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Nanoliter high throughput quantitative PCR.

Understanding biological complexity arising from patterns of gene expression requires accurate and precise measurement of RNA levels across large numbers of genes simultaneously. Real time PCR (RT-PCR) in a microtiter plate is the preferred method for quantitative transcriptional analysis but scaling RT-PCR to higher throughputs in this fluidic format is intrinsically limited by cost and logistic considerations. Hybridization microarrays measure the transcription of many thousands of genes simultaneously yet are limited by low sensitivity, dynamic range, accuracy and sample throughput. The hybrid approach described here combines the superior accuracy, precision and dynamic range of RT-PCR with the parallelism of a microarray in an array of 3072 real time, 33 nl polymerase chain reactions (RT-PCRs) the size of a microscope slide. RT-PCR is demonstrated with an accuracy and precision equivalent to the same assay in a 384-well microplate but in a 64-fold smaller reaction volume, a 24-fold higher analytical throughput and a workflow compatible with standard microplate protocols.

Cells, Cultured↗

A novel, high-performance random array platform for quantitative gene expression profiling.

We have developed a new microarray technology for quantitative gene-expression profiling on the basis of randomly assembled arrays of beads. Each bead carries a gene-specific probe sequence. There are multiple copies of each sequence-specific bead in an array, which contributes to measurement precision and reliability. We optimized the system for specific and sensitive analysis of mammalian RNA, and using RNA controls of defined concentration, obtained the following estimates of system performance: specificity of 1:250,000 in mammalian poly(A(+)) mRNA; limit of detection 0.13 pM; dynamic range 3.2 logs; and sufficient precision to detect 1.3-fold differences with 95% confidence within the dynamic range. Measurements of expression differences between human brain and liver were validated by concordance with quantitative real-time PCR (R(2) = 0.98 for log-transformed ratios, and slope of the best-fit line = 1.04, for 20 genes). Quantitative performance was further verified using a mouse B- and T-cell model system. We found published reports of B- or T-cell-specific expression for 42 of 59 genes that showed the greatest differential expression between B- and T-cells in our system. All of the literature observations were concordant with our results. Our experiments were carried out on a 96-array matrix system that requires only 100 ng of input RNA and uses standard microtiter plates to process samples in parallel. Our technology has advantages for analyzing multiple samples, is scalable to all known genes in a genome, and is flexible, allowing the use of standard or custom probes in an array.

Animals↗

Determination of tumor necrosis factor-alpha (TNF-alpha) in serum by a highly sensitive enzyme amplified lanthanide luminescence immunoassay.

OBJECTIVES: To develop a highly sensitive enzyme amplified lanthanide luminescence (EALL) immunoassay for tumor necrosis factor-alpha (TNF-alpha). METHODS: The method is based on the use of two monoclonal antibodies against TNF-alpha, one "capture" antibody and one labeled with biotin, in a "sandwich type" assay format. Alkaline phosphatase (ALP) conjugated to an antibiotin-polyclonal antibody is used as the enzyme label. ALP cleaves phosphate from diflunisal phosphate (DIFP) to produce diflunisal (DIF). The detection system is based on the combination of enzymatic amplification introduced by ALP and the formation of a highly fluorescent terbium complex that can be monitored by time resolved or conventional fluorimetry. RESULTS: By using 50 microL of sample, the dynamic range of the assay extends up to 2000 ng/L of TNF-alpha, with a detection limit of 1 ng/L, within-run CVs ranging from 3 to 15% and recoveries of 97 +/- 2%. By using 100 microL of sample the dynamic range of the assay extends up to 1000 ng/L of TNF-alpha with a detection limit of 0.2 ng/L, recoveries of 94 +/- 13%, within-run CVs ranging from 2 to 6.5% and between-run CVs ranging from 5 to 15%, in a total incubation time of 3h. No interference by the presence of other cytokines (IL-1beta IL-2, IL-4, IL-6, IFN-gamma) or by rheumatoid factors has been observed. The results obtained by the proposed method and by a commercially available kit (Medgenix TNF-alpha EASIA) correlated well (n = 26, r = 0.934). CONCLUSION: The proposed method is highly sensitive, simple and rapid and can reliably measure TNF-alpha in the ng range in biological specimens.

Enzyme-Linked Immunosorbent Assay↗

Separation of uranium(VI) and transition metal ions with 4-(2-thiazolylazo)resorcinol by capillary electrophoresis.

A capillary electrophoresis method utilizing 4-(2-thiazolylazo)resorcinol (TAR) was developed to separate uranium, cobalt, cadmium, nickel, titanium and copper metal ions. TAR was chosen as the visible absorbing chelating ligand because of its ability to form stable complexes with a wide variety of metals. Several parameters that included pH, electrophoretic run buffer concentration, buffer type and the influence of chelating ligand in the electrophoretic run buffer were examined to determine the best separating conditions. Optimum separation of the six metal chelates was achieved in a 15 mM Na2B4O7-NaH2PO4, pH 8.3 buffer containing 0.1 mM TAR. Method validation included injection and method precision studies as well as detection limit and linear dynamic range determination. High-ppb to low-ppm (w/w ratio) detection limits were achieved with linear dynamic ranges between 0.1 and 75 ppm.

Azo Compounds↗

NSAID-induced cyclooxygenase inhibition differentially depresses long-lasting versus brief synaptically-elicited responses of rat spinal dorsal horn neurons in vivo.

This electrophysiological study examined the effects of NSAID administration on synaptically-elicited responses of rat single spinal dorsal horn neurons to natural stimulation of peripheral receptive fields. Nociceptive responses consisted of a fast initial discharge during the stimulus followed by a slowly-decaying afterdischarge. The cyclooxygenase inhibitor, indomethacin (2.0-8.0 mg/kg, i.v.), was without effect on the on-going rate of discharge but dose-dependently inhibited synaptically-elicited responses to noxious cutaneous mechanical stimulation (fast initial discharge: n = 3/3 with 2 mg/kg, 5/8 with 4 mg/kg, 5/6 with 8 mg/kg; slowly-decaying afterdischarge: n = 3/3 with 2 mg/kg, 6/8 with 4 mg/kg, 6/6 with 8 mg/kg) and thermal (fast initial discharge: n = 7/9 with 8 mg/kg; slowly-decaying afterdischarge: n = 3/4 with 4 mg/kg, n = 7/9 with 8 mg/kg). The inhibitory effect of indomethacin started within 2-4 min and lasted up to 120 min. To eliminate any effect of indomethacin via cutaneous sensory receptors it was tested on the responses of some neurons to high intensity electrical stimulation of the sciatic nerve; indomethacin depressed these evoked responses (fast initial discharge: n = 5/6 with 2 mg/kg, n = 7/7 with 4 mg/kg; slowly-decaying afterdischarge: n = 6/6 with 2 mg/kg, n = 7/7 with 4 mg/kg). The brief excitatory responses to innocuous pressure (fast initial discharge: n = 2/3 with 2 mg/kg, n = 6/8 with 4 mg/kg, n = 4/6 with 8 mg/kg) and hair (n = 2/7 with 2 and 4 mg/kg, respectively) stimulation in both non-nociceptive and wide dynamic range neurons were also depressed but to a lesser extent. However, the prolonged excitation of three wide dynamic range neurons to continuous hair stimulation was almost entirely inhibited by indomethacin. Overall, inhibition of the afterdischarge and the excitatory effect of long-lasting synaptic input were greater than inhibition of the fast synaptic input-evoked initial discharge. The evidence supports the suggestion that systemically-administered indomethacin has an effect in the spinal cord and demonstrates an action specifically in the dorsal horn. The data are interpreted to suggest that sensory inputs are more involved than input-independent excitation of dorsal horn neurons in leading to de novo synthesis of eicosanoids and that the time course of this synthesis brings the levels to a point where COX inhibition can have an observable effect during prolonged excitation. Although the data suggest that COX inhibition differentially inhibits nociceptive versus non-nociceptive mechanisms at the cellular level, irrespective of the modality of the stimulus, this is the first direct demonstration that prolonged activation of synaptic mechanisms are preferentially inhibited. According to this it would be predictable that NSAIDs would be more effective on nociceptive types of pain characterized by time or prolonged inputs of primary afferents.

Animals↗

Post-column reaction detection based on fluorescence energy transfer in the far red spectral region.

Post-column reaction detection may result in enhanced analytical sensitivity and selectivity. This paper describes an on-line HPLC with post-column fluorescence energy transfer assay using biotin as a model analyte. Biotin labeled with R-phycoerythrin was used as the donor labeled ligand and streptavidin labeled with an indodicarbocyanine dye (Cy5), the acceptor labeled binder protein. The use of these labels provided a detection wavelength in the far red spectral region which is more selective for biological samples. In the on-line system, biotin was injected into the HPLC system followed by Cy5 labeled streptavidin and R-phycoerythrin labeled biotin, post-column. The mixture was incubated on-line in an open tubular reactor coil maintained at 37 degrees C. The measured response was the sensitized emission of Cy5 due to fluorescence energy transfer from R-phycoerythrin labeled biotin measured at 670 nm. Excitation was at 488 nm, which provided a large Stokes shift for reduction of scatter interference. The system was optimized with regard to the post-column reagents to obtain the minimum detectable concentration while maintaining appropriate dynamic range for the analysis of biotin. Biotin spiked in 0.01 M phosphate buffer, pH 7.4, showed a dynamic range of 304.0 pg/ml-122.20 ng/ml with a correlation coefficient of 0.993. The limit of detection for this assay was 304.0 pg/ml. The precision calculated at the blank (n = 6) was 4.14%.

Biotin↗

Comparison of the electroacoustic characteristics of five hearing aids.

This paper describes a comparison of the electroacoustic characteristics of five hearing aids: (1) a linear BTE aid of the type dispensed under the UK National Health Service (NHS), the BE19; (2) an analogue programmable BTE aid incorporating two-channel wide dynamic range compression, the ReSound BT2; (3) and (4) two digital BTE aids incorporating multi-channel wide dynamic range compression, the Phonak Claro and the Danavox Danalogic; (5) a disposable ITE hearing aid with single-channel compression, the Songbird. Measurements of frequency response using a 2 cc coupler showed that the NHS aid had a distinct undesired peak around 1 kHz. The response rolled off at low and high frequencies, and no gain was applied above about 4000 Hz. The BT2 and Claro both showed somewhat irregular responses with effective upper frequency limits of 5000-6000 Hz. The Danalogic had a reasonably smooth response and provided gain up to 6000 Hz. The Songbird had a smooth response and provided gain up to about 7000 Hz. All aids showed reasonably low harmonic and intermodulation distortion (probably below audible levels for hearing-impaired listeners), the Phonak Claro being the best in this respect. Measures of the effective input noise were obtained using two new methods. The NHS aid had the highest (worst) effective input noise, whereas the Songbird had the lowest, especially at low frequencies. The BT2 and the two digital aids had similar noise levels on one measure, but the BT2 was superior on the other measure. The compression circuits were characterized by measuring attack and release times and by using a method described by Stone and Moore (1992). The aids varied markedly in the extent to which they compressed amplitude modulation at the rates typically occurring in speech (2-10 Hz), the Claro providing the least compression and the Danalogic and Songbird aids providing the most. Overall, the results indicate that the NHS aid performed more poorly in several respects than the other aids. There were no great differences in electroacoustic characteristics between the remaining analogue aids and the digital aids, although the Songbird had a somewhat wider frequency range and lower effective input noise than the other aids.

Acoustic Stimulation↗

A stochastic model of the electrically stimulated auditory nerve: pulse-train response.

The single-pulse model of the companion paper [1] is extended to describe responses to pulse trains by introducing a phenomenological refractory mechanism. Comparisons with physiological data from cat auditory nerve fibers are made for pulse rates between 100 and 800 pulses/s. First, it is shown that both the shape and slope of mean discharge rate curves are better predicted by the stochastic model than by the deterministic model. Second, while interpulse effects such as refractory effects do indeed increase the dynamic range at higher pulse rates, both the physiological data and the model indicate that much of the dynamic range for pulse-train stimuli is due to stochastic activity. Third, it is shown that the stochastic model is able to predict the general magnitude and behavior of variance in discharge rate as a function of pulse rate, while the deterministic model predicts no variance at all.

Analysis of Variance↗

Modeling auditory-nerve responses for high sound pressure levels in the normal and impaired auditory periphery.

This paper presents a computational model to simulate normal and impaired auditory-nerve (AN) fiber responses in cats. The model responses match physiological data over a wider dynamic range than previous auditory models. This is achieved by providing two modes of basilar membrane excitation to the inner hair cell (IHC) rather than one. The two modes are generated by two parallel filters, component 1 (C1) and component 2 (C2), and the outputs are subsequently transduced by two separate functions. The responses are then added and passed through the IHC low-pass filter followed by the IHC-AN synapse model and discharge generator. The C1 filter is a narrow-band, chirp filter with the gain and bandwidth controlled by a nonlinear feed-forward control path. This filter is responsible for low and moderate level responses. A linear, static, and broadly tuned C2 filter followed by a nonlinear, inverted and nonrectifying C2 transduction function is critical for producing transition region and high-level effects. Consistent with Kiang's two-factor cancellation hypothesis, the interaction between the two paths produces effects such as the C1/C2 transition and peak splitting in the period histogram. The model responses are consistent with a wide range of physiological data from both normal and impaired ears for stimuli presented at levels spanning the dynamic range of hearing.

Acoustic Stimulation↗

Armored RNA as virus surrogate in a real-time reverse transcriptase PCR assay proficiency panel.

In recent years testing responsibilities for high-consequence pathogens have been expanded from national reference laboratories into networks of local and regional laboratories in order to support enhanced disease surveillance and to test for surge capacity. This movement of testing of select agents and high-consequence pathogens beyond reference laboratories introduces a critical need for standardized, noninfectious surrogates of disease agents for use as training and proficiency test samples. In this study, reverse transcription-PCR assay RNA targets were developed and packaged as armored RNA for use as a noninfectious, quantifiable synthetic substitute for four high-consequence animal pathogens: classical swine fever virus; foot-and-mouth disease virus; vesicular stomatitis virus, New Jersey serogroup; and vesicular stomatitis virus, Indiana serogroup. Armored RNA spiked into oral swab fluid specimens mimicked virus-positive clinical material through all stages of the reverse transcription-PCR testing process, including RNA recovery by four different commercial extraction procedures, reverse transcription, PCR amplification, and real-time detection at target concentrations consistent with the dynamic ranges of the existing real-time PCR assays. The armored RNA concentrations spiked into the oral swab fluid specimens were stable under storage conditions selected to approximate the extremes of time and temperature expected for shipping and handling of proficiency panel samples, including 24 h at 37 degrees C and 2 weeks at temperatures ranging from ambient room temperature to -70 degrees C. The analytic test performance, including the reproducibility over the dynamic range of the assays, indicates that armored RNA can provide a noninfectious, quantifiable, and stable virus surrogate for specific assay training and proficiency test purposes.

Laboratories↗

Characteristics of spinoreticular and spinothalamic neurons with renal input.

Spinoreticular (SRT) and spinothalamic (STT) neurons were studied for responses to renal and somatic stimuli in 34 cats that were anesthetized with alpha-chloralose. SRT cells were antidromically activated from the medial medullary reticular formation near the gigantocellular tegmental field contralateral (35 cells), ipsilateral (15 cells), or both contralateral and ipsilateral (11 cells) to the recording site. Collision tests showed that activation from two electrodes resulted from stimulation of separate axonal branches and not from current spread. Twenty STT cells were activated from the spinothalamic tract just medial to the medial geniculate nucleus. SRT cells were located in laminae I, V, VII, and VIII of the T12-L2 segments. Most cells were located in lamina VII. STT cells were found in laminae I, V, and VII. The axons of 12 SRT cells were located in the ventrolateral or ventral quadrants of the upper cervical spinal cord. Antidromic conduction velocities of SRT cells averaged 48.7 +/- 3.7 m/s. No differences in conduction velocity were found between cells projecting to different reticular sites. In addition conduction velocity did not vary with the type of somatic or renal input. Antidromic conduction velocities of STT cells averaged 46.4 +/- 4.7 m/s. Renal nerve stimulation excited 58 and inhibited 3 SRT cells. All 20 STT cells were excited. Thirty SRT cells were excited only by A-delta input, 26 received both A-delta- and C-fiber inputs, and 2 cells received only C-fiber input. Ten STT cells received A-delta input only and 10 received both A-delta- and C-fiber inputs. All cells with renal input also received somatic input. Thirty-six SRT cells (59%) were classified as high threshold, 12 (20%) as wide dynamic range, and 10 (16%) as deep. Ten STT cells were classified as high threshold and 10 as wide dynamic range. Somatic receptive fields of STT cells were usually simple and invariably included the left flank region, although many of the fields extended to the left hindlimb or abdomen. Eighteen of the 20 were restricted to the ipsilateral side. In contrast, somatic receptive fields of SRT cells were primarily bilateral (71%). While all but two receptive fields included the left flank area, most extended to one or both hindlimbs, the abdomen, or the right flank. Inhibitory receptive fields were found for 33% of the SRT cells and 20% of the STT cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

Non-invasive electrical stimulation of the ear canal as a communication aid in acquired total deafness.

Some profoundly deafened patients, who cannot be helped by sound amplification, claim to perceive auditory sensations when alternating currents up to 100 Hz are passed through electrodes applied to the skin of the external ear canal. A portable speech processor has been developed which supplies this current. The signal is a balanced square wave, the frequency of which is proportional to the first formant frequency. The amplitude is proportional to the intensity of voiced sounds. In order to fit the narrow frequency and dynamic range of the electrical stimulus, the speech processor produces a downward frequency transposition and strong limitation of the dynamic range. The device has been tested for (1) discrimination of environmental sounds; (2) question/statement discrimination; (3) identification of vowels and consonants in vowel/consonant/vowel context; (4) lip-reading with and without the prosthesis.

Adult↗

[Stapedial reflexes in presbyacusis and occupational deafness].

Acoustic reflex thresholds were measured on 251 subjects (418 ears) with varying degrees of sensorineural hearing loss. The subjects are divided in three groups according to the pathology involved: presbyacusis and noise-induced hearing loss and combined hearing loss caused by both presbyacusis and noise exposure. The dynamic range of hearing was found to be reduced for all cases and at all frequencies. The decrease in dynamic range was proportional to the severity of the hearing loss. The sensation levels of the acoustic reflex thresholds seem to be dependent on the degree of hearing loss and not on the aetiology. Practical conclusions are drawn concerning the prediction of thresholds of hearing and the diagnosis of recruitment based on reflex measurements.

Adult↗

Expertise of laboratories in viral load quantification, genotyping, and precore mutant determination for hepatitis B virus in a multicenter study.

A national evaluation study was performed in 14 specialized laboratories with the objective of assessing their capacities to provide (i) hepatitis B virus (HBV) viral loads (VL), (ii) HBV genotypes, and(iii) identification of precore/core mutants. The panel consisted of 12 HBV DNA-positive samples with VLs from 2.8 to 9.1 log(10) copies/ml, different HBV genotypes (A to F), and 3 mutant and 9 wild-type samples at nucleotide 1896. The coefficients of variation of the mean VLs ranged from 2.4% to 10.4% with the Cobas HBV Monitor assay, from 1.8% to 5.5% with the Cobas TaqMan 48, from 1.5 to 26.2% with RealArt HBV PCR, and from 0 to 7% with branched DNA (bDNA). The Cobas Monitor assay underestimated the VLs of genotype F samples, with differences ranging from 1.4 to 2.4 log(10) copies/ml. The accuracies of genotype determinations ranged from 33% to 100%, and those of precore mutant determinations ranged from 25 to 100%. This study showed some drawbacks of two widely used assays: (i) Cobas Monitor has a narrow dynamic range and underestimates genotype F sample VLs and (ii) bDNA shows poor sensitivity and may fail to identify patients with low VLs. With higher performance in terms of analytical sensitivity combined with a larger dynamic range and an ability to quantify the main genotypes equally, real-time PCR methods appear more appropriate for accurate monitoring of HBV DNA quantification. Furthermore, the clinical implications of HBV genotyping and the determination of precore/core mutants need to be clearly stated to justify the standardization of these methods.

France↗

A novel separation-free assay technique for serum antibodies using antibody bridging assay principle and two-photon excitation fluorometry.

A new technique for separation-free detection of antigen-specific antibodies is presented. The new technique employs antibody bridging assay principle and the recently developed ArcDia TPX fluorescence detection technology. According to the assay scheme, antibody molecules from the sample bind with one arm to an antigen on polymer microspheres and with the other arm to a fluorescently labeled secondary antigen reagent. Consequently, fluorescent immunocomplexes are formed on the surface of microspheres in proportion to the concentration of the analyte in the sample. The fluorescence signal from individual microspheres is measured by means of two-photon excited fluorescence detection. In order to demonstrate the applicability of the new assay technique, an assay for anti-adenovirus antibodies was constructed. The function of the assay method was tested both with monoclonal anti-adenovirus antibody preparation (standard analyte), and with positive serum samples. Standard class-specific ELISA was used as a reference method. The new assay method provides comparable sensitivity and precision, and wider dynamic range for IgG antibodies than the ELISA method. The standard curve showed linear response (R(2)=0.999) with a dynamic range of three orders of magnitude, detection limit (mean+3S.D.) of 8 pM, and intra-assay signal precision of 5%. Applicability of the new method for clinical serodiagnostics is discussed.

Animals↗

Optimizing albunex in the left ventricle: an analysis of the technical parameters of four ultrasound systems in canines and humans.

Albunex, an intravascular ultrasound contrast agent, has been used clinically to enhance echocardiographic images. The purpose of this study if (1) to determine whether varying the settings on commercially available ultrasound machines has an effect on left ventricular opacification after intravenously administered Albunex and if there is an effect on left ventricular opacification and (2) to determine the ideal settings for each ultrasound scanner. Six canine hearts were imaged with 1 ml injections of intravenously administered Albunex while varying the transducer frequency, preprocessing curves, postprocessing curves, and dynamic range on a variety of ultrasound units. Subsequently 50 human subjects underwent imaging with the various machines while the dynamic range and transducer frequencies were altered. All subjects received two or three intravenous injections of 10 ml Albunex. The opacification of the left ventricular cavitary images in both parts of the study were interpreted visually on a scale of 0 to 4 (0 = none, 1 = trace, 2 = moderate, 3 = dense, and 4 = ideal) by four observers. The maximum compression and transducer frequency of 3.5 MHz showed significant improvement of left ventricular opacification in both canines and humans. These studies have shown that (1) varying the ultrasound unit's parameters affects the quality of left ventricular imaging when Albunex is used to enhance the image, and (2) higher compression and a transducer frequency of 3.5 MHz tend to enhance Albunex images of canine and human hearts.

Albumins↗

Enkephalin-immunoreactive nociceptive neurons in the cat spinal cord.

In this combined electrophysiological-ultrastructural study in the cat spinal cord, we detected enkephalin-like immunoreactivity using internally radio-labelled monoclonal antibodies in functionally characterized neurons which had been filled intracellularly with horseradish peroxidase. Of the 4 neurons included in this study, two were positive for enkephalin immunoreactivity; one was a nociceptive specific neuron in lamina I, the other a wide dynamic range neuron in lamina V. The other two cells were devoid of immunoreactivity for enkephalin; one was a wide dynamic range neuron and the other was a non-nociceptive neuron. These results thus provide a morphological substrate within the spinal dorsal horn for the release of an endogenous opioid following administration of substance P or noxious cutaneous stimulation.

Animals↗

Single-unit responses in the inferior colliculus: effects of neonatal unilateral cochlear ablation.

Monaural responses of single units isolated in the inferior colliculus of adult gerbils that have developed postnatally with one cochlea were compared with monaural responses recorded in animals that have developed with both cochleas. One cochlea of 2-day-old gerbils was ablated, and at approximately 6 mo of age, excitatory responses to stimulation of the nonoperated ear were recorded in the ipsilateral inferior colliculus. These responses were compared quantitatively with responses evoked by ipsilateral and contralateral monaural stimulation in normal gerbils. Responses to ipsilateral stimulation in adult gerbils subjected at 2 days of age to ablation of the contralateral cochlea are significantly different from ipsilateral responses in nonoperated gerbils. In several respects they are very similar to contralateral responses in nonoperated gerbils. (Differences between monaural contralateral and ipsilateral responses in control animals are documented in the companion paper, Ref. 24.) These conclusions are based on analyses of response threshold, peak discharge rate, response pattern, and minimum response latency. The mean dynamic range of ipsilateral rate/intensity functions obtained in neonatally ablated gerbils is significantly larger than the mean ipsilateral and contralateral dynamic ranges in control animals. Analyses of threshold tuning curves indicate that the frequency tuning of units in the inferior colliculus of neonatally ablated animals does not differ significantly from the tuning of units in control animals in response to either ipsilateral or contralateral stimulation. These data reveal that in normal gerbils responses of single units in the inferior colliculus to stimulation of the ipsilateral ear result in part from interactions during postnatal development between pathways that convey information from the contralateral ear. The results are discussed in terms of the known anatomic consequences of a neonatal cochlear ablation and the competition for available synaptic space in the development of the retinotectal system.

Acoustic Stimulation↗