Haploinsufficiency of the voltage-gated sodium channel Na V 1.1 causes Dravet syndrome, an intractable developmental epilepsy syndrome with seizure onset in the first year of life. Specific heterozygous deletion of Na V 1.1 in forebrain GABAergic-inhibitory neurons is sufficient to cause all the manifestations of Dravet syndrome in mice, but the physiological roles of specific subtypes of GABAergic interneurons in the cerebral cortex in this disease are unknown. Voltage-clamp studies of dissociated interneurons from cerebral cortex did not detect a significant effect of the Dravet syndrome mutation on sodium currents in cell bodies. However, current-clamp recordings of intact interneurons in layer V of neocortical slices from mice with haploinsufficiency in the gene encoding the Na V 1.1 sodium channel, Scn1a, revealed substantial reduction of excitability in fast-spiking, parvalbumin-expressing interneurons and somatostatin-expressing interneurons. The threshold and rheobase for action potential generation were increased, the frequency of action potentials within trains was decreased, and action-potential firing within trains failed more frequently. Furthermore, the deficit in excitability of somatostatin-expressing interneurons caused significant reduction in frequency-dependent disynaptic inhibition between neighboring layer V pyramidal neurons mediated by somatostatin-expressing Martinotti cells, which would lead to substantial disinhibition of the output of cortical circuits. In contrast to these deficits in interneurons, pyramidal cells showed no differences in excitability. These results reveal that the two major subtypes of interneurons in layer V of the neocortex, parvalbumin-expressing and somatostatin-expressing, both have impaired excitability, resulting in disinhibition of the cortical network. These major functional deficits are likely to contribute synergistically to the pathophysiology of Dravet syndrome. D ravet syndrome (DS), also referred to as "severe myoclonic epilepsy in infancy," is a rare genetic epileptic encephalopathy characterized by frequent intractable seizures, severe cognitive deficits, and premature death (1-3). DS is caused by loss-of-function mutations in SCN1A, the gene encoding type I voltage-gated sodium channel Na V 1.1, which usually arise de novo in the affected individuals (4-7). Like DS patients, mice with heterozygous lossof-function mutations in Scn1a exhibit ataxia, sleep disorder, cognitive deficit, autistic-like behavior, and premature death (8)(9)(10)(11)(12)(13)(14). Like DS patients, DS mice first become susceptible to seizures caused by elevation of body temperature and subsequently experience spontaneous myoclonic and generalized tonic-clonic seizures (11). Global deletion of Na V 1.1 impairs Na + currents and action potential (AP) firing in GABAergic-inhibitory interneurons (8-10), and specific deletion of Na V 1.1 in forebrain interneurons is sufficient to cause DS in mice (13,15). These data suggest that the loss of interneuron excitability and resulting di...

Main objective of the LATE (Low Aspect ratio Torus Experiment) device is to demonstrate formation of ST plasmas by electron cyclotron heating (ECH) alone without center solenoid. By injecting a 2.45 GHz microwave pulse up to 30 kW for 4 seconds, a plasma current of 1.2 kA is spontaneously initiated under a weak steady vertical field of B v = 12 Gauss, and then ramped up with slow ramp-up of B v for the equilibrium of the plasma loop and finally reaches 6.3 kA at B v = 70 Gauss. This currents amount 10 percents of the coil currents of 60 kAT for the toroidal field. Magnetic measurements show that an ST equilibrium, having the last closed flux surface with an aspect ratio of R 0 /a 20.4 cm/14.5 cm 1.4, an elongation of κ = 1.5 and q edge = 37, has been produced and maintained for 0.5 s at the final stage of discharge. The plasma center locates near the second harmonic EC resonance layer and the line averaged electron density significantly exceeds the plasma cutoff density, suggesting that the second harmonic EC heating by the mode-converted electron Bernstein waves (EBW) support the plasma. Spontaneous formation of ST equilibria under steady B v fields, where plasma current increases rapidly in the time scale of a few milliseconds, is also effective and a plasma current of 6.8 kA is spontaneously generated and maintained at B v = 85 Gauss by a 5 GHz microwave pulse (130 kW, 60 ms).

We developed a comprehensive cell model that simulates the sequential cellular events from membrane excitation to contraction in the human ventricle. By combining this ventricular cell model with a lumped circulation model, we examined how blood pressure dynamics in the ventricle and aorta are related to the cellular processes. To convert cell contraction into ventricular pressure using Laplace's law, we introduced a simple geometric model of a ventricle: one shaped like a thin-walled hemisphere. The force of contraction of a single cell induces tension in the hemispheric ventricular wall, which generates the ventricular and aortic pressures in the lumped circulation model. The time courses of the hemodynamic properties, as well as the volume-pressure trajectory of the left ventricle, were well reproduced. Our multi-scale cardiovascular model, which covers from cardiac cells to the circulatory system, simulates the typical characteristics of heart mechanics, such as the pressure-volume relationship, stroke volume and the effect of the increased maximum free calcium concentration on cardiovascular hemodynamics. To test the cell-circulation coupling characteristics of the model, we simulated the effects of a decrease in L-type calcium channel conductance (cell level) on left ventricular pressure (system level). The variation due to different pacing frequencies for myocyte excitation was also investigated to assess the effects of heart rate on cardiac cells and the circulatory system.

ABSTRACT. The age-related changes in two types of theta rhythms recorded from the hippocampus in young (4 months-old), mature (12-13 months-old) and aged (22-25 months-old) rats were investigated. The type 1 theta rhythm was measured from hippocampal EEG recorded from walking rats and the type 2 theta was measured from the EEG induced by reticular pontin oralis nucleus (PON) stimulation in urethane anesthetized rats. The peak frequency and the peak power were detected from power spectra calculated on each theta sample by fast Fourier transformation (FFT). No age-related alteration was observed on the peak frequency of type 1 theta rhythm. However, on type 2 theta rhythm, the peak frequency was decreased in the aged rats compared with the young and the mature rats. The type 2 theta rhythm is cholinergic, and therefore this result suggests that age-related deterioration can be clearly observed in the cholinergic system including the hippocampus in rats.-KEY WORDS: aging, hippocampus, rat, theta rhythm.J. Vet. Med. Sci. 61 (5): [543][544][545][546][547][548] 1999 theta rhythms and aging remains unclear.In this study, we attempted to clarify the age-related changes in the two types of hippocampal theta rhythms associated with different pharmacological systems. MATERIALS AND METHODSMale Wistar rats supplied by SLC Co., Ltd. were used in this study. For the measurement of the type 1 theta, three aged rats (22-25 months-old), four mature rats (12-13 months-old) and four young rats (3-4 months-old) were used. For the type 2 theta, four aged rats, four mature rats and three young rats were used. Aged and mature rats were purchased as retired rats (6-7 months-old) and housed in our animal facility for 6 months and 18 months respectively. The animal facility was maintained on a 12 hr light/dark cycle, at 21 ± 1°C and 50-60% humidity.The rats used for the type 1 theta experiments were deeply anesthetized by pentobarbital sodium (50 mg/kg, i.p.) and then placed into a stereotaxic frame. A pair of staggered electrodes (200 µm stainless steel wires insulated except at cut ends) were chronically implanted in the bilateral hippocampal formation. The deep electrode was directed at the molecular layer of the dentate gyrus (DG), and the surface electrode at the CA1 pyramidal cell layer. Two stainless steel screw electrodes for reference and ground were fixed in the skull above the cerebellum. After 1 week of recovery from surgery, the type 1 theta recordings were carried out. The rats were placed in an open field box (100 × 70 × 33 cm) without a roof, which was painted gray. The hippocampal EEG and the behavioral data in the freely moving rats were recorded and stored simultaneously on a video tape using a video converter system (NEC Sanei) which received the signals from a multichannel amplifier and a CCD camera. Walking was selected as a type 1 theta