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Biomedical subjects

K A Davis

Publications and source records attributed to K A Davis.

At least 19 recordsLinked to original sources
PubMed1999

Early and late acute respiratory distress syndrome: two distinct clinical entities.

BACKGROUND: Despite numerous advances in surgical critical care and ventilatory management, mortality rates for acute respiratory distress syndrome (ARDS) have remained relatively constant. Pressure-limited and non-pressure-limited ventilatory techniques have been advocated with disparate results. We hypothesized that there are two forms of ARDS, which may account for the conflicting clinical reports. METHODS: Patients with posttraumatic ARDS were identified and reviewed. ARDS was defined as PaO2/FiO2 ratio less than 200 with diffuse bilateral infiltrates on chest radiograph and no congestive heart failure. Patients were analyzed relative to injury mechanism, transfusions, fluid balance, presence of pneumonia (defined as > or =10(5) colony-forming units/mL in bronchoalveolar lavage effluent), and outcome. All were managed with a non-pressure-limited strategy. RESULTS: During a 5.5-year period, 178 patients with posttraumatic ARDS were identified. Mean Injury Severity Score and age were 29 and 40 years, respectively. Patients were stratified by time of ARDS diagnosis. Eighty-two patients (46%) had early ARDS (within 48 hours after admission), and 96 patients (54%) had late ARDS (>48 hours between admission and diagnosis). There were no differences in Injury Severity Score, but the late group was significantly older. The early ARDS group was characterized by profound hemorrhagic shock and had significant differences from the late group in incidence of penetrating injury (30 vs. 10%; p<0.001), admission base deficit (-7.7 vs. -4.2 mEq/L; p<0.001), 48-hour transfusions (19.7 vs. 9.4; p<0.0001), initial 5-day fluid balance (19.9 vs. 10.1 L; p<0.0001), and initial PaO2/FiO2 (121 vs. 141; p<0.007). Pneumonia before ARDS was significantly associated with late ARDS (38 vs. 9%; p<0.001). ARDS-related mortality was primarily caused by hemorrhagic shock in the early group and progressive multiple organ failure in the late group. CONCLUSION: There are two distinct forms of posttraumatic ARDS. Early ARDS is characterized by hemorrhagic shock with capillary leak. Late ARDS frequently follows pneumonia and is associated with multiple system injury. Further studies should differentiate between these two distinct syndromes.

Adolescent↗
PubMed1999

Prostanoids: early mediators in the secondary injury that develops after unilateral pulmonary contusion.

BACKGROUND: We have previously shown a sequence of events after unilateral pulmonary contusion that suggests the release of blood-borne prostanoid mediators and that culminates in refractory bilateral pulmonary failure. PURPOSE: To determine the role of platelet-derived thromboxane and endothelial-derived prostacyclin in the primary and secondary injury after unilateral blunt chest trauma, and to determine whether pretreatment with the cyclooxygenase inhibitor indomethacin alters the progression of secondary injury. METHODS: Anesthetized, ventilated (FIO2 = 0.50) pigs received a unilateral, blunt injury to the right thorax (n = 20) or sham injury (n = 5) and were monitored for 24 hours. Either indomethacin (5 mg/kg i.v.; n = 10) or its saline vehicle (n = 10) were administered 15 minutes before injury. Serial bronchoalveolar lavages of each lung were analyzed for protein and neutrophil (polymorphonuclear neutrophil (PMN)) content. RESULTS: Contusion caused profound hypoxemia; PaO2 partially recovered within 1 hour of injury to 50% of baseline. Thereafter, worsening hypoxemia required positive end-expiratory pressure. With indomethacin compared with vehicle, PaO2 was higher at any given level of positive end-expiratory pressure (p < 0.05). There was an early increase in serial bronchoalveolar lavage protein on the injured side (peak at 2 hours), with a delayed pulmonary capillary leak on the contralateral side (peak at 6 hours), which correlated with increasing PMN infiltration; this was reduced by 40 to 60% with indomethacin (p < 0.05). Thromboxane peaked within 1 hour after contusion at 800% baseline, then fell off rapidly. This peak preceded the maximal increase in permeability and was completely blocked by indomethacin. Prostacyclin slowly rose to 300% baseline by 3 hours and remained elevated; this change was blocked by indomethacin for 18 hours. CONCLUSIONS: Contusion of the right thorax induced a delayed pulmonary capillary leak in the left lung, which reflects a progressive secondary inflammatory response. Elevations in thromboxane and prostacyclin preceded progressive bilateral PMN infiltration. Indomethacin blocked thromboxane and prostacyclin and attenuated, but did not prevent, the progression to pulmonary failure. Overall, these data suggest that prostanoids are released soon after unilateral contusion and initiate an inflammatory response in both lungs that is sustained by PMN infiltration.

6-Ketoprostaglandin F1 alpha↗
PubMed1999

Single-unit responses in the inferior colliculus of decerebrate cats. I. Classification based on frequency response maps.

This study proposes a classification system for neurons in the central nucleus of the inferior colliculus (ICC) that is based on excitation and inhibition patterns of single-unit responses in decerebrate cats. The decerebrate preparation allowed extensive characterization of physiological response types without the confounding effects of anesthesia. The tone-driven discharge rates of individual units were measured across a range of frequencies and levels to map excitatory and inhibitory response areas for contralateral monaural stimulation. The resulting frequency response maps can be grouped into the following three populations: type V maps exhibit a wide V-shaped excitatory area and no inhibition; type I maps show a more restricted I-shaped region of excitation that is flanked by inhibition at lower and higher frequencies; and type O maps display an O-shaped island of excitation at low stimulus levels that is bounded by inhibition at higher levels. Units that produce a type V map typically have a low best frequency (BF: the most sensitive frequency), a low rate of spontaneous activity, and monotonic rate-level functions for both BF tones and broadband noise. Type I and type O units have BFs that span the cat's range of audible frequencies and high rates of spontaneous activity. Like type V units, type I units are excited by BF tones and noise at all levels, but their rate-level functions may become nonmonotonic at high levels. Type O units are inhibited by BF tones and noise at high levels. The existence of distinct response types is consistent with a conceptual model in which the unit types receive dominant inputs from different sources and shows that these functionally segregated pathways are specialized to play complementary roles in the processing of auditory information.

Acoustic Stimulation↗
PubMed1999

Single-unit responses in the inferior colliculus of decerebrate cats. II. Sensitivity to interaural level differences.

Single units in the central nucleus of the inferior colliculus (ICC) of unanesthetized decerebrate cats can be grouped into three distinct types (V, I, and O) according to the patterns of excitation and inhibition revealed in contralateral frequency response maps. This study extends the description of these response types by assessing their ipsilateral and binaural response map properties. Here the nature of ipsilateral inputs is evaluated directly using frequency response maps and compared with results obtained from methods that rely on sensitivity to interaural level differences (ILDs). In general, there is a one-to-one correspondence between observed ipsilateral input characteristics and those inferred from ILD manipulations. Type V units receive ipsilateral excitation and show binaural facilitation (EE properties); type I and type O units receive ipsilateral inhibition and show binaural excitatory/inhibitory (EI) interactions. Analyses of binaural frequency response maps show that these ILD effects extend over the entire receptive field of ICC units. Thus the range of frequencies that elicits excitation from type V units is expanded with increasing levels of ipsilateral stimulation, whereas the excitatory bandwidth of type I and O units decreases under the same binaural conditions. For the majority of ICC units, application of bicuculline, an antagonist for GABAA-mediated inhibition, does not alter the basic effects of binaural stimulation; rather, it primarily increases spontaneous and maximum discharge rates. These results support our previous interpretations of the putative dominant inputs to ICC response types and have important implications for midbrain processing of competing free-field sounds that reach the listener with different directional signatures.

Acoustic Stimulation↗
PubMed1998

Normal human CD4+ memory T cells display broad heterogeneity in their activation threshold for cytokine synthesis.

CD4+ memory T cells coordinate immune responses against viruses and other pathogens via the Ag-induced secretion of potent effector cytokines. The efficacy of these responses depends on both the overall number of pathogen-specific memory T cells and the particular array of cytokines that these cells are programmed to secrete. Here, we provide evidence that heterogeneity in Ag triggering thresholds constitutes an additional critical determinant of memory T cell function. Using a novel assay that allows single-cell detection of Ag-specific T cell cytokine production, we demonstrate that CMV-specific CD4+ memory cells from human peripheral blood display pronounced differences in their costimulatory requirements for Ag-induced triggering of IFN-gamma and IL-2 secretion, ranging from cells that trigger with little costimulation (e.g., resting APC alone) to cells requiring potent costimulation through multiple pathways (resting APC plus multiple costimulatory mAbs, or activated APC). These differences in costimulatory requirements are independent of clonal differences in TCR signaling intensity, consistent with an intrinsic activation-threshold heterogeneity that is "downstream" from the TCR. Thus, "effective" frequencies of Ag-specific CD4+ memory T cells appear to depend on the activation status of available APC, a dependence that would allow the immune system to rapidly adjust the number of functional Ag-specific memory T cells in a particular effector site according to local conditions.

Antibodies, Monoclonal↗
PubMed1998

Determination of CD4 antigen density on cells: role of antibody valency, avidity, clones, and conjugation.

The number of R-phycoerythrin (R-PE)-conjugated antibodies bound to a cell can be quantitated on a flow cytometer by using beads with known numbers of attached R-PE molecules (QuantiBRITE PE). Using these reference beads, we have observed that a number of factors affect the accuracy of the quantitation and conclusions about epitope density. These factors include valence of antibody binding, the use of antibody fragments (Fab's) versus intact monoclonal antibodies (mAb's), fixation, the purity of the conjugate (i.e., percentage of 1:1 ratios), dissociation rate, the use of washed versus unwashed preparations, and the location of epitope on target antigen. We used CD4 on T cells as a model to explore these challenges in detail. We conclude that CD4+ T cells bind approximately 49,000 CD4 (Leu 3a) antibody molecules, that this binding is bivalent, and therefore that there are approximately 98,000 CD4 antigen molecules on the surface of these cells.

Antibodies, Monoclonal↗
PubMed1998

Quantitation of CD38 expression using QuantiBRITE beads.

The QuantiBRITE bead method was compared with the CD4 biological calibration method for quantitation of CD38 expression on CD8+ T-lymphocytes of Multicenter AIDS Cohort Study participants. Results were expressed as CD38 antibodies bound per cell (ABCs) and were the same with the two methods provided two conditions were met. These were the use of repurified (> 95% of the monoclonal antibodies [mAbs] have 1 phycoerythrin [PE] molecule per mAb) CD38-PE for both methods and use of repurified CD4-PE to calculate the relative fluorescence intensity multiplier for the CD4 biological calibration method. Our results indicate that the prognostic significance of CD38 values obtained using the QuantiBRITE method can be interpreted using previously published reports (Liu et al.: J Acquir Immune Defic Syndr Hum Retrovirol 16:83-92, 1997 and 18:332-340, 1998). Sample preparation using NH4Cl and FACS lysing solution gave similar results for CD38 relative fluorescence intensity. Dilution into either phosphate-buffered saline with 2% fetal calf serum and 0.1% sodium azide or fixation in 1% paraformaldehyde for 1 or 24 h also gave similar results. In experiments using Raji cells, which express high levels of CD38, the valence of binding of the intact Leu 17 antibody was approximately 68% bivalent and approximately 32% monovalent. This emphasizes the complexity of determining antigen density from ABCs. We conclude that repurified PE conjugates of CD38, which can be consistently made, together with QuantiBRITE PE beads, provide a convenient and reliable method for quantitation of CD38 expression as ABCs.

ADP-ribosyl Cyclase↗
PubMed1998

Staining of cell surface human CD4 with 2'-F-pyrimidine-containing RNA aptamers for flow cytometry.

We have used recombinant human CD4 presented on beads as an affinity matrix to screen a 2'-F-pyrimidine-containing RNA library with a complexity of approximately 10(14) molecules. Affinity-selected aptamers bind recombinant CD4 with low nanomolar equilibrium dissociation constants. These high-affinity aptamers conjugated to different fluorophores such as fluorescein and phycoerythrin were used to stain cells, expressing human CD4 on cell surface, for analysis by flow cytometry. Aptamers, conjugated to fluorophores, stained mouse T cells that express human CD4 on the surface, but not the control mouse T cells lacking human CD4. The control cells, however, do express mouse CD4 whose extracellular domain has 55% sequence identity to the human form. These human CD4-specific aptamers selectively stained CD4(+) T cells in a preparation of human peripheral blood mononuclear cells. These results and others suggest that aptamers are emerging as a versatile class of molecules that can be used for various diagnostic applications performed under different formats or platforms.

Amino Acid Sequence↗
PubMed1998

Acetylcholine metabolism in the inflamed rat intestine.

Acetylcholine (ACh) is a major neurotransmitter in the enteric nervous system. Since increasing evidence suggests that inflammation alters neural regulation of intestinal function, we examined the synthesis and breakdown of ACh in smooth muscle/myenteric plexus (SM/MP) preparations from the jejunum of the rat during inflammation caused by infection with the nematode parasite Trichinella spiralis. Both total and neuron-specific uptake of the ACh precursor [3H]choline into SM/MP preparations was increased by over twofold on Day 6 postinfection. Further, a radiochemical assay of choline acetyltransferase activity showed significant increase by Day 1, with peak values reached by Day 3 and maintained without reversal thereafter. Despite the enhancement of these steps, measurement of the conversion of [3H]choline into [3H]ACh in SM/MP preparations in vitro showed a nearly fourfold decrease by Day 6, implying a large decrease in ACh production in the inflamed jejunum. Examination of acetylcholinesterase in the rat jejunum showed decreased histochemical staining intensity in the muscle wall, and quantitative evaluation showed significantly decreased (>50%) acetylcholinesterase activity in SM/MP preparations. These results show that cholinergic innervation of the intestine can undergo rapid and long-lasting alterations during inflammation. Upregulation of major steps in the synthetic pathway for ACh was not matched by increased ACh production, suggesting that defects in ACh packaging, storage, and granule exocytosis may also be present.

Acetylcholine↗
PubMed1998

Prospective study of blunt aortic injury: helical CT is diagnostic and antihypertensive therapy reduces rupture.

OBJECTIVE: There were two aims of this study. The first was to evaluate the application of helical computed tomography of the thorax (HCTT) for the diagnosis of blunt aortic injury (BAI). The second was to evaluate the efficacy of beta-blockers with or without nitroprusside in preventing aortic rupture. SUMMARY BACKGROUND DATA: Aortography has been the standard for diagnosing BAI for the past 4 decades. Conventional chest CT has not proven to be of significant value. Helical CT scanning is faster and has higher resolution than conventional CT. Retrospective studies have suggested the efficacy of antihypertensives in preventing aortic rupture. METHODS: A prospective study comparing HCTT to aortography in the diagnosis of BAI was performed. A protocol of beta-blockers with or without nitroprusside was also examined for efficacy in preventing rupture before aortic repair and in allowing delayed repair in patients with significant associated injuries. RESULTS: Over a period of 4 years, 494 patients were studied. BAI was diagnosed in 71 patients. Sensitivity was 100% for HCTT versus 92% for aortography. Specificity was 83% for HCTT versus 99% for aortography. Accuracy was 86% for HCTT versus 97% for aortography. Positive predictive value was 50% for HCTT versus 97% for aortography. Negative predictive value was 100% for HCTT versus 97% for aortography. No patient had spontaneous rupture in this study. CONCLUSIONS: HCTT is sensitive for diagnosing intimal injuries and pseudoaneurysms. Patients without direct HCTT evidence of BAI require no further evaluation. Aortography can be reserved for indeterminate HCTT scans. Early diagnosis with HCTT and presumptive treatment with the antihypertensive regimen eliminated in-hospital aortic rupture.

Adrenergic beta-Antagonists↗
PubMed1998

Improved success in nonoperative management of blunt splenic injuries: embolization of splenic artery pseudoaneurysms.

OBJECTIVES: By using abdominal computed tomographic scans in the evaluation of blunt splenic trauma, we previously identified the presence of vascular blush as a predictor of failure, with a failure of nonoperative management of 13% in that series. This finding led to an alteration in our management scheme, which now includes the aggressive identification and embolization of splenic artery pseudoaneurysms. METHODS: The medical records of 524 consecutive patients with blunt splenic injury managed over a 4.5-year period were reviewed for the following information: age, Injury Severity Score (ISS), American Association for the Surgery of Trauma splenic injury grade (SIG), method and outcome of management. RESULTS: Of the patients, 66% were male with a mean age of 32 +/- 16, and mean ISS of 25 +/- 13. A total of 180 patients (34%) were managed with urgent operation on admission (81% splenectomy (SIG 4.0), 19% splenorrhaphy (SIG 2.6)). The remaining 344 patients (66%) were hemodynamically stable and underwent computed tomographic scan and planned nonoperative management. Of these patients, 322 patients (94%) were successfully managed nonoperatively (61% of total splenic injuries). In 26 patients (8%), a contrast blush identified on computed tomographic scan was confirmed as a parenchymal pseudoaneurysm on arteriography. Twenty patients (SIG, 2.8) were successfully embolized. In six patients, technical failure precluded embolization; all required splenectomy (SIG, 4.0). A total of 22 patients (6%) failed nonoperative management, including the six with unsuccessful embolization attempts. Sixteen patients (SIG, 3.0) who had no evidence of pseudoaneurysm were explored for a falling hematocrit, hemodynamic instability, or a worsening follow-up computed tomography: 13 patients had splenectomy, and three patients had splenorrhaphy. CONCLUSIONS: Aggressive surveillance for and embolization of posttraumatic splenic artery pseudoaneurysms improved the rate of successful nonoperative management of blunt splenic trauma to 61%, with a nonoperative failure rate of only 6%. In comparison with our previous work, this reduction in failure of nonoperative management is a significant improvement (p < 0.03).

Adolescent↗
PubMed1997

A flow cytometric immunoassay for beta2-microglobulin in whole blood.

Flow cytometers can discriminate a single particle type in an unwashed whole blood sample. Utilizing this capability. we devised a homogeneous bead-immobilized sandwich immunoassay for soluble beta2M (beta2-microglobulin) in whole blood, utilizing an antibody that discriminates soluble from cellular beta2M. A 4 microm bead was chosen that fluoresces only in a FACScan flow cytometer's FL3 channel. thus allowing triggering on this bead to the exclusion of the many blood cell events. The bead was adsorbed with a capture antibody (clone A7801) which binds only to soluble and not to cellular beta2M. This antibody appears to recognize an epitope on beta2M which interfaces to the heavy chain of cellular Class I MHC molecules. The signal antibody (PE conjugate of clone L376, emitting in the FL2 channel) binds to both soluble and cellular beta2M (present in roughly equal amounts in normal blood). The various parameters required for a flow cytometric immunoassay were optimized. The 4 microm sized bead was adequately large to give a near full scale signal at saturation. The relative amounts of signal antibody and capture beads were balanced to give a low blank, minimal 'hook effect', and reasonable event rate on the flow cytometer. The amount of blood added was selected to give a signal near the bottom of the immunassay range for normals with the higher range available for clinical samples. The assay requires no washing, minimizes blood handling, and has a working range (2.5 decades) that is compatible with the biological range of beta2M concentrations with a single blood dilution.

Animals↗
PubMed1997

P-glycoprotein function involves conformational transitions detectable by differential immunoreactivity.

The MDR1 P-glycoprotein (Pgp), a member of the ATP-binding cassette family of transporters, is a transmembrane ATPase efflux pump for various lipophilic compounds, including many anti-cancer drugs. mAb UIC2, reactive with the extracellular moiety of Pgp, inhibits Pgp-mediated efflux. UIC2 reactivity with Pgp was increased by the addition of several Pgp-transported compounds or ATP-depleting agents, and by mutational inactivation of both nucleotide-binding domains (NBDs) of Pgp. UIC2 binding to Pgp mutated in both NBDs was unaffected in the presence of Pgp transport substrates or in ATP-depleted cells, whereas the reactivities of the wild-type Pgp and Pgps mutated in a single NBD were increased by these treatments to the level of the double mutant. These results indicate the existence of different Pgp conformations associated with different stages of transport-associated ATP hydrolysis and suggest trapping in a transient conformation as a mechanism for antibody-mediated inhibition of Pgp.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Granule cell activation of complex-spiking neurons in dorsal cochlear nucleus.

Dorsal cochlear nucleus (DCN) principal cells receive, in addition to their well known auditory inputs, various nonauditory inputs via a cerebellar-like granule cell circuit located in the superficial layers of the DCN. Activation of this circuit (granule cell axons make excitatory synapses on the principal cells but also contact inhibitory interneurons that project to the principal cells) produces strong inhibition of the principal cells. Here we investigate the role of cartwheel cells, homologs of cerebellar Purkinje cells, in producing this inhibition. The responses of type IV units (one type of principal cells) and of cartwheel cells were recorded to ortho- and antidromic activation of the granule cells (i. e., by stimulation of their inputs from the somatosensory cuneate and spinal trigeminal nuclei and by direct stimulation of their parallel fiber axons). Cartwheel cells were identified on the basis of recording depth and complex action potential shape. A four-pulse facilitation paradigm (four pulses at 50 msec intervals) was used; this stimulus allows separation of the apparently simple inhibitory somatosensory response of type IV units into a three-component (inhibition-excitation-inhibition) response. As expected, cartwheel cells are excited by granule cell activation; the latencies and four-pulse amplitudes of these responses correspond to the properties of the second, long-latency inhibitory component of type IV responses. The source of the first, short-latency inhibitory response is still unknown. Nevertheless, these results show that cartwheel cells convey inhibitory polysensory information to DCN principal cells.

Animals↗
PubMed1997

Affinity modulation of platelet integrin alphaIIbbeta3 by beta3-endonexin, a selective binding partner of the beta3 integrin cytoplasmic tail.

Platelet agonists increase the affinity state of integrin alphaIIbbeta3, a prerequisite for fibrinogen binding and platelet aggregation. This process may be triggered by a regulatory molecule(s) that binds to the integrin cytoplasmic tails, causing a structural change in the receptor. beta3-Endonexin is a novel 111-amino acid protein that binds selectively to the beta3 tail. Since beta3-endonexin is present in platelets, we asked whether it can affect alphaIIbbeta3 function. When beta3-endonexin was fused to green fluorescent protein (GFP) and transfected into CHO cells, it was found in both the cytoplasm and the nucleus and could be detected on Western blots of cell lysates. PAC1, a fibrinogen-mimetic mAb, was used to monitor alphaIIbbeta3 affinity state in transfected cells by flow cytometry. Cells transfected with GFP and alphaIIbbeta3 bound little or no PAC1. However, those transfected with GFP/beta3-endonexin and alphaIIbbeta3 bound PAC1 specifically in an energy-dependent fashion, and they underwent fibrinogen-dependent aggregation. GFP/beta3-endonexin did not affect levels of surface expression of alphaIIbbeta3 nor did it modulate the affinity of an alphaIIbbeta3 mutant that is defective in binding to beta3-endonexin. Affinity modulation of alphaIIbbeta3 by GFP/beta3-endonexin was inhibited by coexpression of either a monomeric beta3 cytoplasmic tail chimera or an activated form of H-Ras. These results demonstrate that beta3-endonexin can modulate the affinity state of alphaIIbbeta3 in a manner that is structurally specific and subject to metabolic regulation. By analogy, the adhesive function of platelets may be regulated by such protein-protein interactions at the level of the cytoplasmic tails of alphaIIbbeta3.

Animals↗
PubMed1997

Modeling inhibition of type II units in the dorsal cochlear nucleus.

Type II units in the dorsal cochlear nucleus (DCN) are characterized by vigorous but nonmonotonic responses to best frequency tones as a function of sound pressure level, and relatively weak responses to noise. A model of DCN neural circuitry was used to explore two hypothetical mechanisms by which neurons may be endowed with type II unit response properties. Both mechanisms assume that type II units receive excitatory input from auditory nerve (AN) fibers and inhibitory input from an unspecified class of cochlear nucleus interneurons that also receive excitatory AN input. The first mechanism, a lateral inhibition (LI) model, supposes that type II units receive inhibitory input from a number of narrowly tuned interneurons whose best frequencies (BFs) flank the BF of the type II unit. Tonal stimuli near BF result in only weak inhibitory input, but broadband stimuli recruit enough lateral inhibitors to greatly weaken the type II unit response. The second mechanism, a wideband inhibition (WBI) model, supposes that type II units receive inhibitory input from interneurons that are broadly tuned so that they respond more vigorously to broadband stimuli than to tones. Physiological and anatomical evidence points to the possible existence of such a class of neurons in the cochlear nucleus. The model extends an earlier computer model of an iso-frequency DCN patch to multiple frequency slices and adds a population of interneurons to provide the inhibition to model type II units (called 12-cells). The results show that both mechanisms accurately simulate responses of type II units to tones and noise. An experimental paradigm for distinguishing the two mechanisms is proposed.

Acoustic Stimulation↗
PubMed1997

Evidence of stimulus-dependent correlated activity in the dorsal cochlear nucleus of decerebrate gerbils.

Cross-correlation analysis of simultaneously recorded spike trains was used to study the internal organization of the dorsal cochlear nucleus (DCN) of unanesthetized decerebrate Mongolian gerbils. The goal was to test the model (adapted from cat) that its principal cells (type III and type IV units) receive three sources of shared auditory input: excitatory input from the auditory nerve; inhibitory input from DCN interneurons (vertical cells; type II and type II-i units) that respond vigorously to tones; and inhibitory input from ventral cochlear nucleus principal cells (D-stellate cells; wideband inhibitors) that conversely respond vigorously to noise. Records of spontaneous and/or driven activities (to long-duration tones and frozen broadband noise) were obtained for 51 pairs consisting of type II, type III, and type IV units; type III units inhibited by low-level noise were subclassified as type III-i units. Pairs were isolated with two electrodes to study the effect of differences in unit best frequencies (BFs) on correlation. All correlated pairs composed of type III and type IV units (17 of 31 pairs) showed central mounds (CMs), indicative of shared input, in their cross-correlograms. These data exhibited two important properties: pairs with similar BFs were more likely to show CMs, and the shape of the CMs was stimulus dependent. That is, CM width typically changed sharply from wide to narrow with increasing level; significantly, transition-level CMs were either a composite of these shapes or not present. The transition to only narrow CMs occurred above the thresholds of type II and type III-i units to tones, but below their thresholds to noise. Cross-correlograms derived from the tone-evoked activities of pairs involving type II units (3 of 6 pairs) showed inhibitory troughs (ITs); unexpectedly, type III-i units were involved in both IT and CM pairs, suggesting that this unit type may reflect recordings from both vertical and principal cells. Overall, the results are interpretable in terms of the model of gerbil DCN that was adapted from cat, suggesting that the model generalizes across species. Compared with cat, however, gerbil principal cell responses (predominantly type III unit properties) are less dominated by inhibition.

Acoustic Stimulation↗