Tatsuo Kitajima

An ESR-CT imaging of the head of a living rat receiving an administration of a nitroxide radical

Three-dimensional ESR imaging of a living rat has been performed by an L-band ESR system, which is composed of an L-band ESR spectrometer, a field gradient coil, and a data processor. The imaging was carried out by Lauterburs method. A nitroxide, 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (Carbamoyl-PROXYL), was used as an imaging agent in saline solution at a concentration of 0.2 M and administered intraperitoneally to obtain a constant concentration in the head for about an hour. It took about 40 min to obtain one set of ESR-CT images. The cross-sectional images were made, both as coronal and horizontal images. In the images of the rat head the nitroxide-rich region was clearly distinguished from the deficient region. The nitroxide-deficient areas corresponded well to the brain of the rat.

Construction of fibroblast–collagen gels with orientated fibrils induced by static or dynamic stress: toward the fabrication of small tendon grafts

As a step toward the fabrication of small tendon grafts, fibroblast–collagen gels were constructed with orientated fibrils induced by static or dynamic loading. Three groups of gel samples, each consisting of 1.0 × 106 fibroblasts and 2 mg type I collagen, were fabricated: freely contracted gels formed the control group; contraction-directed gels made up the static group (the gel contraction was directed perpendicular to an axis made by two anchors buried in the gels so that the constraint stress exerted by the two anchors was imposed on the gel); and for the dynamic group, a specific loading pattern (free contraction followed by cyclic stretching using a tensile bioreactor) was employed. Mechanical properties were evaluated by means of the uniaxial tension test. The gels of the static group had an ultimate stress of 350 ± 43.6 kPa and a material modulus of 548.8 ± 61.6 kPa, which were almost 5.2 times and 15.6 times, respectively, greater than those of the controls. The dynamic gels had an ultimate stress of 256.8 ± 80.7 kPa and a material modulus of 118.6 ± 23.5 kPa. These results show that the ultimate stress and material modulus of the static samples are much greater than those of the dynamic samples, which is the opposite of our expectations. Therefore, studies under other dynamic loading patterns and long-term culture are needed to clarify whether dynamic loading is superior to static loading.

A generalized Hebbian rule for activity-dependent synaptic modification

In this paper our previous model of activity-dependent synaptic modification is extended and applied to a model neuron with active dendrites and is used in computer simulations to examine in detail the dependence of synaptic modifications on the interval between the onset of excitatory postsynaptic potentials (EPSPs) and postsynaptic action potentials (APs). The EPSP amplitude is increased when the action potentials occur within 20 ms after EPSPs and is reduced when the action potentials occur within 20 ms before EPSPs. Furthermore, the absolute value of changes in the EPSP amplitude tends to increase as the interval between APs and EPSPs decreases. A learning rule for synaptic modifications described in this paper may, hence, further generalize the Hebbian rule which requires conjunctive presynaptic and postsynaptic activity for synaptic modification to occur. Functional roles for such a generalized Hebbian rule are also considered.

A model for synaptic development regulated by NMDA receptor subunit expression

Activation of NMDA receptors (NMDARs) is highly involved in the potentiation and depression of synaptic transmission. NMDARs comprise NR1 and NR2B subunits in the neonatal forebrain, while the expression of NR2A subunit is increased over time, leading to shortening of NMDAR-mediated synaptic currents. It has been suggested that the developmental switch in the NMDAR subunit composition regulates synaptic plasticity, but its physiological role remains unclear. In this study, we examine the effects of the NMDAR subunit switch on the spike-timing-dependent plasticity and the synaptic weight dynamics and demonstrate that the subunit switch contributes to inducing two consecutive processes—the potentiation of weak synapses and the induction of the competition between them—at an adequately rapid rate. Regulation of NMDAR subunit expression can be considered as a mechanism that promotes rapid and stable growth of immature synapses.

A model of the mechanisms of long-term potentiation in the hippocampus

Long-Term Potentiation (LTP) in the hippocampus has been considered to be a phenomenon closely related to learning and memory in the brain. In this paper, an integrated model of LTP is constructed based on hypotheses about both the mechanism of LTP induction and that of LTP maintenance, that is, the NMDA-receptor channel, protein phosphorylation and protein turnover. The validity of the model is discussed based on the results of computer simulations.

Possible role of cooperative action of NMDA receptor and GABA function in developmental plasticity

The maturation of cortical circuits is strongly influenced by sensory experience during a restricted critical period. The developmental alteration in the subunit composition of NMDA receptors (NMDARs) has been suggested to be involved in regulating the timing of such plasticity. However, this hypothesis does not explain the evidence that enhancing GABA inhibition triggers a critical period in the visual cortex. Here, to investigate how the NMDAR and GABA functions influence synaptic organization, we examine an spike-timing-dependent plasticity (STDP) model that incorporates the dynamic modulation of LTP, associated with the activity- and subunit-dependent desensitization of NMDARs, as well as the background inhibition by GABA. We show that the competitive interaction between correlated input groups, required for experience-dependent synaptic modifications, may emerge when both the NMDAR subunit expression and GABA inhibition reach a sufficiently mature state. This may suggest that the cooperative action of these two developmental mechanisms can contribute to embedding the spatiotemporal structure of input spikes in synaptic patterns and providing the trigger for experience-dependent cortical plasticity.

An integrated model for activity-dependent synaptic modifications

Abstract An integrated model is proposed for activity-dependent synaptic modifications. These include two forms of homosynaptic modification, two forms of associative modification and one form of heterosynaptic modification. The model is constructed by referring to the physiological and biochemical data that likely underlie the induction and expression of long-term potentiation and long-term depression and by making certain assumptions. Computer simulations are performed, and the simulation results prove to have good agreement with relevant experimental results. Thus, the model may produce realistically different forms of synaptic modification.

A model of the mechanism of cooperativity and associativity of long-term potentiation in the Hippocampus: a fundamental mechanism of associative memory and learning

Long-Term Potentiation (LTP) has three properties: (1) input specificity, (2) cooperativity and (3) associativity. In a previous paper, we proposed an integrated model of the mechanisms of the induction and maintenance of LTP with input specificity. In this paper, a model of the mechanism of cooperative and associative LTP is described. According to computer simulations of the model, its mechanism is based on the spread of synaptic potentials.

Mathematical Modeling of Subthreshold Resonant Properties in Pyloric Dilator Neurons

Various types of neurons exhibit subthreshold resonance oscillation (preferred frequency response) to fluctuating sinusoidal input currents. This phenomenon is well known to influence the synaptic plasticity and frequency of neural network oscillation. This study evaluates the resonant properties of pacemaker pyloric dilator (PD) neurons in the central pattern generator network through mathematical modeling. From the pharmacological point of view, calcium currents cannot be blocked in PD neurons without removing the calcium-dependent potassium current. Thus, the effects of calcium (I Ca) and calcium-dependent potassium (I KCa) currents on resonant properties remain unclear. By taking advantage of Hodgkin-Huxley-type model of neuron and its equivalent RLC circuit, we examine the effects of changing resting membrane potential and those ionic currents on the resonance. Results show that changing the resting membrane potential influences the amplitude and frequency of resonance so that the strength of resonance (Q-value) increases by both depolarization and hyperpolarization of the resting membrane potential. Moreover, hyperpolarization-activated inward current (I h) and I Ca (in association with I KCa) are dominant factors on resonant properties at hyperpolarized and depolarized potentials, respectively. Through mathematical analysis, results indicate that I h and I KCa affect the resonant properties of PD neurons. However, I Ca only has an amplifying effect on the resonance amplitude of these neurons.

Analysis of the contraction of fibroblast-collagen gels and the traction force of individual cells by a novel elementary structural model

Based on the experimental data of the contraction ratio of fibroblast-collagen gels with different initial collagen concentrations and cell numbers, we analyzed the traction force exerted by individual cells through a novel elementary structural model. We postulate that the mechanical mechanism of the gel contraction is mainly because that populated cells apply traction force to some of the surrounding collagen fibrils with such proper length potential to be pulled straight so as to be able to sustain the traction force; this traction induce the cells moving closely to each other and consequently compact the fibrillar network; the bending force of the fibrils in turn resists the movement. By employing fiber packing theory for random fibrillar networks and network alteration theory, the bending force of collagen fibrils was deduced. The traction force exerted by individual fibroblasts in the gels was balanced by the bending force and the resistance from interstitial fluid since inertial force can be neglected. The maximum traction force per cell under free floating condition is in the range of 0.27-9.02 nN depending on the initial collagen concentration and populated cell number. The most important outcome of this study is that the traction force of individual cells dynamically varies under different gel conditions, whereas the adhesion force between cell and individual fibrils is relatively converging and stable.