Yoshiki Matsuda

Ih blockers have a potential of antiepileptic effects.

Summary:  Purpose: The h current (Ih) is an inwardly mixed cationic conductance activated by membrane hyperpolarization and distributed predominantly in the apical dendrites of hippocampal pyramidal neurons. To verify a hypothesis that an anomalous hyperpolarization generates an abnormal excitation by way of Ih channels, we examined the effects of Ih blockers (CsCl and ZD7288) on electrically induced paroxysmal discharges (PADs).

Behavioral and cortical EEG evaluations confirm the roles of both CCKA and CCKB receptors in mouse CCK-induced anxiety.

This study investigated the roles of cholecystokinin (CCK)(A) and CCK(B) receptors on CCK-4-induced anxiety-like behaviors in mice through behavioral and neural evaluations. Anxiety-like behaviors in mice were induced by an intracerebroventricular (i.c.v.) administration of CCK-4, which can bind to both CCK(A) and CCK(B) receptors. The effects of CCK(A) and CCK(B) receptor antagonists (devazepide and CI-988, respectively) were examined using mouse anxiety tests (elevated-plus maze and light-dark box) and also by examining neuronal activities through EEG monitoring and c-Fos immunohistochemistry in the cortex and amygdala. CCK-4 (3 μg/kg of body weight i.c.v.) significantly induced mouse anxiety-like behaviors in the anxiety tests and also affected their EEG patterns with respect to pre-drug tracing, resulting in increase in spectral power in relative power distribution in the delta and theta bands (0.5-5 Hz frequency bands) and also in increase in c-Fos immunopositive neuron counts. These CCK-4 effects were completely suppressed by 1.0mg/kg CCK(B) receptor antagonist, CI-988, while the same amount of CCK(A) receptor antagonist, devazepide was partly able to suppress the same effects. These findings indicated that not only CCK(B) receptors but also CCK(A) receptors in the brain play important roles in regulating anxiety-like behaviors in mice. The present study also proposed a possibility that cortical EEG is useful for assessing anxiety.

Simultaneous Kindling of the Bilateral Hippocampi: An Advanced Model for Epilepsy Research

Summary: Purpose: To examine whether simultaneous kindling of bilateral hippocampi [bilateral kindling (BK)] could accelerate the achievement of seizures by the breakdown of kindling antagonism or decelerate the achievement of seizures by its enhancement.

Epileptogenesis Induced by Alternate-site Kindling in Bilateral Hippocampi

Summary:  Purpose: Alternate‐site kindling (AK), which has been known to induce so‐called kindling antagonism, was performed in the bilateral hippocampi to reveal neural mechanisms underlying hippocampal kindling.

The extracellular current blocking effect of cesium chloride on the theta wave in the rabbit hippocampal CA1 region

We studied the extracellular effects of cesium chloride (CsCl), a blocker of the hyperpolarization-activated cationic current (I(h)), on the hippocampal theta wave in pentobarbital-anesthetized rabbits. We recorded spontaneous field potentials at the hippocampal CA1 region before and at three time periods after CsCl or saline injections. We found that CsCl injected into the apical dendritic layer attenuated the theta wave amplitude. CsCl affected neither the frequency nor the phase reversal of the theta wave between the apical and basal dendritic layers. Our findings indicate that I(h) in pyramidal neurons contributes to current generation of the limbic theta wave in vivo.

Effects of 808 nm low-power laser irradiation on the muscle contraction of frog gastrocnemius

The efficacy of low‐power laser irradiation (LLI) on muscle fibers remains unclear; therefore, we examined the effect of LLI (808 nm: 60 or 100 mW) on muscle contraction and conducted waveform analyses of the twitch curve, including alterations in the peak amplitudes of tension (AMP), latency (LAT), contraction period (CP), and relaxation period (RP).

Fewer GABAergic interneurons, heightened anxiety and decreased high-frequency electroencephalogram components in Bronx waltzer mice, a model of hereditary deafness.

The homozygous Bronx waltzer mutation (bv/bv) results in the degeneration of most but not all of the primary auditory receptors, the inner hair cells and their afferent neurons, and leads to perceptive deafness. However, the influence of the mutation on the central nervous system (CNS) remains largely unclear. In this study, we have conducted behavioral, morphological and electrophysiological investigations to clarify the CNS dysfunction in bv/bv mice. These mutant mice exhibited heightened levels of anxiety with normal levels of motor activity. Immunohistochemical analysis revealed a significant reduction in parvalbumin-containing GABAergic interneurons in the anterior cingulate, somatosensory and auditory cortices of bv/bv mice. The current results suggest that interneuron development may be disrupted in the bv/bv cerebrum. Moreover, the high-frequency electroencephalogram components of the cortical activity, including the frequency range containing high gamma, were markedly decreased in bv/bv mice compared with controls, probably indicating a disturbance in cortical inhibitory function. Together, these results suggest that the cortical development of interneurons and their electrophysiological profiles are altered in bv/bv mice. We propose that these novel phenotypes identified in bv/bv mice provide new perspectives on the basic neuronal mechanisms of developmental disorders.

Effects of Hyperpolarization-Activated Channel Blocker ZD7288 on Polar Excitations of Frog Sciatic Nerve

Previous studies have demonstrated that Ar(+) laser irradiation shows a more selective blocking effect on the generation of anode-break-excitation (AE) than on cathode-make-excitation (CE), and that the effects of laser irradiation closely resemble those following the application of hyperpolarization-activated current (Ih) blocker, ZD7288. We therefore examined the effects of ZD7288 and tetrodotoxin (TTX) on polar excitations to reveal whether such a selective effect of ZD7288 on AE is specific in frog sciatic nerve. Supramaximal stimuli (10-ms pulse) were applied while for 30 min each channel blocker was applied to the stimulating sites. Analyses of chronological changes in polar excitations were performed using CEs induced by positive stimuli and AEs induced by negative stimuli, because both were generated on the same stimulating grid against the recording grids. TTX application (1 mM) decreased all types of polar excitations at 30 min after initiation of the application. When ZD7288 (1 mM) was applied, the amplitude of AE displayed a significant decrease after 30 min. When TTX or ZD7288 was applied to the middle portion between the stimulating and recording electrode grids, TTX showed the conduction block, but the latter yielded almost no effect. Western blotting analyses demonstrated expressions of the second and the third subunits of hyperpolarization-activated and cyclic-nucleotide-gated nonselective cation channels in frog sciatic nerve. Ih channels thus exist in the frog sciatic nerve, and its specific blocker, ZD7288, has the potential to selectively block the generation of AE.

Developmental changes of anxiety-related behaviors in Bronx waltzer mice

Riluzole, a drug currently used to slow the progression of amyotrophic lateral sclerosis (ALS), directly affects the glutamatergic system. Growing evidence indicated that the glutamatergic neurotransmitter system is central to the neurobiology and treatment of mood and anxiety disorders. It has been reported that many behavioral changes, such as hyperemotional responses and anxiety-like behaviors, observed in olfactory bulbectomy (OBX) of rats were improved by subchronic treatment of antidepressants. Recently, we showed that riluzole attenuated hyperemotional responses in a rat OBX model of depression. The present study examined the effects of riluzole on an anxiety-like behaviors in OBX rats. The olfactory bulbs in rats were removed by suction. Riluzole was administered p.o. once daily. The anxietylike behavior of rats was measured by elevated plus maze test. The OBX rats chronically treated with vehicle for 8 days at 14 days following surgery showed decreases in the time spent on the open arm of a plus-maze. Subchronic riluzole treatment (1–3 mg/kg) in OBX rats significantly increased the time spent on the open arm of the plus-maze, whereas subchronic riluzole treatment (1–10 mg/kg) in OBX rats significantly decreased the time spent on the closed arm of the plus-maze. Subchronic riluzole treatment (10 mg/kg) in sham operated rats had no significant effects on the time spent on both open and closed arms of the plus-maze. On the other hand, total number of entries to closed and open arms were significantly increased in OBX rats by subchronic treatment with riluzole (1–10 mg/kg), whereas no differences was found between vehicle and riluzole subchronic treatment in sham rats. Based on these results, we suggest that riluzole reduces the anxietylike behaviors similarly to hyperemotional responses in OBX rats, an animal model of depression. In conclusion, our results suggest that riluzole could improve symptoms in the mood and anxiety disorders. Research fund: Japan Fundation for Neuroscience and Mental Health.

Anomalous properties of cortical inhibitory neural mechanism in behavioral dysfunction of the Bronx waltzer mouse

The aim of our study is to establish an animal model of olfactory hypersensitivity to volatile organic compounds (VOCs) and to apply the model for pathological understanding of VOC-related human disorders such as sick house syndrome. We developed a system for evaluating olfactory detection of VOCs in mice, which is composed of a standard operant chamber, an odor-sniffing glassy port, solenoid valves, diaphragm pumps, two polyethylene gas bags, and a personal computer. Male mice were trained for an operant learning task of pressing the levers coresponding to sniffed gas, and then they performed a session of tasks to discriminate between VOC gas with various concentrations and pure nitrogen gas. We found that the detection thresholds of the two VOC gas (toluene and dichloromethane (DCM)) in mice were below the limit of finding with our system but that the accuracy for detecting DCM with fixed concentration (100 ppb) may be a useful index in mice for monitoring olfactory sensitivity within or after the period with repeated exposure to VOC gas.