal cells, i.e., the high variability of inter-spike intervals suggests that a cortical neuron may function effectively as a coincidence detector. At the same time, non-classical experimental phenomena of task-related, short time-scaled dynamical modulations of temporal correlations between neurons suggest a non-classical view on the dynamics working in the brain. In response to contexts or external events, a group of neurons, a dynamical cell assembly, spontaneously organizes, linked temporarily by coincident timing of incident spikes, showing correlated firing with each other. This is an emergent property of neuronal populations in the cortex.We make a theoretical exploration on issues as (1) the description of such emergent dynamics of dynamical cell assemblies based on the working hypothesis that a cortica neuron functions effectively as a coincidence detector, and (2) the principle of spatio-temporal coding based on the hypothetical emergent dynamics. Note that the conventional rate coding hypothesis does not give satisfactory answers to fundamental questions on the representation and processing of knowledge or events in the brain, e.g., the questions of cross-modular integration of information or the binding problem, and representation of hierarchical knowledge etc.The first goal is to give a non-encyclopedic review on (1) the temporal structure of spike sequences, focusing on the question of the basic code in the brain; (2) the paradigms on representation of knowledge and events proposed from a theoretical or experimental basis. The classical paradigms of Hebb and Barlow with their experimental and theoretical critiques, and more recently proposed experiment-based paradigms are reviewed. Also a review is given on (3) the experimentally observed spatio-temporal structure of spike dynamics.The second goal is to give a description of the dynamical cell assembly - the central concept in this paper. Aside from the question of physiological basis, we make a theoretical study, under a working hypothesis that a cortical neuron functions effectively as a coincidence detector, on the emergent dynamics of cell assemblies, and also examine how the observed experimental data could be explained within this theoretical setting.We also try to give the principle of spatio-temporal coding based on the dynamical cell assembly framework. A key concept is the internal mechanism of "dialogue" among neuronal pools in the brain. This provides a dynamical foundation of bi-directional interactions for the linkage of distant modules to create integrated information. We present a simple model in order to illustrate the working principle of coincidence detector systems. Relations with other temporal coding paradigms are also discussed. Copyright 1996 Elsevier Science Ltd.

Journal Article↗