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Biomedical subjects

Y Dan

Publications and source records attributed to Y Dan.

At least 19 recordsLinked to original sources
PubMed2006

MTH1, an oxidized purine nucleoside triphosphatase, protects the dopamine neurons from oxidative damage in nucleic acids caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

We previously reported that 8-oxoguanine (8-oxoG) accumulates in the cytoplasm of dopamine neurons in the substantia nigra of patients with Parkinson's disease and the expression of MTH1 carrying an oxidized purine nucleoside triphosphatase activity increases in these neurons, thus suggesting that oxidative damage in nucleic acids is involved in dopamine neuron loss. In the present study, we found that levels of 8-oxoG in cellular DNA and RNA increased in the mouse nigrostriatal system during the tyrosine hydroxylase (TH)-positive dopamine neuron loss induced by the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MTH1-null mice exhibited a greater accumulation of 8-oxoG in mitochondrial DNA accompanied by a more significant decrease in TH and dopamine transporter immunoreactivities in the striatum after MPTP administration, than in wild-type mice. We thus demonstrated that MTH1 protects the dopamine neurons from oxidative damage in the nucleic acids, especially in the mitochondrial DNA of striatal nerve terminals of dopamine neurons.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2001

Stimulus timing-dependent plasticity in cortical processing of orientation.

The relative timing of presynaptic and postsynaptic spikes plays a critical role in activity-induced synaptic modification. Here we examined whether plasticity of orientation selectivity in the visual cortex depends on stimulus timing. Repetitive pairing of visual stimuli at two orientations induced a shift in orientation tuning of cat cortical neurons, with the direction of the shift depending on the temporal order of the pair. Induction of a significant shift required that the interval between the pair fall within +/-40 ms, reminiscent of the temporal window for spike timing-dependent synaptic plasticity. Mirroring the plasticity found in cat visual cortex, similar conditioning also induced a shift in perceived orientation by human subjects, further suggesting functional relevance of this phenomenon. Thus, relative timing of visual stimuli can play a critical role in dynamic modulation of adult cortical function, perhaps through spike timing-dependent synaptic plasticity.

Animals↗
PubMed2001

Motion-induced perceptual extrapolation of blurred visual targets.

In the motion-extrapolation hypothesis, the visual system can extrapolate the instantaneous position of a moving object from its past trajectory. The existence of such a mechanism in human vision has been intensely debated. Here, we show compelling perceptual extrapolation of both first- and second-order moving stimuli, the magnitude of which depends on blurring of the visual target. The spatiotemporal characteristics of the extrapolation can be quantitatively accounted for by a simple model based on temporally biphasic neuronal response, a property widely observed among sensory neurons. Thus, motion-induced perceptual extrapolation exists in human vision, and spatial blurring is an important factor in the interaction between motion and perceptual localization.

Computer Simulation↗
PubMed2001

Use of oolong tea extract staining of soft-tissue specimens in low-vacuum scanning electron microscope with a cooling stage.

For direct observation of the surface structures of soft-tissue specimens, we examined rat tracheal tissue in a low-vacuum scanning electron microscope (SEM) equipped with a cooling stage. In specimens fixed with glutaraldehyde and osmium tetroxide, back-scattered electron images of the surface structure could not be clearly observed in the low-vacuum SEM because of the disruption of fine structures and a low signal-to-noise (S/N) ratio. Processing of the specimens in 70% ethanol resulted in marked shrinkage, in contrast to results when processing in 30% ethanol. To overcome these problems, the trachea was initially fixed in 2.5% glutaraldehyde (0.1 M phosphate buffer pH 7.4), treated with a mixture of 0.2% oolong tea extract (OTE) and 2.5% glutaraldehyde, and postfixed in 1% osmium tetroxide. The sample was immersed in 30% ethanol and examined in a chilled SEM at -10 degrees C. The luminal coutour of the tracheal epithelial cells was clearly observed because of the decrease in shrinkage. Cilia of ciliated cells and microvilli of nonciliated cells were also clearly observed. These specimens also showed a high S/N ratio, thus allowing the observation of samples without the need for complete dehydration, critical-point drying, or metal coating. This OTE-incorporated conductive staining method is simple and rapid, and should prove to be highly useful for rapid SEM analyses of biological specimens.

Animals↗
PubMed2001

Analysis of sensory coding with complex stimuli.

Most high-level sensory neurons have complex, nonlinear response properties; a comprehensive characterization of these properties remains a formidable challenge. Recent studies using complex sensory stimuli combined with linear and nonlinear analyses have provided new insights into the neuronal response properties in various sensory circuits.

Acoustic Stimulation↗
PubMed1999

Reconstruction of natural scenes from ensemble responses in the lateral geniculate nucleus.

A major challenge in studying sensory processing is to understand the meaning of the neural messages encoded in the spiking activity of neurons. From the recorded responses in a sensory circuit, what information can we extract about the outside world? Here we used a linear decoding technique to reconstruct spatiotemporal visual inputs from ensemble responses in the lateral geniculate nucleus (LGN) of the cat. From the activity of 177 cells, we have reconstructed natural scenes with recognizable moving objects. The quality of reconstruction depends on the number of cells. For each point in space, the quality of reconstruction begins to saturate at six to eight pairs of on and off cells, approaching the estimated coverage factor in the LGN of the cat. Thus, complex visual inputs can be reconstructed with a simple decoding algorithm, and these analyses provide a basis for understanding ensemble coding in the early visual pathway.

Algorithms↗
PubMed1998

Coding of visual information by precisely correlated spikes in the lateral geniculate nucleus.

Correlated firing among neurons is widespread in the nervous system. Precisely correlated spiking, occurring on a millisecond time scale, has recently been observed among neurons in the lateral geniculate nucleus with overlapping receptive fields. We have used an information-theoretic analysis to examine the role of these correlations in visual coding. Considerably more information can be extracted from two cells if temporal correlations between them are considered. The percentage increase in information depends on the degree of correlation; the average increase is approximately 20% for strongly correlated pairs. Thus, precise temporal correlation could be used as an additional information channel from thalamus to visual cortex.

Action Potentials↗
PubMed1998

Loss of SDF-1 receptor expression during positive selection in the thymus.

SDF-1 is a member of the CXC chemokines. In contrast to other chemokines that are induced by inflammation, SDF-1 is constitutively produced by stromal cells. In order to investigate the physiological roles of SDF-1, we constructed a fusion protein, SDF-1-Cgamma1, composed from murine SDF-1alpha and the constant region of human IgG. SDF-1-Cgamma1 stained EL-4 T lymphoma cells and the staining was blocked by rhSDF-1beta. The expression levels of SDF-1R altered along with the T cell maturation. Most c-kit+ hematopoietic precursors in fetal liver in gestational day (GD) 14.5 embryo were SDF-1R-, while c-kit+ double-negative (DN) thymocytes in the embryo were positive for SDF-1R. The receptor expression increased along with T cell maturation up to double-positive (DP) cell stage. Interestingly, SDF-1R expression was down-modulated after positive selection; CD69+CD3hi DP and CD3hi single-positive thymocytes were SDF-1R-/lo. Northern blot analysis demonstrated that SDF-1 and CXCR4 mRNAs were abundantly expressed in the thymuses of embryo and adult mice. These results demonstrate that SDF-1R expression is involved in T cell development in the thymus, particularly in positive selection.

Animals↗
PubMed1997

Role of ouabain-like compound in the regulation of transmembrane sodium and potassium gradients in rats.

A major biologically active Na,K-ATPase inhibitor in the mammalian body may be ouabain-like compound. We investigated the potential roles of circulating ouabain-like compound in the regulation of Na+ and K+ homeostasis in terms of Na+ and K+ distribution between the cells and the extracellular fluid (internal balance). First, we developed a population of rats immunized against ouabain to block the action of ouabain-like compound. We measured plasma and intracellular Na+ and K+ concentrations in skeletal muscle and determined Na+ (extracellular-to-intracellular concentration ratio) and K+ (intracellular-to-extracellular concentration ratio) gradients in immune rats. We examined also the ability to respond to hypertonic NaCl load in immune rats. Consistent lower plasma K+ levels and steeper Na+ and K+ gradients were observed in immune rats. K+ handling in response to hypertonic NaCl load was altered, and lower plasma K+ level was maintained in immune rats. Second, we used PST-2238, a newly developed anti-ouabain agent, to block the action of ouabain-like compound and examined its effect on plasma Na+ and K+ concentrations. Chronic administration of PST-2238 significantly lowered plasma K+ levels in rats with subtotal nephrectomy. These findings collectively suggest that ouabain-like compound may determine at least in part the internal Na+ and K+ distribution and the transmembrane cation gradients in vivo in rats.

Androstanols↗
PubMed1996

Voltage-sensitive dye recording using retrogradely transported dye in the chicken spinal cord: staining and signal characteristics.

We describe a novel method for retrogradely labeling specific neuronal populations using voltage-sensitive dyes. Styryl dyes were injected into the ventral roots of the isolated embryonic chick spinal cord. After waiting several hours, the dye labeled motoneurons and autonomic preganglionic neurons. Neuronal cell bodies, dendrites and axons were labeled; we presume that the dye traveled either by retrograde transport or by diffusion within the membrane of the axon to which the dyes were initially applied. Using either a photodiode array or a photomultiplier, fluorescence changes could be recorded from motoneurons following antidromic or synaptic activation. Several characteristics of the fluorescence changes were measured indicating that the signals did indeed reflect changes in the motoneuron membrane potential. The best labeling and optical signals were obtained using the relatively hydrophobic dyes di-8-ANEPPQ and di-12-ANEPEQ. In the great majority of cases these dyes responded with an increase in fluorescence of 1-3% (delta F/F) in response to synaptic or antidromic depolarization of the motoneurons. We anticipate that these techniques should be useful in the mapping of activity patterns and connectivity in neural networks within a defined population of neurons.

Action Potentials↗
PubMed1996

Efficient coding of natural scenes in the lateral geniculate nucleus: experimental test of a computational theory.

A recent computational theory suggests that visual processing in the retina and the lateral geniculate nucleus (LGN) serves to recode information into an efficient form (Atick and Redlich, 1990). Information theoretic analysis showed that the representation of visual information at the level of the photoreceptors is inefficient, primarily attributable to a high degree of spatial and temporal correlation in natural scenes. It was predicted, therefore, that the retina and the LGN should recode this signal into a decorrelated form or, equivalently, into a signal with a "white" spatial and temporal power spectrum. In the present study, we tested directly the prediction that visual processing at the level of the LGN temporarily whitens the natural visual input. We recorded the responses of individual neurons in the LGN of the cat to natural, time-varying images (movies) and, as a control, to white-noise stimuli. Although there is substantial temporal correlation in natural inputs (Dong and Atick, 1995b), we found that the power spectra of LGN responses were essentially white. Between 3 and 15 Hz, the power of the responses had an average variation of only +/-10.3%. Thus, the signals that the LGN relays to visual cortex are temporarily decorrelated. Furthermore, the responses of X-cells to natural inputs can be well predicted from their responses to white-noise inputs. We therefore conclude that whitening of natural inputs can be explained largely by the linear filtering properties (Enroth-Cugell and Robson, 1966). Our results suggest that the early visual pathway is well adapted for efficient coding of information in the natural visual environment, in agreement with the prediction of the computational theory.

Animals↗
PubMed1996

IL-3 augments TCR-mediated responses of type 2 CD4 T cells.

A subset of type 2, but not type 1, CD4 T cell clones expresses IL-3R and can be stimulated by IL-3. Expression of IL-3R on these type 2 T cell clones is induced by TCR stimulation, and subsequent stimulation by IL-3 augmented the proliferation of and IL-4 production by these cells. This augmented response is inhibited by anti-IL-4 mAb, suggesting the involvement of IL-4 in this response. In place of TCR stimulation, treatment of these type 2 CD4 T cell clones with PMA rendered them responsive to further stimulation of proliferation by IL-3, indicating the cooperation between the IL-3R-elicited signals and PKC-mediated signals in stimulating proliferation. Although the augmentation of the TCR-mediated proliferative response by IL-3 was mainly due to the increased production of IL-4, we also demonstrated the presence of IL-4-independent mechanism mediating the response to IL-3. In situ, we found that splenic T cells could be induced to respond to Il-3 by TCR stimulation. Thus, IL-3 can stimulate a specific population of T cells and influence the immune response.

Adjuvants, Immunologic↗
PubMed1996

Postsynaptic elevation of calcium induces persistent depression of developing neuromuscular synapses.

Synaptic activity is known to modulate neuronal connectivity in the nervous system. At developing Xenopus neuromuscular synapses in culture, repetitive postsynaptic application of ACh near the synapse leads to immediate and persistent synaptic depression, which was shown to be caused by reduction of presynaptic evoked transmitter release. However, little depression was found when ACh was applied to the muscle 20 microns or further from the synapse. Fluorescence imaging of cytosolic Ca2+ ([Ca2+]i) showed that each ACh pulse induced a transient elevation of myocyte [Ca2+]i that spread approximately 20 microns. Local photoactivated release of Ca2+ from the caged Ca2+ chelators nitr-5 or nitrophen in the postsynaptic cell was sufficient to induce persistent synaptic depression. These results support a model in which localized Ca2+ influx into the postsynaptic myocyte initiates transsynaptic retrograde modulation of presynaptic secretion mechanisms.

Acetylcholine↗
PubMed1995

Plasticity of developing neuromuscular synapses.

Developing neuromuscular synapses are susceptible to modulation by the presence of synaptic activity and a number of chemical factors originated from either pre- or postsynaptic cells. In vitro studies of functional modulation of synaptic strength by electrical stimulation of pre- and postsynaptic cells suggested an essential role of retrograde interactions at developing synapses.

Animals↗