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D Jiang

Publications and source records attributed to D Jiang.

At least 19 recordsLinked to original sources

Convergent input from brainstem coincidence detectors onto delay-sensitive neurons in the inferior colliculus.

Responses of low-frequency neurons in the inferior colliculus (IC) of anesthetized guinea pigs were studied with binaural beats to assess their mean best interaural phase (BP) to a range of stimulating frequencies. Phase plots (stimulating frequency vs BP) were produced, from which measures of characteristic delay (CD) and characteristic phase (CP) for each neuron were obtained. The CD provides an estimate of the difference in travel time from each ear to coincidence-detector neurons in the brainstem. The CP indicates the mechanism underpinning the coincidence detector responses. A linear phase plot indicates a single, constant delay between the coincidence-detector inputs from the two ears. In more than half (54 of 90) of the neurons, the phase plot was not linear. We hypothesized that neurons with nonlinear phase plots received convergent input from brainstem coincidence detectors with different CDs. Presentation of a second tone with a fixed, unfavorable delay suppressed the response of one input, linearizing the phase plot and revealing other inputs to be relatively simple coincidence detectors. For some neurons with highly complex phase plots, the suppressor tone altered BP values, but did not resolve the nature of the inputs. For neurons with linear phase plots, the suppressor tone either completely abolished their responses or reduced their discharge rate with no change in BP. By selectively suppressing inputs with a second tone, we are able to reveal the nature of underlying binaural inputs to IC neurons, confirming the hypothesis that the complex phase plots of many IC neurons are a result of convergence from simple brainstem coincidence detectors.

Acoustic Stimulation

Embryonic entorhinal transplants partially ameliorate the deficits in spatial memory in adult rats with entorhinal cortex lesions.

Our previous studies have demonstrated that axons from grafts of embryonic entorhinal cortex (EC) can reinnervate the deafferented zones in the hippocampus and form synaptic connections with the host dentate gyrus in adult mice and rats deprived of their own entorhinal inputs. Here, we have examined the ability of the EC grafts to ameliorate deficits in spatial memory. Three months after transplantation, the grafted rats and control animals were subjected to Morris water maze testing followed by histological examination. According to the exact position of grafts in the host brain, the rats with lesion and EC transplants were divided into two groups, one with EC grafts contacting both the hippocampus and overlying neocortex (n=7, EC1) and another with EC grafts confined within the hippocampus (n=6, EC2). While EC2 rats were still as impaired as those with lesion and transplants of non-entorhinal cortex (n=10, NEC) or with lesions only (n=7, LES), the EC1 rats performed better than the LES group. In a spatial memory trial, the EC1 group made more crossings over platform site and showed more focused search behavior than EC2, LES, NEC groups. The data suggest that EC grafts could partially ameliorate the deficit in spatial learning behavior in the EC-lesioned adult rats. The requirement for the graft to contact both the neocortex and the hippocampus suggests that the functional effects may be exerted by the formation of new neocortical-EC graft-hippocampal circuits.

Animals

Expression of TGFalpha autocrine activity in human colon carcinoma CBS cells is autoregulated and independent of exogenous epidermal growth factor.

Autocrine transforming growth factor alpha (TGFalpha) activity and control mechanisms for its expression were examined in a representative clonal isolate (CBS4) of a well-differentiated human colon carcinoma cell line designated CBS. CBS4 cells expressed TGFalpha and its receptor, epidermal growth factor receptor (EGFr). Blockade of EGFr and TGFalpha by neutralizing antibodies inhibited clonal growth and the initiation of DNA synthesis from quiescence in CBS4 cells. Therefore, TGFalpha is an autocrine growth factor for CBS4 cells. Several studies have indicated that activation of the EGFr by exogenous EGF stimulates TGFalpha expression. However, in CBS4 cells EGF did not induce TGFalpha mRNA expression, indicating that EGF does not affect TGFalpha transcription in these cells. Exogenous treatment of exponentially growing cells with either EGF or EGFr blocking antibody enhanced release of TGFalpha protein into the conditioned medium. This indicated that the release of TGFalpha into the conditioned medium by exogenous EGF was at least partially due to the displacement of TGFalpha from the TGFalpha/EGFr complexes. Similarly to exponentially growing cells, the EGFr blocking antibody and EGF also enhanced TGFalpha release into the medium of CBS4 cells after release from quiescence. These results indicated that exogenous EGF had little if any effect on TGFalpha expression in these cells and suggested that TGFalpha expression might be under endogenous TGFalpha control. Blockade of the autocrine TGFalpha loop by TGFalpha neutralizing antibody suppressed TGFalpha mRNA both in exponentially growing and quiescent cells, demonstrating that autocrine TGFalpha is autoregulatory in this system.

Antibodies

Characterization of Escherichia coli endonuclease VIII.

Escherichia coli endonuclease VIII (endo VIII) was identified as an enzyme that, like endonuclease III (endo III), removes radiolysis products of thymine including thymine glycol, dihydrothymine, beta-ureidoisobutyric acid, and urea from double-stranded plasmid or phage DNA and cleaves the DNA strand at abasic (AP) sites (Melamede, R. J., Hatahet, Z., Kow, Y. W., Ide., H., and Wallace, S. S. (1994) Biochemistry 33, 1255-1264). Using apparently homogeneous endo VIII protein, we now show that endo VIII removes from double-stranded oligodeoxyribonucleotides the stable oxidative products of cytosine, 5-hydroxycytosine and 5-hydroxyuracil. Endo VIII cleaved the damage-containing DNA strand by beta,delta-elimination as does formamidopyrimidine DNA glycosylase (Fpg). Like Fpg, endo VIII also excised the 5'-terminal deoxyribose phosphate from an endonuclease IV (endo IV) pre-incised AP site. Thus, in addition to amino acid sequence homology (Jiang, D., Hatahet, Z., Blaisdell, J., Melamede, R. J., and Wallace, S. S. (1997) J. Bacteriol. 179, 3773-3782), endo VIII shares a number of catalytic properties with Fpg. In addition, endo VIII specifically bound to oligodeoxynucleotides containing a reduced AP site with a stoichiometry of 1:1 for protein to DNA with an apparent equilibrium dissociation constant of 3.9 nM. Like Fpg and endo III, the DNase I footprint was small with contact sites primarily on the damage-containing strand; unlike Fpg and endo III, the DNA binding of endo VIII to DNA was asymmetric, 3' to the reduced AP site.

DNA

Detectability index measures of binaural masking level difference across populations of inferior colliculus neurons.

In everyday life we continually need to detect signals against a background of interfering noise (the "cocktail party effect"): a task that is much easier to accomplish using two ears. The binaural masking level difference (BMLD) measures the ability of listeners to use a difference in binaural attributes to segregate sound sources and thus improve their discriminability against interfering noises. By computing the detectability of tones from rate-versus-level functions in the presence of a suprathreshold noise, we previously demonstrated that individual low-frequency delay-sensitive neurons in the inferior colliculus are able to show BMLDs. Here we consider the responses of a population of such neurons when the noise level is held constant (as conventionally in psychophysical paradigms). We have sampled the responses of 121 units in the inferior colliculi of five guinea pigs to identical noise and 500 Hz tones at both ears (NoSo) and to identical noise but with the 500 Hz tone at one ear inverted (NoSpi). The result suggests that the neurons subserving detection of So tones in No (identical noise at the two ears) noise are those neurons with best frequencies (BFs) close to 500 Hz that respond to So tones with an increase in their discharge rate from that attributable to the noise. The detection of the inverted (Spi) signal is also attributable to neurons with BFs close to 500 Hz. However, among these neurons, the presence of the Spi tone was indicated by an increased discharge rate in some neurons and by a decreased discharge rate in others.

Animals

Innate control of the early course of infection in mice inoculated with Trypanosoma musculi.

Infections of mice with Trypanosoma musculi result in marked suppression of acquired humoral immunity but rapid activation of splenic NK cell cytotoxicity. We show that both NK cells and activated peritoneal space (PS) macrophages (MP) participate in the innate immune control of T. musculi infections preceding escape of curative antibody production from suppression. Splenic NK cytotoxicity reaches a peak on Days 3-4 of infection and then rapidly declines. Rising cytotoxicity is paralleled by a rising number of NK cells. The decline in cytotoxicity occurs even though the number of splenic NK cells continues to rise. The critical role of NK cells in the control of the early course of T. musculi infection was demonstrated by the effects of either depleting NK cells (antiasialo GM1 treatment) or maintaining them in an activated state (poly(I:C) injections). The importance of MP in controlling the infection was suggested by studies involving proteose peptone elicited MP both in vivo and in culture. The results presented here strongly suggest that innate immunity involving NK cells and MP can control, but not cure, T. musculi infections. Whether this early innate response influences the subsequent acquired, curative response remains to be studied. Detailed analyses of innate immunity in this experimental infection should suggest new approaches to intervention in early pathogenic infections.

Animals

Elevated expression of glutathione peroxidase in PC12 cells results in protection against methamphetamine but not MPTP toxicity.

In vivo administration of either 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or methamphetamine (MA) produces damage to the dopaminergic nervous system which may be due in part to the generation of reactive oxygen species (ROS). The resistance of superoxide dismutase (SOD) over-expressing transgenic mice to the effects of both MPTP and MA suggests the involvement of superoxide in the resulting neurotoxicity of both compounds. Superoxide can be converted by SOD to hydrogen peroxide, which itself can cause cellular degeneration by reacting with free iron to produce highly reactive hydroxyl radicals resulting in damage to proteins, nucleic acids and membrane phospholipids. Hydrogen peroxide has also been reported to be produced via inhibition of NADH dehydrogenase by MPP + formed during oxidation of MPTP by MAO-B and by dopamine auto-oxidation following MA-induced dopamine release from synaptic vesicles within nerve terminals. To test whether hydrogen peroxide is an important factor in the toxicity of either of these two neurotoxins, we created clonal PC12 lines expressing elevated levels of the hydrogen peroxide-reducing enzyme glutathione peroxidase (GSHPx). Elevation of GSHPx levels in PC12 was found to diminish the rise in ROS levels and lipid peroxidation resulting from MA but not MPTP treatment. Elevated levels of GSHPx also appeared to prevent decreases in transport-mediated dopamine uptake produced via MA administration as well as to attenuate toxin-induced cell loss as measured by either MTT reduction or LDH release. Our data, therefore, suggest that hydrogen peroxide production likely contributes to MA toxicity in dopaminergic neurons.

Animals

Escherichia coli endonuclease VIII: cloning, sequencing, and overexpression of the nei structural gene and characterization of nei and nei nth mutants.

Escherichia coli possesses two DNA glycosylase/apurinic lyase activities with overlapping substrate specificities, endonuclease III and endonuclease VIII, that recognize and remove oxidized pyrimidines from DNA. Endonuclease III is encoded by the nth gene. Endonuclease VIII has now been purified to apparent homogeneity, and the gene, nei, has been cloned by using reverse genetics. The gene nei is located at 16 min on the E. coli chromosome and encodes a 263-amino-acid protein which shows significant homology in the N-terminal and C-terminal regions to five bacterial Fpg proteins. A nei partial deletion replacement mutant was constructed, and deletion of nei was confirmed by genomic PCR, activity analysis, and Western blot analysis. nth nei double mutants were hypersensitive to ionizing radiation and hydrogen peroxide but not as sensitive as mutants devoid of base excision repair (xth nfo). Single nth mutants exhibited wild-type sensitivity to X rays, while nei mutants were consistently slightly more sensitive than the wild type. Double mutants lacking both endonucleases III and VIII exhibited a strong spontaneous mutator phenotype (about 20-fold) as determined by a rifampin forward mutation assay. In contrast to nth mutants, which showed a weak mutator phenotype, nei single mutants behaved as the wild type.

Amino Acid Sequence

Simian virus 40 T antigen can regulate p53-mediated transcription independent of binding p53.

A simian virus 40 (SV40) T-antigen mutant containing only the N-terminal 136 amino acids, able to bind to Rb and p300 but not p53, partially inhibited p53-mediated transcription without affecting the ability of p53 to bind DNA. These results suggest that SV40 T antigen can regulate p53-mediated transcription either directly through protein-protein association or indirectly through interaction with factors which may function to confer p53-mediated transcription.

Animals

Responses of neurons in the inferior colliculus to binaural masking level difference stimuli measured by rate-versus-level functions.

The psychophysical detection threshold of a low-frequency tone masked by broadband noise is reduced by < or = 15 dB by inversion of the tone in one ear (called the binaural masking level difference: BMLD). The contribution of 120 low-frequency neurons (best frequencies 168-2,090 Hz) in the inferior colliculus (ICC) of the guinea pig to binaural unmasking of 500-Hz tones masked by broadband noise was examined. We measured rate-level functions of the responses to identical signals (So) and noise (No) at the two ears (NoSo) and to identical noise but with the signal inverted at one ear (NoS pi): the noise was 7-15 dB suprathreshold. The masked threshold was estimated by the standard separation, "D". The neural BMLD was estimated as the difference between the masked thresholds for NoSo and NoS pi. The presence of So and S pi tones was indicated by discharge rate increases in 55.3% of neurons. In 36.4% of neurons, the presence of So tones was indicated by an increase in discharge rate and S pi tones by a decrease. In 6.8% of neurons, both So and S pi tones caused a decrease in discharge rate. In only 1.5% of neurons was So indicated by a decrease and S pi by an increase in discharge rate. Responses to the binaural configurations were consistent with the neuron's interaural delay sensitivities; 34.4% of neurons showing increases in discharge rate to both So and S pi tones gave positive BMLDs > or = 3 dB (S pi tones were detected at lower levels than So), whereas 37.3% gave negative BMLDs > or = 3 dB. For neurons in which So signals caused an increase in the discharge rate and S pi a decrease, 72.7% gave positive BMLDs > or = 3 dB and only 4.5% gave negative BMLDs > or = 3 dB. The results suggest that the responses of single ICC neurons are consistent with the psychophysical BMLDs for NoSo versus NoS pi at 500 Hz, and with current binaural interaction models based on coincidence detection. The neurons likely to contribute to the psychophysical BMLD are those with BFs near 500 Hz, but detection of So and S pi tones may depend on different populations of neurons.

Animals

[A fast iterative algorithm for adaptive histogram equalization].

In this paper, we propose an iterative algorthm called FAHE., which is based on the relativity between the current local histogram and the one before the sliding window moving. Comparing with the basic AHE, the computing time of FAHE is decreased from 5 hours to 4 minutes on a 486dx/33 compatible computer, when using a 65 x 65 sliding window for a 512 x 512 with 8 bits gray-level range.

Algorithms

p53 prevents maturation to the CD4+CD8+ stage of thymocyte differentiation in the absence of T cell receptor rearrangement.

Rearrangement of the immunoglobulin (Ig) and T cell receptor (TCR) gene loci allows for the generation of B and T lymphocytes with antigen-specific receptors. Complete rearrangement and expression of the TCR-beta chain enables immature thymocytes to differentiate from the CD4-CD8- to the CD4+CD8+ stage mice in which rearrangement is impaired, such as severe combined immunodeficient (SCID) mice or recombinase activating gene-deficient (RAG-/-) mice, lack mature B and T lymphocytes. Thymocytes from these mice are arrested at the CD4-CD8- stage of T cell development. We previously observed that thymocytes from RAG-2-/- mice exposed to gamma radiation differentiate from CD4-CD8- into CD4+CD8+ without TCR-beta chain rearrangement. We now report that irradiated RAG-2-/- thymocytes undergo direct somatic mutations at the p53 gene locus, and that p53 inactivation is associated with maturation of RAG2-/- thymocytes to the CD4+CD8+ stage. Generation of RAG2-/- and p53-/- double-deficient mice revealed that, in the absence of TCR-beta chain rearrangement, loss of p53 function is sufficient for CD4-CD8- thymocytes to differentiate into the CD4+CD8+ stage of T cell development. Our data provide evidence for a novel p53 mediated checkpoint in early thymocyte development that regulates the transition of CD4-CD8- into CD4+CD8+ thymocytes.

Animals

Binaural masking level differences in the inferior colliculus of the guinea pig.

The binaural masking level difference (BMLD) is a striking and well-documented psychophysical effect which relates to the ability to use the phase of low-frequency sounds to dissociate them from masking noise. When identical tones and noise are presented to both ears, detectability is improved by up to 15 dB simply by inverting the phase of either the tone or noise in one ear. Measurements of BMLDs were made in single delay-sensitive neurones in the inferior colliculus of the guinea pig. These have confirmed and extended an earlier report [D. M. Caird, A. R. Palmer, and A. Rees, Hear. Res. 57, 91-106 (1991)] by demonstrating that when signals are optimized for the frequency, level, and interaural delay sensitivities of each neurone, BMLDs can be measured which are in a direction, and of a magnitude, consistent with appropriate psychophysical observations in human subjects. In addition, BMLDs were found to be consistent with the delay sensitivities of the neurones to the signal and masker, the major determinant of the masked threshold for optimized signals being the activity evoked in the neurone by the masking noise. Within-channel signal-to-noise (S/N) ratios at masked threshold for single neurones varied from +20 to -7 dB, depending on the binaural configuration and the units' delay sensitivities. In single neurones, the size of the BMLD for optimized signals increased with the level of the noise. The BMLD increased by 5 dB over a 40-dB range of noise, consistent with psychophysical observations. This came about because as noise level increased, masked threshold for optimized tones increased more slowly in Npi noise than in N0 noise. For all binaural comparisons, both positive (pi signals more detectable, as in the psychophysics) and negative BMLDs were observed, often in the same neurone, a result entirely consistent with the sensitivity to the interaural delay of the noise and tone signals. For 500-Hz signals in zero and pi phase masked by identical noise the majority of BMLDs determined with the PEST procedure was negative, a result which is taken to indicate that increases in spike rate may not be an appropriate cue for masked threshold under these conditions.

Animals

Frequency extent of two-tone facilitation in onset units in the ventral cochlear nucleus.

1. The frequency threshold curves (FTCs) of 91 single units in the cochlear nucleus of the anesthetized guinea pig were measured using a conventional single-tone paradigm and a two-tone paradigm designed to elucidate the frequency extent of two-tone facilitation in onset units (On). Units were classified according to existing classification schemes into primary-like (n = 3), chopper (n = 23), and three onset groups: OnI (n = 12), OnC (n = 29), and OnL (n = 24). Histological reconstructions show onset units to be widely distributed within the ventral cochlear nucleus in a manner generally consistent with its tonotopic organization. 2. The FTCs of onset units differed in their minimum thresholds, the steepness of their high- and low-frequency cutoffs, and their sharpness of tuning as quantified by the quality factor at 10 dB (Q10dB) above best frequency (BF) threshold values. There was considerable overlap in the sharpness of tuning between onset units and auditory nerve fibers, as indicated by the distribution of Q10dB values in the octave around 10 kHz: onset units had Q10dB values of 3.56 +/- 1.38 (SD), compared with 6.3 +/- 2.48 for auditory nerve fibers. The tuning of chopper units was similar to that of auditory nerve fibers (5.52 +/- 1.46). 3. Seventy-five percent of onset units showed some degree of facilitation (a threshold reduction) when their FTCs were measured in the presence of BF tones 4 dB below BF threshold. The frequency extent of such facilitation was variable, with a maximum of 6 octaves around the BF. In extreme cases facilitation could be measured when the BF tone was as low as 30 dB below BF threshold. 4. In 17% of onset units, suppressive effects were evident, as shown by noncontiguous frequency regions of facilitation. These suppressive effects might be a reflection either of suppression in the auditory nerve input or of a direct inhibitory input to the onset units. The strength of this effect suggests that inhibition is a likely explanation, consistent with the finding in previous morphological studies of profuse synapses with pleomorphic vesicles on multipolar cells. 5. FTCs of chopper and primary-like units measured in the presence of BF tones showed little facilitation. The facilitation that was observed in chopper units was confined to a narrow region around BF and disappeared when the facilitatory tone was lowered to 4 dB below BF threshold. 6. These data support the hypothesis that onset units, but not chopper or primary-like units, receive excitatory inputs from auditory nerve fibers with a wide range of BFs. However, the frequency range of facilitation and the magnitude of the threshold facilitation varied from unit to unit, suggesting that the off-BF inputs from auditory nerve fibers are not evenly distributed or equally effective in all units.

Acoustic Stimulation

Responses of ventral cochlear nucleus onset and chopper units as a function of signal bandwidth.

1. The responses of units in the ventral cochlear nucleus in anesthetized guinea pigs have been measured to best-frequency tones, noise bands geometrically centered around the unit best frequency, and noise bands asymmetrically positioned around the best frequency. 2. Each unit isolated was characterized using peristimulus time histograms (PSTHs) to best-frequency tones at 20 and 50 dB suprathreshold, frequency-intensity response areas and rate-versus-level functions in response to best-frequency tones and wideband noise. The data reported here are derived from full analyses of 5 chopper units and 17 onset units. The onsets were divided into onset-I (OnI), onset-L (OnL), and onset-C (OnC) by the criteria described by Winter and Palmer: the PSTHs of OnI units show only an onset response, OnL units respond with a single spike at onset followed by a low level of sustained activity, and OnC units have PSTHs with one to four onset peaks and low levels of sustained discharge. 3. In response to geometrically centered noise bands of constant spectral density, the discharge of chopper units and one OnI unit increased over a relatively narrow range of bandwidths, corresponding to the equivalent rectangular bandwidth calculated from their response area, and then became constant. In contrast, OnL and OnC units showed increases in discharge rate with noise bandwidth over very wide ranges of bandwidth. The growth of the discharge rate with noise bandwidth was approximately linear on double logarithmic axes and therefore could be described by a power function with an exponent of 0.37. This relation held even for noise levels near threshold. 4. When noise bands with constant spectral density (at the input to the earphone) were presented with one edge fixed at the unit's best frequency, the discharge rate of most chopper units and the one OnI unit increased over a narrow range of bandwidths and then became constant. This pattern was observed irrespective of whether the second edge of the noise was progressively increased above, or decreased below, the best frequency. For two of the chopper units, in which lateral inhibitory sidebands could be demonstrated, increasing the noise bandwidth led first to increases and then to decreases in the discharge rate as the noise energy impinged upon the sideband. The chopper units act like energy detectors with a filter corresponding to their single tone response area, but, for some units, with the addition of inhibitory sidebands. 5. For the OnL and OnC units, increasing the noise bandwidth above or below best frequency caused progressive increases in the discharge rate over wide ranges of bandwidth. These increases occurred even for low noise spectral densities. The growth in discharge rate for these onset units was well fitted at all spectral density levels by power functions: one above best frequency and one below. At levels of the noise 40 dB above the unit threshold, the point at which the discharge rate reached 90% of its maximum was, on average, about 2 octaves below best frequency and 1 octave above. For some onset units, changes in the discharge rate were seen as the noise bandwidth was varied over about 14 kHz, which is about one-third of the total frequency hearing range of the guinea pig. 6. The data for onset units is consistent with the hypothesis that onset units in the ventral cochlear nucleus achieve their precision in the temporal domain by integration of the inputs from auditory nerve fibers with a wide range of best frequencies. The range of frequency over which onset units integrate frequency matches that of the inhibitory input to dorsal cochlear nucleus neurons, suggesting a possible role as an inhibitory interneuron.

Acoustic Stimulation

Interaural delay sensitivity and the classification of low best-frequency binaural responses in the inferior colliculus of the guinea pig.

Monaural and binaural response properties of single units in the inferior colliculus (IC) of the guinea pig were investigated. Neurones were classified according to the effect of monaural stimulation of either ear alone and the effect of binaural stimulation. The majority (309/334) of IC units were excited (E) by stimulation of the contralateral ear, of which 41% (127/309) were also excited by monaural ipsilateral stimulation (EE), and the remainder (182/309) were unresponsive to monaural ipsilateral stimulation (EO). For units with best frequencies (BF) up to 3 kHz, similar proportions of EE and EO units were observed. Above 3 kHz, however, significantly more EO than EE units were observed. Units were also classified as either facilitated (F), suppressed (S), or unaffected (O) by binaural stimulation. More EO than EE units were suppressed or unaffected by binaural stimulation, and more EE than EO units were facilitated. There were more EO/S units above 1.5 kHz than below. Binaural beats were used to examine the interaural delay sensitivity of low-BF (BF < 1.5 kHz) units. The distributions of preferred interaural phases and, by extension, interaural delays, resembled those seen in other species, and those obtained using static interaural delays in the IC of the guinea pig. Units with best phase (BP) angles closer to zero generally showed binaural facilitation, whilst those with larger BPs generally showed binaural suppression. The classification of units based upon binaural stimulation with BF tones was consistent with their interaural-delay sensitivity. Characteristic delays (CD) were examined for 96 low-BF units. A clear relationship between BF and CD was observed. CDs of units with very low BFs (< 200 Hz) were long and positive, becoming progressively shorter as BF increased until, for units with BFs between 400 and 800 Hz, the majority of CDs were negative. Above 800 Hz, both positive and negative CDs were observed. A relationship between CD and characteristic phase (CP) was also observed, with CPs increasing in value as CDs became more negative. These results demonstrate that binaural processing in the guinea pig at low frequencies is similar to that reported in all other species studied. However, the dependence of CD on BF would suggest that the delay line system that sets up the interaural-delay sensitivity in the lower brainstem varies across frequency as well as within each frequency band.

Acoustic Stimulation