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C F Hsiao

Publications and source records attributed to C F Hsiao.

At least 19 recordsLinked to original sources
PubMed2001

Genetic variation in aldosterone synthase predicts plasma glucose levels.

The mineralocorticoid hormone, aldosterone, is known to play a role in sodium homeostasis. We serendipitously found, however, highly significant association between single-nucleotide polymorphisms in the aldosterone synthase gene and plasma glucose levels in a large population of Chinese and Japanese origin. Two polymorphisms--one in the putative promoter (T-344C) and another resulting in a lysine/arginine substitution at amino acid 173, which are in complete linkage disequilibrium in this population--were associated with fasting plasma glucose levels (P = 0.000017) and those 60 (P = 0.017) and 120 (P = 0.0019) min after an oral glucose challenge. A C/T variant in intron 1, between these polymorphisms, was not associated with glucose levels. Arg-173 and -344C homozygotes were most likely to be diabetic [odds ratio 2.51; 95% confidence interval (C.I.) 1.39-3.92; P = 0.0015] and have impaired fasting glucose levels (odds ratio 3.53; 95% C.I. 2.02-5.5; P = 0.0000036). These results suggest a new role for aldosterone in glucose homeostasis.

Adult↗
PubMed2001

Membrane resonance and subthreshold membrane oscillations in mesencephalic V neurons: participants in burst generation.

Trigeminal mesencephalic (Mes V) neurons are critical components of the circuits controlling oral-motor activity. The possibility that they can function as interneurons necessitates a detailed understanding of the factors controlling their soma excitability. Using whole-cell patch-clamp recording, in vitro, we investigated the development of the ionic mechanisms responsible for the previously described subthreshold membrane oscillations and rhythmical burst discharge in Mes V neurons from rats ages postnatal day (P) 2-12. We found that the oscillation amplitude and frequency increased during development, whereas bursting emerged after P6. Furthermore, when bursting was initiated, the spike frequency was largely determined by the oscillation frequency. Frequency domain analysis indicated that these oscillations emerged from the voltage-dependent resonant properties of Mes V neurons. Low doses of 4-aminopyridine (<100 microm) reduced the oscillations and abolished resonance in most neurons, suggesting that the resonant current is a steady-state K(+) current (I(4-AP)). Sodium ion replacement or TTX reduced substantially the oscillations and peak amplitude of the resonance, suggesting the presence of a persistent Na(+) current (I(NaP)) that functions to amplify the resonance and facilitate the emergence of subthreshold oscillations and bursting.

4-Aminopyridine↗
PubMed2001

High-throughput genotyping with single nucleotide polymorphisms.

To make large-scale association studies a reality, automated high-throughput methods for genotyping with single-nucleotide polymorphisms (SNPs) are needed. We describe PCR conditions that permit the use of the TaqMan or 5' nuclease allelic discrimination assay for typing large numbers of individuals with any SNP and computational methods that allow genotypes to be assigned automatically. To demonstrate the utility of these methods, we typed >1600 individuals for a G-to-T transversion that results in a glutamate-to-aspartate substitution at position 298 in the endothelial nitric oxide synthase gene, and a G/C polymorphism (newly identified in our laboratory) in intron 8 of the 11-beta hydroxylase gene. The genotyping method is accurate-we estimate an error rate of fewer than 1 in 2000 genotypes, rapid-with five 96-well PCR machines, one fluorescent reader, and no automated pipetting, over one thousand genotypes can be generated by one person in one day, and flexible-a new SNP can be tested for association in less than one week. Indeed, large-scale genotyping has been accomplished for 23 other SNPs in 13 different genes using this method. In addition, we identified three "pseudo-SNPs" (WIAF1161, WIAF2566, and WIAF335) that are probably a result of duplication.

Alleles↗
PubMed1999

Outward currents influencing bursting dynamics in guinea pig trigeminal motoneurons.

To initiate and maintain bursts (and plateau potentials) in the presence of serotonin, guinea pig trigeminal motoneurons utilize L-type Ca2+ and persistent Na+ inward currents. However, the intrinsic currents that contribute to burst termination and determine the duration of the interburst interval are unknown. Therefore we investigated the roles of outward currents, whose slow activation is coupled to cytosolic cation (Ca2+ and Na+) accumulation. First we examined a Ca2+-dependent K+ current (IK-Ca) with apamin and Ba2+-substituted, low-Ca2+ solution. Blockade of IK-Ca lengthened burst duration and cycle time but did not abolish bursting. Next we studied the Na+/K+-ATPase pump current (Ip) with cardiac glycosides. In the presence of apamin or low-Ca2+/Ba2+ solution, blocking Ip (with ouabain or strophanthidin) decreased both burst duration and cycle time and ultimately transformed bursting into tonic spiking. We conclude that IK-Ca and Ip contribute to burst termination in trigeminal motoneurons. These currents influence temporal bursting properties such as burst duration and cycle time and may help determine the phasic activity of motoneurons during rhythmic oral-motor behaviors.

Action Potentials↗
PubMed1998

Evidence for a novel bursting mechanism in rodent trigeminal neurons.

We investigated bursting behavior in rodent trigeminal neurons. The essential mechanisms operating in the biological systems were determined based on testable predictions of mathematical models. Bursting activity in trigeminal motoneurons is consistent with a traditional mechanism employing a region of negative slope resistance in the steady-state current-voltage relationship (Smith, T. G. 1975. Nature. 253:450-452). However, the bursting dynamics of trigeminal interneurons is inconsistent with the traditional mechanisms, and is far more effectively explained by a new model of bursting that exploits the unique stability properties associated with spike threshold (Baer, S. M., T. Erneux, and J. Rinzel. 1989. SIAM J. Appl. Math. 49:55-71).

Action Potentials↗
PubMed1998

Ionic basis for serotonin-induced bistable membrane properties in guinea pig trigeminal motoneurons.

Intracellular recordings and pharmacological manipulations were employed to investigate the ionic basis for serotonin-induced bistable membrane behaviors in guinea pig trigeminal motoneurons (TMNs). In voltage clamp, 10 microM serotonin (5-HT) induced a region of negative slope resistance (NSR) in the steady-state current-voltage (I-V) relationship at potentials less negative than -58 mV, creating the necessary conditions for membrane bistability. The contributions of sustained Na+ and Ca2+ currents to the generation of the NSR were investigated using specific ion channel antagonists and agonists. The NSR was eliminated by the L-type Ca2+ channel antagonist nifedipine (5-10 microM), indicating the contribution of L channels. In nifedipine, inward rectification was present in the I-V relationship in a similar voltage range (greater than -58 mV). This region was subsequently linearized by tetrodotoxin (TTX), indicating the presence of a persistent Na+ current. When the 5-HT-induced NSR was eliminated by perfusion in low Ca2+ solution (0.4 mM), it was restored by the Na+ channel agonist veratridine (10 microM). Commensurate with bistability, in current clamp during bath application of 5-HT, plateau potentials were elicited by transient depolarizing or hyperpolarizing stimuli. Plateau potentials evoked by depolarization were observed under control and TTX conditions, but were blocked by nifedipine, suggesting the participation of an L-type Ca2+ current. Plateau potentials initiated after release from hyperpolarization (anode break) were blocked by 300 microM Ni2+, suggesting the responses relied on deinactivation of a T-type Ca2+ current. Conditional bursting was also observed in 5-HT. Nifedipine or low Ca2+ solutions blocked bursting, and the L-channel agonist Bay K 8644 (10 microM) extended the duration of individual bursts, demonstrating the role of L-type Ca2+ currents. Interestingly, when bursting was blocked by nifedipine or low Ca2+, it could be restored by veratridine application via enhancement of the persistent Na+ current. We conclude that bistable membrane behaviors in TMNs are mediated by L-type Ca2+ and persistent Na+ currents. 5-HT is associated with enhancement of TMN activity during oral-motor activity; the induction of bistable membrane properties by 5-HT represents a cellular mechanism for this enhancement.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1997

Multiple effects of serotonin on membrane properties of trigeminal motoneurons in vitro.

Intracellular recordings from guinea pig trigeminal motoneurons (TMNs) in brain stem slices were used to determine the underlying ionic mechanisms responsible for our previously demonstrated enhancement of TMN excitability during jaw movements by serotonin (5-HT). 5-HT (0.5-100 microM) depolarized motoneurons and increased input resistance in the majority of neurons tested. Additionally, 5-HT reduced the amplitude of the postspike medium-duration afterhyperpolarization, decreased the current threshold for maintained spike discharge, and increased the maximum slope of the steady-state spike frequency-current relationship. Under voltage clamp, from holding potentials close to resting potential, 5-HT produced an inward current and a decrease in instantaneous slope conductance, suggesting a reduction in a resting K+ leak conductance (I(leak)). The instantaneous current-voltage (I-V) relationship for the inward 5-HT current (I(5-HT)) was linear throughout most of the voltage range tested. However, the steady-state I-V relationship showed some degree of inward rectification at potentials starting around -70 mV. The mean reversal potential for the instantaneous I(5-HT) was -86.2 +/- 4.5 (SE) mV (n = 9), a value slightly negative to the predicted potassium equilibrium potential of -82 mV in these neurons. In the presence of 2 mM Ba2+, 5-HT application did not produce a further reduction in input conductance, but did expose a Ba2+-insensitive residual inward current that was resistant to Cs+ application. The instantaneous I-V relationship during 5-HT application in the presence of Ba2+ was shifted downward and parallel to control, suggesting that Ba2+ and 5-HT block the same resting I(leak). The residual Ba2+- and Cs+-insensitive component of the total inward I(5-HT) was voltage independent and was blocked when the extracellular Na+ was replaced by choline, suggesting that the predominant charge carrier for this residual current is Na+. 5-HT enhanced a hyperpolarization-activated cationic current, I(h). In the presence of Ba2+, the time course of I(5-HT) resembled that of I(h) and showed a similar voltage dependence that was blocked by extracellular Cs+ (1-3 mM). The effects of 5-HT on membrane potential, input resistance, and I(h) were partially mimicked by 5-HT2 agonists and suppressed by 5-HT2 antagonists. It is concluded that 5-HT enhances TMN membrane excitability through modulation of multiple intrinsic membrane conductances. This provides for a mechanism(s) to fine tune the input-output discharge properties of these neurons, thus providing them with greater flexibility in output in response to time-varying synaptic inputs during various movements of the jaw.

Animals↗
PubMed1995

Characteristics of a fast transient outward current in guinea pig trigeminal motoneurons.

A fast transient voltage dependent outward current (TOC) in trigeminal motoneurons (TMNs) was studied in guinea pig brainstem slices by use of sharp electrodes in combination with single electrode voltage clamp techniques. In solutions containing TTX, low Ca2+/Mn2+ and 20 mM TEA this current activated around -55 to -60 mV from holding potentials negative to resting potential, obtained its peak amplitude within 5 ms and decayed as a single exponential with a time constant of 6-8 ms. Half maximal values for inactivation and activation were -72 and -37 mV, respectively. Bath application of 5 mM 4-AP suppressed this current by approximately 90% and eliminated the early depolarizing transient membrane rectification observed in response to a constant depolarizing current pulse, prolonged the action potential duration, and reduced the threshold voltage and delay to onset of the action potential. It is suggested that this current resembles the typical A-current observed in many CNS neurons and, as a result of its voltage and time dependent properties, could contribute to control of motoneuronal discharge and timing of burst onset during rhythmical jaw movements. Therefore, any cellular models of masticatory activity should include the properties of this current.

4-Aminopyridine↗
PubMed1993

Identification of cell types from action potential waveforms: cerebellar granule cells.

We have recorded 404 single units extracellularly in the cerebellar cortex of the rat with tungsten microelectrodes. Waveforms of action potentials were analyzed in order to develop criteria for on-line identification of cell types. Two of the four most frequently recorded waveforms were simple and complex spikes from Purkinje cells. The other two originated from granule cells and glomeruli. Presumed granule cells showed biphasic action potentials with half-widths (0.78 +/- 0.14 ms, n = 51) broader than those of the simple spikes of Purkinje cells (0.22 +/- 0.06 ms, n = 54), whereas presumed glomerular potentials had complex action potentials with narrower half-widths (0.14 +/- 0.05 ms, n = 35). The mean inter-spike interval of presumed granule cells (333.3 +/- 195.4 ms, n = 53) was longer than that of Purkinje cells (47.3 +/- 31.8 ms, n = 59) and the presumed glomerular potentials (77.7 +/- 50.8 ms, n = 20). Results were virtually identical from 17 cerebellar units recorded extracellularly in the cat. Intracellular recording and staining of 20 granule cells with HRP-filled microelectrodes provided further support for our assessment. These results suggest that action potentials from granule cells may be identified on-line by waveform.

Action Potentials↗
PubMed1992

Electrophysiology of nitrous oxide on cerebellar granule cells: a single-cell study.

We recorded 18 single cells in the granule cell layer of the cat. Each single cell was screened and identified as a granule cell based on a set of criteria derived from known electrophysiological properties of granule cells. We then monitored the effects of nitrous oxide on the spontaneous activities and the auditory responses of these cells. Nitrous oxide consistently caused a severe inhibition of spontaneous activities as well as responses to sound in these cells. Furthermore, the amplitudes of their action potentials decreased during the inhibition. Three of the 18 cells were subsequently injected intracellularly with HRP. All three were verified to be granule cells. In those granule cells we recorded intracellularly, nitrous oxide did not change the resting membrane potentials. The gradual decrease in the amplitudes of action potentials suggested that some of the mechanisms leading to the genesis of action potentials were being altered by nitrous oxide. It is also possible that nitrous oxide may act on synaptic transmission at a site located postsynaptically on the granule cells.

Acoustic Stimulation↗
PubMed1991

Nitrous oxide inhibits auditory and visual responses of granule cells in the cerebellum.

Much of the laboratory investigation on the auditory and visual areas of the posterior vermis has been carried out under barbiturate anesthesia. It is now known that barbiturates potentiate GABA inhibition by binding directly to the GABA receptor protein. Since GABAergic receptors are present in many cell types of the cerebellar cortex, barbiturate anesthesia is likely to interfere severely with cerebellar physiology. We have examined auditory and visual responses in granule cells in the cerebellum of the cat under nitrous oxide anesthesia. To our surprise, nitrous oxide abolished auditory as well as visual responses in the granule cell layer in the posterior vermis. However, both auditory and visual responses recovered after the cessation of nitrous oxide.

Acoustic Stimulation↗
PubMed1991

Auditory receptive area in the cerebellar hemisphere is surrounded by somatosensory areas.

We mapped the neuronal discharges in response to sound in the granule cell layer of the cerebellar hemisphere of the rat. An auditory receptive area was located in the lateral part of Crus IIb. The size of the auditory area was approx. 1 mm2. It was surrounded by somatosensory receptive areas representing the regions in and around the mouth, particularly the lips, the incisors, and areas inside the mouth. Frequency selectivity of neurons in the auditory area was so broad that it resembled the audiogram of the ear of the animal. The auditory responses were not particularly sensitive to binaural intensity differences. On the basis of the response properties of these neurons to sound and the receptive field properties of the adjacent somatosensory areas, we suggest that the function of the auditory area in the cerebellar hemisphere may be in the control of movements involved in vocalization.

Animals↗
PubMed1988

Two types of thalamic reticular cells in relation to the two visual thalamocortical systems in the rat.

We found in urethane-anesthetized rats that thalamic reticular (TR) cells responding to an electrical stimulus of the optic tract (OT) can be further subdivided into two types, viz. S- and L-type cells. S-type cells, which were selectively excited from area 17 of the visual cortex, were characterized by short latency responses (2.3-6.1 ms) to OT stimulation. TR cells activated antidromically from the dorsal lateral geniculate nucleus were all classified as S-type. Long OT latencies (5.2-15.3 ms) and selective excitation from area 18a were peculiar to L-type cells, which showed antidromic responses to the lateral posterior nucleus stimulation. Mapping studies documented that cells belonging to each type were segregated in the thalamic reticular nucleus; L-type cells were located in the most posterior part. It is suggested that S- and L-type cells are inhibitory interneurons modulating activity of geniculocortical and extrageniculocortical projection cells, respectively.

Animals↗
PubMed1986

Alpha and beta cells projecting from retina to lamina A of the lateral geniculate nucleus in normal cats, monocularly deprived cats, and young kittens.

We strictly limited small injection of horseradish peroxidase (HRP) to lamina A of the lateral geniculate nucleus of cats. This was done to label retrogradely only the alpha (Y) and beta (X) classes of retinal ganglion cell. Eighty-six such injections at a range of matched eccentricities were made bilaterally in 9 normal adult cats, 7 cats reared from birth to adulthood with monocular lid suture, and 9 normal kittens at 4 weeks of age; 5348 alpha and beta cells were retrogradely labeled from these injections. Quantitative measurements were made from these labeled cells and compared among 4 experimental conditions, these being normal adult retinas, the nondeprived and deprived retinas of lid sutured cats, and the retinas of kittens. Each injection led to a similar relative ratio of labeled alpha and beta cells (typically 5-15% alpha cells) that did not differ significantly among the experimental conditions, but further analysis suggested a slight diminution of labeled alpha cells in deprived retinas. Because the larger arbors of retinogeniculate Y axons are more likely to penetrate small geniculate HRP injection sites from eccentric locations than would be the case for the more restricted arbors of X axons, a normal tendency resulted for the peripheral halo of zones of retrograde labeling to be dominated by alpha cells. Thus a more accurate reflection of the relative numbers of labeled alpha and beta cells would result from considering only the core of zones of retrograde labeling. When this is done, deprived retinas exhibited relatively fewer labeled alpha cells than did normal, nondeprived, or kitten retinas. This may relate to prior observations (Sur et al. 1982) that abnormally few Y axons from the deprived retina innervate lamina A. No statistically significant differences in alpha or beta cell size were seen among normal, nondeprived, and deprived retinas, although both of these cell types in the kittens were equally smaller than their normal adult counterparts. This is particularly interesting in view of the postnatal growth of retinogeniculate axon arbors (Sur et al. 1984). The results are not surprising for alpha cells, since retinogeniculate Y axon arbors grow considerably after 4 weeks of age, but they are surprising for beta cells, since retinogeniculate arbors of X axons decrease after 4 weeks of age. This suggests no clear, general relationship between soma size and the extent of a cell's axonal arbor.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

Electron microscopic analysis of amacrine and bipolar cell inputs on Y-, X-, and W-cells in the cat retina.

In the cat retina, bipolar and amacrine cell inputs were analyzed electron microscopically in 5 ganglion cells (two Y-cells, two X-cells and one W-cell) that were well-isolated and had clear morphological features. For Y- and X-cells, subtypes of a and b were further identified according to the sublamina of the inner plexiform layer in which their dendrites extended. Y-a and Y-b ganglion cells had large somas, thick axons, and several thick dendrites that branched extensively with a large dendritic field. X-a and X-b cells had medium-sized somas, medium-sized axons and extremely narrow dendritic fields. The W-cell studied had a medium-sized soma, a medium-sized axon, and extremely thin dendrites that extended widely. For each of the 5 ganglion cells, ultrathin serial sections were made to study relative occurrence of amacrine and bipolar synapses in whole length of dendrites. About 50% of the terminals were bipolar in the Y-a and Y-b cell dendrites, 36-38% in the X-a and X-b cell dendrites, whereas only 19.7% were bipolar in the W cell dendrites. Bipolar terminals tended to make synaptic contacts with the distal dendrites of Y- and W-cells.

Animals↗
PubMed1985

Morphological correlates of Y, X and W type ganglion cells in the cat's retina.

After physiological recordings with microelectrodes containing horseradish peroxidase (HRP), morphological properties of Y, X and W type ganglion cells were studied on flat-mounted cat's retinas. While all the Y cells (N = 9) and the X cells (N = 8) revealed alpha and beta cell morphologies of Boycott and Wässle [J. Physiol. 240, 397-419 (1974)], respectively, W cells (N = 4) revealed various morphological types including their gamma and delta cells. The Y cells were larger than X cells in soma diameter, but the W cells were of the same range as X cells. Electron microscopic observations of the cross-sectioned nerve fiber bundles provided evidence for the segregation of axon diameters into the three groups corresponding to Y, X and W axons. It was discussed that functional trichotomy of retinal ganglion cells is related to the differentiation more in axon diameter rather than in soma size.

Action Potentials↗