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At least 1,279 records · Page 71Linked to original sources
PubMed2004

A titania nanotube-array room-temperature sensor for selective detection of hydrogen at low concentrations.

A tremendous variation in electrical resistance, from the semiconductor to metallic range, has been observed in titania nanotube arrays at room temperature, approximately 25 degrees C, in the presence of < or = 1000 ppm hydrogen gas. The nanotube arrays are fabricated by anodizing titanium foil in an aqueous electrolyte solution containing hydrofluoric acid and acetic acid. Subsequently, the arrays are coated with a 10 nm layer of palladium by evaporation. Electrical contacts are made by sputtering a 2 mm diameter platinum disk atop the Pd-coated nanotube array. These sensors exhibit a resistance variation of the order of 10(4) in the presence of 100 ppm hydrogen at 25 degrees C. The sensors demonstrate complete reversibility, repeatability, high selectivity, negligible drift and wide dynamic range. The nanoscale geometry of the nanotubes, in particular the points of tube-to-tube contact, is believed to be responsible for the outstanding hydrogen gas sensitivities.

Acetic Acid↗
PubMedDate not supplied

Determination of morantel-related residues in bovine milk by electron capture gas chromatography.

A gas chromatographic assay was developed to determine major residues of morantel in bovine milk over a range that is suitable for monitoring residues of the drug. The method is based on hydrolysis of the N-methyl-tetrahydropyrimidine portion of morantel and its metabolites to N-methyl-1,3-propanediamine, and converting the diamine to an N,N-bis-(2-nitro-4-trifluoromethylphenyl) derivative. The addition of an internal standard, the N-desmethyl-N-ethyl homolog of pyrantel, to the milk sample circumvents any potential problem that could arise from variable reaction yields, and eliminates the true recovery as a factor affecting the accuracy and precision of the procedure. The concentrations of the derivatives are determined by pulsed electron capture gas chromatography over a linear dynamic range that is equivalent to 12.5-50 ppb morantel. The method was evaluated at the 0, 12.5, 25, and 50 ppb levels in fortified bovine milk, and in a withdrawal sample containing physiologically incurred morantel residues. Mean values of 14 +/- 1.7, 24 +/- 3.7, and 47 +/- 6.9 were found for the fortified samples, approximately 3 ppb for control milk, and 16 +/- 1.7 ppb for the withdrawal sample.

Animals↗
PubMed2006

Responses of excitatory hippocampal synapses to natural stimulus patterns reveal a decrease in short-term facilitation and increase in short-term depression during postnatal development.

Schaffer collateral excitatory synapses onto CA1 pyramidal cells are subject to significant modulation by short-term plasticity. This presynaptic, history-dependent modulation of neurotransmitter release causes synaptic transmission to be sensitive to the frequency of the input. As a result, temporally irregular input patterns, such as those observed in vivo, produce synaptic responses over a very wide dynamic range that reflect a balance of short-term facilitation and short-term depression. The neonatal period is an important developmental period in the hippocampus, when functional representations of an animal's environment are being established through exploratory behavior. The strength of excitatory synapses and their modulation by short-term plasticity are critical to this process. One form of short-term plasticity, paired-pulse facilitation, has been shown to decrease as juvenile rats mature into young adults. However, little is known about the neonatal modulation of other forms of short-term plasticity, including the responses to temporally complex stimuli. We examined developmental modulation of the short-term dynamics of Schaffer collateral excitatory synapses onto CA1 pyramidal cells in acute hippocampal slices, using both constant frequency stimuli and natural stimulus patterns that were taken from in vivo recording of spike patterns of hippocampal cells. In response to constant frequency stimulation, synapses in slices from young adult rats (P28-P35) showed less short-term depression than did those in slices from juveniles (P12-P18). However, when the natural stimulus pattern (containing a wide mix of frequencies) was used, synapses from young adults instead showed more short-term depression and less short-term facilitation than did juveniles. Comparing the natural stimulus pattern responses with constant frequency stimulation of a similar frequency, we found that the average responses were similar in young adults (both showed modest depression). However, in juveniles, the natural pattern produced robust facilitation while constant frequency stimulation caused a large short-term depression. Our results reveal that there are developmental changes both in individual forms of short-term plasticity and in the relative balance between short-term facilitation and short-term depression that will alter the signal transfer characteristics of these synapses.

Animals↗
PubMedDate not supplied

Effects of age, sex and stimulus parameters upon vestibulo-ocular responses to sinusoidal rotation.

We evaluated the vestibulo-ocular reflex (VOR) in 50 normal human subjects, uniformly distributed in age 20-59 years, and evenly distributed in sex by decade, using sinusoidal rotation over the frequency range of 0.005 to 1.0 Hz and three peak amplitudes of 25, 50, and 100 deg/sec. Age variations. The gain magnitude of the normal human VOR appears to decrease with increasing age. This trend becomes statistically significant at p less than 0.05 for the 0.005 and 0.01 Hz test points. Sex-related variations. There were no statistically significant differences in gain magnitude between the sexes but females had higher average gains than males for the lowest test frequencies. The phase data showed a trend with the average phase points for females being less than those for males. This difference was statistically significant at p less than 0.05 for the 0.005 Hz test frequency. Dynamic range. Increasing the stimulus amplitude by a factor of four yielded a small but statistically significant decrease in gain magnitude, thus suggesting a mild saturation-type of nonlinearity.

Adolescent↗
PubMed2005

Dynamic modulations on intensity sensitivity evoked by weak noise in the inferior collicular neurons.

In order to explore the possible mechanisms by which ethologically relevant sounds can be extracted from complex auditory environments, this study examined the effects of weak noise on the rate-intensity functions (RIFs) of neurons responding to tone burst in the inferior colliculus (IC) of nine mice (Mus musculus Km). Under free field stimuli conditions, a total of 112 IC neurons were recorded. RIFs with and without simultaneous presentation of weak noise, of which the intensity was relative to 5 dB below minimum threshold of tone burst, were measured in 44 IC neurons. By means of evaluating the changes of dynamic range (DR), slope of RIFs, and percent inhibition at different tone burst intensities evoked by the weak noise, three types of variations in RIFs were observed, i. e., inhibition (39/44, 88.6%), facilitation (2/44, 4.6%), and no effectiveness (3/44, 6.8%). Statistical analysis indicated that only inhibitory effect of weak noise was significant (P< 0.001, n = 39). The inhibitory effect of weak noise was greater at lower stimulus intensity of tone burst but decreased significantly with increased stimulus intensity (P< 0.0001, n = 39). In addition, the DR and slope of RIFs became narrower and steeper with weak noise presentation, respectively (P< 0.01, n = 31). The results from the present study suggest that weak noise exerts a dynamic modulatory action on acoustical intensity sensitivity of IC neurons, which possibly leads to a better understanding of neural mechanisms underlying the extraction of sound signals from natural auditory scenes.

Acoustic Stimulation↗
PubMed2006

Real-time PCR assay for detection and quantification of hepatitis B virus genotypes A to G.

The detection and quantification of hepatitis B virus (HBV) DNA play an important role in diagnosing and monitoring HBV infection as well as assessing therapeutic response. The great variability among HBV genotypes and the enormous range of clinical HBV DNA levels present challenges for PCR-based amplification techniques. In this study, we describe the development, evaluation, and validation of a novel real-time PCR assay designed to provide accurate quantification of DNA from all eight HBV genotypes in patient plasma specimens. A computer algorithm was used to design degenerate real-time PCR primers and probes based upon a large number (n = 340) of full-length genomic sequences including HBV genotypes A to H from Europe, Africa, Asia, and North and South America. Genotype performance was tested and confirmed using 59 genotype A to G specimens from two commercially available worldwide genotype panels. This assay has a dynamic range of at least 8 log(10) without the need for specimen dilution, good clinical intra- and interassay precision, and excellent correlation with the Bayer Diagnostics VERSANT HBV DNA 3.0 (branched DNA) assay (r = 0.93). Probit analysis determined the 95% detection level was 56 IU/ml, corresponding to 11 copies per PCR well. The high sensitivity, wide linear range, good reproducibility, and genotype inclusivity, combined with a small sample volume requirement and low cost, make this novel quantitative HBV real-time PCR assay particularly well suited for application to large clinical and epidemiological studies.

DNA, Viral↗
PubMed2005

Biosensors to measure inositol 1,4,5-trisphosphate concentration in living cells with spatiotemporal resolution.

Phosphoinositides participate in many signaling cascades via phospholipase C stimulation, which hydrolyzes phosphatidylinositol 4,5-bisphosphate, producing second messengers diacylglycerol and inositol 1,4,5-trisphosphate (InsP3). Destructive chemical approaches required to measure [InsP3] limit spatiotemporal understanding of subcellular InsP3 signaling. We constructed novel fluorescence resonance energy transfer-based InsP3 biosensors called FIRE (fluorescent InsP3-responsive element) by fusing plasmids encoding the InsP3-binding domain of InsP3 receptors (types 1-3) between cyan fluorescent protein and yellow fluorescent protein sequences. FIRE was expressed and characterized in COS-1 cells, cultured neonatal cardiac myocytes, and incorporated into an adenoviral vector for expression in adult cardiac ventricular myocytes. FIRE-1 exhibits an approximately 11% increase in the fluorescence ratio (F530/F480) at saturating [InsP3] (apparent K(d) = 31.3 +/- 6.7 nm InsP3). In COS-1 cells, neonatal rat cardiac myocytes and adult cat ventricular myocytes FIRE-1 exhibited comparable dynamic range and a 10% increase in donor (cyan fluorescent protein) fluorescence upon bleach of yellow fluorescent protein, indicative of fluorescence resonance energy transfer. In FIRE-1 expressing ventricular myocytes endothelin-1, phenylephrine, and angiotensin II all produced rapid and spatially resolved increases in [InsP3] using confocal microscopy (with free [InsP3] rising to approximately 30 nm). Local entry of intracellular InsP3 via membrane rupture by a patch pipette (containing InsP3)in myocytes expressing FIRE-1 allowed detailed spatiotemporal monitoring of intracellular InsP3 diffusion. Both endothelin-1-induced and direct InsP3 application (via pipette rupture) revealed that InsP3 diffusion into the nucleus occurs with a delay and blunted rise of [InsP3] versus cytosolic [InsP3]. These new biosensors allow studying InsP3 dynamics at high temporal and spatial resolution that will be powerful in under-standing InsP3 signaling in intact cells.

Age Factors↗
PubMed2004

Unwrapping Hartmann-Shack images from highly aberrated eyes using an iterative B-spline based extrapolation method.

PURPOSE: When the wavefront aberrations of the eye are measured with a Hartmann-Shack (HS) sensor, the resulting spot pattern must be unwrapped, that is, for each lenslet the corresponding spot must be identified. This puts a limitation on the measurable amount of aberrations. To extend the range of an HS sensor, a powerful unwrapping algorithm has been developed. METHODS: The unwrapping algorithm starts by connecting the central HS spots to the central lenslets. It then fits a B-spline function through a least squares estimate to the deviations of the central HS spots. This function is then extrapolated to find the expected locations of HS spots for the unconnected lenslets. The extrapolation is performed gradually in an iterative manner; the closest unconnected lenslets are extrapolated and connected, and then the B-spline function is least squares fitted to all connected HS spots and extrapolated again. RESULTS: Wavefront aberrations from eyes with high aberrations can be successfully unwrapped with the developed algorithm. The dynamic range of a typical HS sensor increases 3.5 to 13 times compared with a simple unwrapping algorithm. CONCLUSIONS: The implemented algorithm is an efficient unwrapping tool and allows the use of lenslets with a low numerical aperture and thus gives a relatively higher accuracy of measurements of the ocular aberrations.

Algorithms↗
PubMed1983

Intensity functions of single unit responses to tone in the medial geniculate body of cat.

Extracellular spike activity was recorded from single units in the medial geniculate body (MGB) of nitrous oxide anaesthetized cats. The responses of 291 units to tone bursts at the characteristic frequency (CF) were studied as a function of stimulus intensity, covering a range from 10 to 100 dB SPL. The proportion of MGB units characterized by a monotonic or a non-monotonic discharge rate--intensity function was 26% and 74%, respectively. In addition, changes of response latency as a function of tone levels were demonstrated to be either monotonic (38% of units) or non-monotonic (62% of units). One third Of MGB units showed a change of response pattern with increasing intensities, in similar proportion towards either prevailing excitatory or inhibitory components. The monotonic units tended to differ from non-monotonic ones in addition to their intensity function by showing shorter response latencies, a higher response probability to broad-band stimuli and simpler response patterns. The mean dynamic range of the monotonic unit population was 60 dB, with thresholds ranging from 10 to 90 dB SPL; most discharge rate--intensity functions did not saturate at sound levels of 100 dB SPL. In the population of non-monotonic units, the 'best' intensity, defined as th intensity giving the strongest response, ranged between 10 and 100 dB SPL. The present results suggest that the intensity could be signaled by the mean firing rate of a restricted population of monotonic units or place coded by the distribution of maximally activated non-monotonic units which are broadly tuned to different intensities.

Acoustic Stimulation↗
PubMed2001

Polymer microspray with an integrated thick-film microelectrode.

A microfabrication process leading to a sheathless electrospray interface for mass spectrometry analysis is described. Photoablation is performed on a polymer substrate, allowing the integration of a thick-film conductive track in a sealed microchannel. High voltage is supplied close to the outlet, through an embedded microelectrode. The microspray is generated directly from the edge of the substrate without any tip addition. The flexibility of this technology provides a wide range of dimensions for the probe and the microelectrode design, including location, shape, and conductive material used. Thanks to the thick-film microelectrode and the hydrophobicity of the polymer, which avoids solution spreading at the outlet, the device has been found to be an efficient ionization source providing a stable MS signal through time. Moreover, the same device can be used several times without failure. The performance of the microspray has been studied in simple infusion mode for proteins and reserpine MS analyses. The detection limit of reserpine was found to be at the picomolar level in full-scan MS mode. It implies also that approximately 500 zmol was read consumed during 3 min of infusion. A dynamic range from pico- to millimolar level is also underlined.

Microelectrodes↗
PubMed1986

Responses of spinothalamic tract cells in the cat cervical spinal cord to innocuous and graded noxious stimuli.

The response properties of spinothalamic tract (STT) cells in the dorsal horn of the cervical spinal cord were examined in chloralose-anesthetized cats. The activity of 56 STT cells located in laminae IV-VI was studied, with most activity isolated in the lateral part of the dorsal horn. The level of background activity in STT cells was low (mean = 1.2 impulses/sec; n = 26). Conduction velocity estimates for STT axons ranged from 9 to 76 m/sec (mean = 38 m/sec; n = 56) and were not correlated with the recording site in the spinal cord. Most cells were antidromically activated from an electrode in the medial part of the posterior group of nuclei in the thalamus. Excitatory receptive fields were ipsilateral to the recording site, and for 38 of 40 neurons were confined to the forelimb. Although receptive fields were often restricted to part of the paw, they did not include glabrous skin. Among 31 cells classified, four groups were identified: low-threshold (LT) cells (13%) responded to pressure and brushing of the skin; high-threshold (HT) cells (13%) responded only to noxious pinching or squeezing of the skin; wide-dynamic-range (WDR) cells (58%) responded to innocuous mechanical stimuli but had a greater response to noxious stimuli; deep (D) cells (16%) responded to manipulation of subcutaneous tissues such as muscle. Heat stimuli 30 sec in duration, in the range of 43-55 degrees C, were applied to the receptive fields of 14 neurons that included representatives from all three groups with cutaneous input. Nine neurons responded to heat with thresholds that ranged from 47 degrees to 55 degrees C (mean = 51 degrees C). The responses of these nine STT cells increased with increasing stimulus intensity in the noxious range. In the cat cervical dorsal horn, STT cells can signal the occurrence of noxious stimuli on the body surface, and, judging by the sizes of their peripheral receptive fields, are capable of signaling precise information about the location of the damage. Furthermore, some cells are able to signal the intensity of a noxious heating pulse.

Animals↗
PubMed2006

Novel design and controls for focused DNA microarrays: applications in quality assurance/control and normalization for the Health Canada ToxArray.

BACKGROUND: Microarray normalizations typically apply methods that assume absence of global transcript shifts, or absence of changes in internal control features such as housekeeping genes. These normalization approaches are not appropriate for focused arrays with small sets of genes where a large portion may be expected to change. Furthermore, many microarrays lack control features that can be used for quality assurance (QA). Here, we describe a novel external control series integrated with a design feature that addresses the above issues. RESULTS: An EC dilution series that involves spike-in of a single concentration of the A. thaliana chlorophyll synthase gene to hybridize against spotted dilutions (0.000015 to 100 microM) of a single complimentary oligonucleotide representing the gene was developed. The EC series is printed in duplicate within each subgrid of the microarray and covers the full range of signal intensities from background to saturation. The design and placement of the series allows for QA examination of frequently encountered problems in hybridization (e.g., uneven hybridizations) and printing (e.g., cross-spot contamination). Additionally, we demonstrate that the series can be integrated with a LOWESS normalization to improve the detection of differential gene expression (improved sensitivity and predictivity) over LOWESS normalization on its own. CONCLUSION: The quality of microarray experiments and the normalization methods used affect the ability to measure accurate changes in gene expression. Novel methods are required for normalization of small focused microarrays, and for incorporating measures of performance and quality. We demonstrate that dilution of oligonucleotides on the microarray itself provides an innovative approach allowing the full dynamic range of the scanner to be covered with a single gene spike-in. The dilution series can be used in a composite normalization to improve detection of differential gene expression and to provide quality control measures.

Animals↗
PubMed1984

A signal processor for a multiple-electrode hearing prosthesis.

A 22-electrode implantable hearing prosthesis uses a wearable speech processor which estimates three speech signal parameters. These are voice pitch, second formant frequency and flattened spectrum amplitude. The signal is monitored continuously for periodicity in the range 80-400 Hz and, if this is present, stimulation occurs at the same rate. Otherwise, as in the case of unvoiced sounds, it occurs at the random rate of fluctuation of the signal envelope. The second formant is obtained by filtering to extract the dominant peak in the midband region and by continuous measurement of the zero crossing rate. The amplitude measured is that of the whole speech spectrum, pre-emphasized by differentiation. The values that are presented to the patient are the parameter estimates immediately prior to the stimulation pulse. Second formant frequency is coded by selection of an appropriate electrode in the cochlea and amplitude by a suitably controlled current. Automatic gain control is used to keep the dynamic range of the amplitude estimate within the 30 dB range of the circuitry.

Cochlear Implants↗
PubMed2005

Statistical evaluation of internal and external mass calibration laws utilized in fourier transform ion cyclotron resonance mass spectrometry.

The statistical evaluation of two common and three new calibration laws utilized in Fourier transform ion cyclotron resonance mass spectrometry are presented. Electrospray ionization was used to prepare a series of mass spectra of ammonium-adducted polypropylene glycol (PPG) with an average molecular weight of 1000 Da. The singly charged PPG-1000 oligomers allowed for the description of a broad range of m/z and abundance values within each mass spectrum. The hexapole accumulation time was varied to afford a range of total ion abundance values of about an order of magnitude. To examine each of the calibration laws, we utilized cross-validation both "within-spectrum" and "between-spectra" for internally and externally calibrated data, respectively. In addition, we used t-statistics to ensure that each calibration coefficient was statistically significant and necessary to accurately describe the variation in the data. In comparison to commonly used calibration laws for internal calibration, our new calibration law based on multiple linear regression offered a 2-fold improvement in mass measurement accuracy (MMA). In comparison to external calibration laws without automatic gain control, our new calibration law using multiple regression improved the MMA by >10-fold; this improvement would increase further as the dynamic range of the measurement increases (e.g., a biological system). For both our internal and external calibration laws, the median MMA was less than 1 part-per-million. Furthermore, we investigate the number of calibrant ions as well as their required m/z range in order to successfully achieve high MMA.

Calibration↗
PubMed2001

Stability of HCV-RNA level and its lack of correlation with disease severity in asymptomatic chronic hepatitis C virus carriers.

This study examines the relationship between HCV-RNA levels and disease severity in 60 individuals with chronic hepatitis C virus infection. HCV-RNA levels were quantified by the branched DNA (bDNA) assay in 445 samples (median: eight samples per patient) obtained over a median of 40.4 months (95% confidence interval (CI): 37.0-42.5). The median log HCV-RNA level was 6.77 (95% CI: 6.62-6.92) molecular equivalents/mL (MEQ/mL). The median log range of HCV-RNA levels in individual patients over the course of the study was 0.89 (95% CI: 0.69-1.16). HCV-RNA level varied over time by less than one log in 62% of patients, by 1-1.5 logs in 22% and by greater than 1.5 logs in only 17%. Univariate analysis, revealed an inverse association between HCV-RNA levels and ALT levels (P=0.037). Univariate and logistic regression analysis showed no significant association between HCV-RNA levels and either the degree of inflammation or fibrosis. In contrast, there was a significant positive association between alanine aminotransferase (ALT) levels and histological activity especially in individuals with ALTs> 100 IU/L. Hence, HCV-RNA levels: (i) almost always fell within the dynamic range of the bDNA assay; (ii) were stable in asymptomatic chronically infected patients, with only a small proportion of patients exceeding a range of 1.5 logs; (iii) did not correlate with either the extent of inflammation or degree of fibrosis. In contrast, there was a strong association between ALT level and the histological severity of liver disease.

Adult↗
PubMed1992

Discharge patterns of cochlear ganglion neurons in the chicken.

Physiological recordings were made of the compound action potential from the round window and single neurons in the cochlear ganglion of normal adult chickens (Gallus domesticus). The compound action potential threshold to tone bursts decreased from approximately 42 dB at 0.25 kHz to 30 dB between 1 and 2 kHz and then increased to 51 dB at 4 kHz. Most of the cochlear ganglion cells had characteristic frequencies below 2 kHz and the thresholds of most neurons were roughly 30-35 dB lower than the compound action potential thresholds. At any given characteristic frequency, thresholds varied by as much as 60 dB and units with the highest thresholds tended to have the lowest spontaneous rates. Spontaneous discharge rates ranged from 0 to 200 spikes/s with a mean rage of 86 spikes/s. Interspike interval histograms of spontaneous activity often contained regular peaks with the time interval between peaks approximately equal to 1/(characteristic frequency). Tuning curves were sharply tuned and V-shaped with approximately equal slopes to the curves above and below characteristic frequency. Q10dB and Q30dB values for the tuning curves increased with characteristic frequency. Post stimulus time histograms showed sustained firing during the stimulus and were characterized by a slight-to-moderate peak at stimulus onset. Most units showed vigorous phase-locking to tones at characteristic frequency although the degree of phase-locking declined sharply with increasing characteristic frequency. Discharge rate-level functions at characteristic frequency had a mean dynamic range of 42 dB and a mean saturation firing rate of 327 spikes/s. In general, the firing patterns of cochlear ganglion neurons are similar in most respects to those reported in other avians, but differ in several important respects from those seen in mammals.

Acoustic Stimulation↗
PubMed2005

Microstructured layers of spherical biofunctional core-shell nanoparticles provide enlarged reactive surfaces for protein microarrays.

Nanostructured core-shell particles with tailor-made affinity surfaces were used to generate microstructured affinity surfaces by microspotting the particles to form densely packed amorphous nanoparticle layers. These layers provided a large reactive surface for the specific binding of protein ligands from aqueous solution. Biofunctional core-shell particles were synthesized for this purpose that consisted of a silica core with a diameter of 100 nm and an organic shell a few nm thick. The nanoparticle core was prepared by sol-gel chemistry and the shell formed in suspension by organosilane chemistry. The shell provided amino groups or carbonyl groups at its outer surface for subsequent covalent immobilization of streptavidin, rabbit IgG antibodies or goat IgG antibodies. AlexaFluor 647-conjugated and biotinylated cytochrome C and CyDye-labeled anti-rabbit IgG and anti-goat IgG were probed as model analytes. The core-shell nanoparticles were spotted using a pin-ring micro-arrayer onto microscope glass slides that were coated with a polycation monolayer by dip-coating prior to nanoparticle deposition. Amorphous particle layers of well-defined thicknesses in the range of 100 nm to 2 microm were obtained by printing aqueous particle suspensions containing 5-500 mg/mL (0.5-50 wt%) of silica particles. The specific affinity of the plotted nanoparticulate capture surface was demonstrated by binding Cy3-labeled donkey anti-rabbit IgG and Cy5-labeled mouse anti-goat IgG to immobilized rabbit IgG and goat IgG particles. The signal intensity per spot increased for any given analyte concentration when the amount of particles per spot was augmented. This was attributed to the increasing integration of receptor molecules per surface footprint, which shifted the binding equilibrium towards the formation of the receptor-ligand complex. Additionally, the locally-increased supply of receptor molecules at the nanoparticulate microchip surface resulted in a wide dynamic range of 4 fM-20 nM (covering six orders of magnitude).

Adsorption↗
PubMed2005

Dynamic dopamine modulation in the basal ganglia: a neurocomputational account of cognitive deficits in medicated and nonmedicated Parkinsonism.

Dopamine (DA) depletion in the basal ganglia (BG) of Parkinson's patients gives rise to both frontal-like and implicit learning impairments. Dopaminergic medication alleviates some cognitive deficits but impairs those that depend on intact areas of the BG, apparently due to DA ''overdose.'' These findings are difficult to accommodate with verbal theories of BG/DA function, owing to complexity of system dynamics: DA dynamically modulates function in the BG, which is itself a modulatory system. This article presents a neural network model that instantiates key biological properties and provides insight into the underlying role of DA in the BG during learning and execution of cognitive tasks. Specifically, the BG modulates the execution of ''actions'' (e.g., motor different parts of the frontal cortex. Phasic changes in DA, which occur during error feedback, dynamically modulate the BG threshold for facilitating/suppressing a cortical command in response to particular stimuli. Reduced dynamic range of DA explains Parkinson and DA overdose deficits with a single underlying dysfunction, despite overall differences in raw DA levels. Simulated Parkinsonism and medication effects provide a theoretical basis for behavioral data in probabilistic classification and reversal tasks. The model also provides novel testable predictions for neuropsychological and pharmacological studies, and motivates further investigation of BG/DA interactions with the prefrontal cortex in working memory.

Basal Ganglia↗