[Devitalization of cholesteatoma on human ossicles by hydrostatic high pressure treatment]. / Devitalisierung von Cholestatomanteilen humaner Ossikel durch hydrostatische Hochdrucktechnik.

BACKGROUND: In cholesteatoma surgery the use of autogenous ossicles for restoration of sound conduction is often limited because of ingrowth of matrix epithelia into the ossicular bone. In an attempt to eliminated these epithelial cells we tested extracorporal high-pressure hydrostatic treatment as a new method for devitalizing the bone but maintaining its structure. METHODS: The inpact of different high hydrostatic pressures either on single cell suspensions of fibroblasts and osteoblasts, or on cells in ex-vivo ossicles chain was examined with different methods (quantitative proceedings, live/dead assay). Additional electron microscopic investigations illustrate the influence of high hydrostatic pressure treatment on cell suspensions of osteoblasts. RESULTS: High hydrostatic pressure between 150 MPa and 250 MPa showed no effect to cellular material. A safe elimination of cell growth was found after an application of pressures at or above 400 MPa. The electron microscopic investigations illustrate clearly the destruction of cellular membranes after high hydrostatic pressure treatment. CONCLUSIONS: These findings give hope that after extracorporal high hydrostatic pressure therapy autogenious ossicles might be used for middle ear recontructions even if they had contact with the cholesteatoma matrix or even were infitrated by keratinized squamous cell epithelia.

[Long-term changes in peripheral blood leukocyte and lymphocyte populations in ENT-carcinoma patients. A flow cytometric study in 346 ENT-carcinoma patients and 31 healthy controls]. / Veränderungen von peripheren Blutzellpopulationen bei HNO-Karzinompatienten. Eine flowzytometrische Studie mit 346 akut erkrankten und therapierten Patienten bis 20 Jahre nach Abschluss der Therapie und 31 Kontrollpersonen.

BACKGROUND AND AIM: The aim of this investigation was the quantification of leukocyte/lymphocyte populations in the peripheral blood of ENT-carcinoma patients before and long after therapy. PROBANDS AND METHOD: PBL T-lymphocytes and NK-cells were examined in 346 patients and 31 controls using flow cytometry. In 248 participants additional populations of leukocytes, monocytes, granulocytes, lymphocytes in toto, CD4+- and CD8+-lymphocytes, CD4+8+-lymphocytes, B-lymphocytes, activated T-lymphocytes, NK-cells and CD3+56+-T-lymphocytes were studied. RESULTS: We demonstrated a long-term reduction in T-lymphocytes (CD4+-lymphocytes) in patients more than 10 years after receiving therapy, caused mainly, but not solely, by radio/chemotherapy. We also showed a long-term, significant increase in NK-cells after more than 10 years in patients following therapy without renewed carcinoma in comparison to controls, patients prior to therapy or patients with a recurrence of carcinoma. CONCLUSIONS: Due to long-term deficits in CD4+-lymphocytes, and considering the possible protective effect of NK-cells in treated patients, an immune-supportive therapy is recommended.

[In vitro culture of cells from respiratory mucosa on foils of collagen, poly-L-lactide (PLLA) and poly-3-hydroxy-butyrate (PHB)]. / In-vitro-Kultivierung von Zellen der respiratorischen Schleimhaut auf Matrizes aus Kollagen, Poly-L-Laktid (PLLA) und Polyhydroxybuttersäure (PHB).

BACKGROUND: The replacement of respiratory mucosa after surgical resections at different locations in the ENT-field (trachea, nasal septum, sinus maxillaris) seems to be essential or at least of great benefit for patients. Presently a satisfying solution for this challenge does not exist. Therefore we have analysed the growth of cells from respiratory mucosa on different matrices. METHODS: Cell cultures are initiated mainly by growing out cells from tissue pieces but also by seeding of cells after enzymatic dissociation (sequential trypsinization) of mucosa. Cells were cultured with serum-containing and serum-free media on 3 different foils: made of collagen, of Poly-L-lactic acid (PLLA) and Poly-hydroxybutyric acid (PHB). Culturing time was on average about 4 - 5 weeks. RESULTS: On all tested materials fibroblasts and epithelial cells have grown in principle. PLLA was the material with best properties concerning the aim of this study whereas culturing of cells on PHB only happens after surface modification by amino-functionalisation with plasma treatment. Visualisation of cells on materials of collagen could not realised by light-microscopy due to the 3-dimensional structure and the optical properties of this material. Here the cultures were analysed by cell membrane staining and by REM. We could not find a differentiation of epithelial cells with beating cilia 6 weeks after starting the culture. However 20 days after starting the culture on PLLA (good conditions for observation with light-microscope) cells with beating cilia could be observed, in our opinion resulting from dissociated cells from tissue pieces and not from proliferated cells. CONCLUSIONS: In principle the analysed materials are useful for the culturing of cells from respiratory mucosa. However, for obtaining differentiated epithelial cells the culture conditions have to be modified.

[Influence of rhinologic usual and unusual drugs on fibroblasts from nasal polyps in cell culture]. / Verhalten von Fibroblasten aus Nasenpolypen in Zellkultur nach Applikation üblicher Rhinologika und unüblicher Medikamente unterschiedlicher Wirkstoffgruppen.

BACKGROUND: Nasal polyposis is treated by surgery and/or by medication but in parts without permanent remission. Fibroblasts and their proliferation are involved in the complex mechanism of polyp genesis. Therefore we have analysed the influence of 12 medications on fibroblasts from nasal polyps growing in vitro. METHOD: Nasal polyps, obtained during usual surgical procedure, are enzymatically digested and cultured in serum containing media. The growing cells are identified as fibroblasts using flow cytometry with a AS02-FITC antibody (Dianova). The analysis is achieved with 5 - 6 different fibroblast cultures in each medicament tested, mostly using concentrations of the active substance from 0.006 to 1.333 mg/ml. The fibroblasts are cultured 4 days in the presence of active substances or as controls. Finally the cells are trypsinated and counted. RESULTS: Mometason, Beclomethason, Fluticason, Verapamil and Timolol are the group with the strongest reduction of fibroblasts. Mometason shows a reduction to 6 % of controls at a concentration of 30 micro g/ml whereas the reduction at this concentration amounts to 30 - 60 % in the other members of this group. Mesazalin, Methylprednisolone and Pentoxifylline demonstrate the smallest influence; Prednisolon-21-hydrogen-succinate, Pilocarpin, Piroxicam and Diclofenac show an effect on a middle level. CONCLUSIONS: A strong reduction of fibroblasts from nasal polyps in vitro is possible with usual rhinological medicaments but also with unusual substances in this field.

Anesthesia changes frequency tuning of neurons in the rat primary auditory cortex.

The vast majority of investigations on central auditory processing so far were conducted under the influence of an anesthetic agent. It remains unclear, however, to what extend even basic response properties of central auditory neurons are influenced by this experimental manipulation. We used a combination of chronic recording in unrestrained animals, computer-controlled randomized acoustic stimulation, and statistical evaluation of responses to directly compare the response characteristics of single neurons in the awake and anesthetized state. Thereby we were able to quantify the effects of pentobarbital/chloral hydrate anesthesia (Equithesin) on rat auditory cortical neurons. During Equithesin anesthesia, only a portion of central neurons were active and some of their basic response properties were changed. Only 29% of the neurons still had a frequency response area. Their tuning sharpness was increased under anesthesia. Most changes are consistent with an enhancement of inhibitory influences during Equithesin anesthesia. Thus when describing response properties of central auditory neurons, the animal's anesthetic state has to be taken into account.

Afferent and efferent connections of the ventrolateral tegmental area in the rat.

The present study examined the organization of afferent and efferent connections of the rat ventrolateral tegmental area (VLTg) by employing the retrograde and anterograde axonal transport of Fluorogold and Phaseolus vulgaris-leucoagglutinin, respectively. Our interest was focused on whether the anatomical connections of the VLTg would provide evidence as to the involvement of this reticular area in audiomotor behavior. Our retrograde experiments revealed that minor inputs to the VLTg arise in various telencephalic structures, including the cerebral cortex. Stronger projections originate in the lateral preoptic area, the zona incerta, the nucleus of the posterior commissure and some other thalamic areas, the lateral substantia nigra, the deep layers of the superior colliculus, the dorsal and lateral central gray, the deep mesencephalic nucleus, the paralemniscal zone, the intercollicular nucleus, the external cortex of the inferior colliculus, the oral and caudal pontine reticular nucleus, the deep cerebellar nuclei, the gigantocellular and lateral paragigantocellular reticular nuclei, the prepositus hypoglossal nucleus, the spinal trigeminal nuclei, and the intermediate layers of the spinal cord. Most importantly, we disclosed strong auditory afferents arising in the dorsal and ventral cochlear nuclei and in the cochlear root nucleus. The efferent projections of the VLTg were found to be less widespread. Telencephalic structures do not receive any input from the VLTg. Moderate projections were seen to diencephalic reticular areas, the zona incerta, the nucleus of the posterior commissure, and to various other thalamic areas. The major VLTg projections terminate in the deep layers of the superior colliculus, the deep mesencephalic nucleus, the intercollicular nucleus and external cortex of the inferior colliculus, the oral and caudal pontine reticular nucleus, the gigantocellular and lateral paragigantocellular reticular nuclei, and in the medial column of the facial nucleus. From our data, we conclude that the VLTg might play a role in sensorimotor behavior.

[Are the products of CD44 exons v5 and v6 markers for metastasis of laryngeal carcinomas?]. / Sind die Produkte der Exons v5 und v6 von CD44 Marker für die Metastasierung von Larynxkarzinomen?

BACKGROUND: The transmembrane glycoprotein CD44 is referred to by many names, which are related to the polymorphism of this molecule. There are at least 10 different versions of the CD44 molecule. This polymorphism results from the insertion of extra domains into the extracellular part of the molecule and from different glycolization. These extra domains are coded by variable exons in the gene of CD44, which can be alternatively spliced. Some authors have postulated a link between expression of whole CD44 or some special molecule versions (often with the product of exon v6) on carcinoma cells and the potential of metastatic spread. The aim of our investigation was to look for this connection in larynx carcinomas. METHOD: We have tested 28 larynx carcinomas without metastases, 26 with metastases, and 20 lymph node metastases from larynx carcinomas with antibodies against the products of exon v5 and v6 in immunohistochemical studies of paraffin sections. RESULTS: In all cases we observed nearly the same staining intensity of exon v5 and v6 products. There was no significant difference between carcinomas with and without metastases or the lymph node metastases. However, a strong difference of reaction was found between the carcinoma cells of the outer proliferative tumor areas and the inner tumor areas, which were cornified in parts. Whereas the first mentioned cells generally stained very intensively, the latter showed only a slight reaction or none at all. CONCLUSIONS: In our opinion, CD44 v5 and v6 appear to be valuable markers of proliferation although we could not establish a strong connection to metastatic behavior.

Effect of the middle ear reflex on sound transmission to the inner ear of rat.

The effect of the acoustic middle ear reflex (MER) was quantified using electrodes chronically implanted in the middle ears of rats. Cochlear microphonics (CM) and middle ear muscle EMG were measured under light Ketamin anesthesia after stimulation with tone pulses of 5-20 kHz ranging between 75 and 120 dB SPL. With increasing intensity, the CM measured before the onset of the MER increased to a maximum amplitude and then decreased with higher SPLs. At 10 kHz this maximum was reached at 95 dB SPL, for other stimulus frequencies at higher SPLs. After a latency of 10-20 ms, CM to 10 kHz stimuli of 80-95 dB SPL were decreased by the attenuating action of the MER. The lowest threshold of the MER was also measured at 10 kHz (77 dB SPL in the mean). To stimuli greater than 100 dB SPL after a latency of 6-10 ms, the CM amplitude was increased. That this CM increase to intense stimuli is caused by the action of the MER was confirmed by control experiments such as cutting the tendons of the middle ear muscles. The CM decrease to stimuli below 100 dB SPL, as well as the increase to very intense stimuli, can be explained by sound attenuation caused by the MER, together with the nonlinear dependence of CM amplitude on stimulus level. The observed shift of the maxima of the CM input-output function by the MER to higher stimulus levels probably indicates an increase of the dynamic range of the ear.

Responses to exponential frequency modulations in the rat inferior colliculus.

We examined responses to pure tones and exponentially frequency-modulated (FM) stimuli in the inferior colliculus of ketamine anesthetized rats. All units responded to both pure-tone and FM stimulation: units responding selectively to FM stimuli were not found. The comparison between responses to many different FM sweeps revealed that activity was elicited when the instantaneous frequency of a FM sweep entered the unit's pure-tone tuning curve. Units were tuned to the rate of frequency modulation. Most modulation rate transfer functions had bandpass characteristics. Best modulation rates covered a range from 4.8 to 1904 octaves/s with more than 90% between 10 and 400 octaves/s. In contrast to previous studies, modulation direction was not coded in unit responses and only few units demonstrated a weak change in response strength when sweep direction was altered. This is at least partly attributable to the FM stimulus design which, in the present study, was adapted to the logarithmic frequency representation in the rat auditory system and carefully matched to the units' pure-tone responses area. In spite of the close relationship between pure tone and FM response behavior, modulation rate tuning cannot be completely explained on the basis of the units' pure-tone responses.

GABA alters the discharge pattern of chopper neurons in the rat ventral cochlear nucleus.

The effect of microiontophoretically applied gamma-aminobutyric acid (GABA) on chopper neurons in the ventral cochlear nucleus of the rat is described. The predominantly inhibitory effect of GABA resulted in a change of the regular discharge pattern. The interspike interval increased and the pattern became less regular as indicated by an increase of its coefficient of variation. These results suggest that the release of GABA may be responsible for the transient chopper behavior of some neurons which loose their regular discharge pattern within 20 ms after onset of the response to pure-tone stimulation.

Temporal coding of amplitude and frequency modulation in the rat auditory cortex.

The rat primary auditory cortex was explored for neuronal responses to pure tones and sinusoidally amplitude-modulated (SAM) and frequency-modulated (SFM) stimuli. Units showed phase-locked responses to SAM stimulation (55%) and SFM stimulation (80%), with modulation frequencies up to 18 Hz. Tuning characteristics to the modulation frequency were mainly band-pass with best modulation frequencies (BMFs) between 4 and 15 Hz. Units with synchronized activity to SFM stimulation showed three response types with respect to the direction of the frequency modulation: 52% were selective to the upward direction, 30% to the downward direction, and 18% had no preference. Triangular frequency modulations were used to test if units were tuned to specific modulation frequencies or to specific rates of frequency change. In the vast majority of units tested the response characteristics were strongly influenced by varying the modulation frequency, whereas varying the rate of frequency change had little effect in the stimulus range used. Units that showed phase-locked responses to SAM and SFM stimulation had similar activity patterns in response to both types of stimuli. BMFs for SAM and SFM stimulation were significantly correlated. Intrinsic oscillations of up to 20 Hz could be seen in the spontaneous activity and after the stimuli independent of the stimulus type. Oscillation frequencies were significantly correlated with the BMFs of the respective units. The results are discussed in terms of a mechanism for periodicity detection based on a temporal code. This could be important for the recognition of complex acoustic signals.

GABA can improve acoustic contrast in the rat ventral cochlear nucleus.

The effect of microiontophoretically applied gamma-aminobutyric acid (GABA) and its agonists and antagonists on the response pattern of single units in the ventral cochlear nucleus (VCN) of the rat was examined in order to study GABA's physiological function in auditory processing. The effects of the drugs were judged by changes of spontaneous and sound-evoked activity in peristimulus-time histograms (PSTHs) of at least 20 consecutive presentations of acoustic stimuli. GABA inhibited the discharge activity of the majority of neurons. All response types found in the VCN except onset-I responders were sensitive to GABA. The GABAergic inhibition is most probably mediated by GABAA receptors, since the GABAA-receptor agonist muscimol, but not the GABAB-receptor agonist baclofen, mimicked the effect of GABA. The GABAA-receptor antagonists, bicuculline and picrotoxin, had an excitatory effect on the neurons' spontaneous activity, suggesting a tonic endogeneous release of GABA which exerts a permanent inhibition on VCN neurons. Although inhibitory, iontophoresis of GABA emphasized the response to stimulus onset in the PSTHs by means of a stronger inhibition of spontaneous activity. When using iontophoretical currents which did not suppress the neuronal activity completely, a strong inhibition of spontaneous activity was accompanied by only a small inhibition of tone-evoked activity. Under these conditions, the response to tone onset was frequently not inhibited at all. Therefore, GABA's physiological function is possibly to improve the contrast between transient acoustic signals and ongoing background activity. In order to test this hypothesis, the test tone was masked by continuous background noise. Indeed, GABA reduced the noise-evoked discharge more than the tone-evoked discharge, leaving the onset peak in the PSTHs almost unchanged. Thus, GABAergic input improves the signal-to-noise ratio for acoustic transients in VCN neurons. Our data suggest that a functional role of GABA in the VCN is to act as a transmitter within a descending inhibitory feedback loop of the auditory brainstem which serves to improve the transmission of relevant acoustic signals in constant background noise.

Substance P and other putative transmitters modulate the activity of reticular pontine neurons: an electrophysiological and immunohistochemical study.

In this study we investigated the effects of possible modulatory transmitters on acoustically responsive neurons of the caudal pontine reticular nucleus (PnC). From previous work in our laboratory it has been suggested that the acoustically responsive giant neurons of this nucleus are the sensorimotor interface mediating the acoustic startle response. Furthermore they are the site of some of the modulatory influence impinging on this response. Besides a possibly glutamatergic excitation from the amygdala a cholinergic input from the midbrain has been described which may use substance P as cotransmitter. Therefore we used electrophysiological and histochemical methods to study this possible modulatory influence in the caudal pontine reticular nucleus. In the first part of this study we recorded extracellularly from single units in the PnC in vivo and studied the effects of iontophoretically applied transmitters. Substance P elicited a long lasting excitation. This excitatory effect of SP was potentiated by acetyl-beta-methylcholine (AMCh, an acetylcholine agonist), whereas single application of AMCh showed no uniform response. Glutamate elicited a potent brief excitation, while application of GABA showed a potent brief inhibition of PnC neurons. In the second part of this study we employed immunoperoxidase staining for substance P, which revealed a fairly dense network of substance P-immunoreactive (SP-ir) fibers in the lateral and ventral aspects of the PnC. Combining retrograde tracing and immunocytochemistry for substance P, we demonstrated that the SP-ir axons in the PnC originate mainly in the laterodorsal tegmental nucleus. We therefore conclude that activation of the laterodorsal tegmental nucleus may facilitate the acoustic startle response by a long lasting excitation of neurons in the caudal pontine reticular nucleus.

Discrimination of two-wavefront echoes by the big brown bat, Eptesicus fuscus: behavioral experiments and receiver simulations.

1. Echolocating bats (Eptesicus fuscus) were trained to discriminate between simulated targets consisting of one or two echo-wavefronts with internal time delays of up to 100 microseconds. Spectral and temporal properties and total signal energy of the targets were evaluated and predictions for performances of bats derived from receiver models were compared with measured performances. 2. Eptesicus fuscus was able to discriminate a one-wavefront target from two-wavefront targets with distinct internal time delays (12 microseconds, 32-40 microseconds and 52-100 microseconds). Performance was not affected by changes in total signal energy. Bats also successfully discriminated between two-wavefront targets with different internal time delays. 3. Performance predicted from differences in total energy between targets did not match the measured performance, indicating that bats did not rely on total echo energy. This finding is also supported by the behavioral data. Performance predicted from spectral and temporal receiver models both matched the measured performance and, therefore, neither one of these models can be favored over the other. 4. The behavioral data suggest that Eptesicus fuscus did not transform echo information into estimates of target range separation and, therefore, did not perceive the two wavefronts of each simulated two-wavefront echo as two separate targets.

Serotonin modulates auditory information processing in the cochlear nucleus of the rat.

The effect of iontophoretic application of serotonin (5-HT) was studied in neurons of the cochlear nucleus in the rat. 5-HT inhibited the spontaneous activity in 71%, and the tone-evoked activity in 32% of the neurons. We also observed an excitatory effect, with a longer latency than that of the inhibition, in 40% of the neurons. In some neurons 5-HT had both inhibitory and excitatory effects. Neurons with different response types seem to have different sensitivities to 5-HT. As the effects of 5-HT were generally weaker than those of other putative neurotransmitters, it probably has only a small modulatory influence on auditory processing.

The mesencephalic locomotor region is activated during the auditory startle response of the unrestrained rat.

We describe an acoustically evoked potential in the midbrain of the rat which occurred in conjunction with the auditory startle response, 'startle correlated potential'. This potential had a variable latency to the onset of the startle-eliciting acoustic stimuli, but was precisely coupled to the startle response in the electromyogram (EMG) of the temporal muscle which was simultaneously recorded. We tried to localize the source of this potential by recording evoked potentials at different recording sites in individual awake and unrestrained rats using a specially constructed microdrive. The potential may be generated in part by neurons in the region of the pedunculopontine tegmental nucleus, lying within the electrophysiologically defined mesencephalic locomotor region (MLR). We suggest, therefore, that the startle correlated potential reflects the activation of the MLR during the startle response. Timing calculations make it unlikely that the startle correlated potential is generated by a sensorimotor relay within the primary startle circuit which produced a fast startle twitch in the temporal muscle. Instead, the startle correlated potential probably reflects the involvement of the MLR in a later secondary startle response or in response modulation, e.g. habituation. In our opinion the most interesting possibility is that the MLR could be activated during a startle response to inhibit and reset the current motor program.

Topography of projections from the auditory cortex to the inferior colliculus in the rat.

We examined the organization of descending projections from auditory and adjacent cortical areas to the inferior colliculus (IC) in the rat by using the retrograde and anterograde transport of wheat germ agglutinin-horseradish peroxidase. Small tracer injections were placed into cytologically defined subnuclei of the IC. On the basis of the resulting pattern of retrogradely labeled neurons in the cortex, different cortical areas and fields were defined. Two secondary areas located ventrocaudally (Te2) and ventrally (Te3) to the primary auditory area (Te1) were delineated. The primary auditory area was subdivided into a posterior (Te1.p), a medial (Te1.m), and an anterior (Te1.a) auditory field. In addition, we outlined an area located rostrally to the auditory areas comprising a part of the secondary somatosensory cortex, as well as a dorsal belt surrounding dorsally the auditory areas. The following basic patterns of corticocollicular projections are revealed: 1) layers 2 and 3 of the dorsal cortex of the IC (DC2, DC3) are differentially innervated by the primary auditory fields (Te1.p and Te1.a project bilaterally to DC2, while Te1.m projects bilaterally and in topographical order to DC3); cells in Te1.m, arranged in caudal to rostral sequence, project to corresponding loci in DC3 arranged from dorsolateral to ventromedial; 2) the fibrocellular capsule of the IC, comprising layer 1 of the dorsal and external cortex of the IC, receives input from the secondary auditory area Te2; 3) layers 2 and 3 of the external cortex of the IC are only weakly innervated by the primary and secondary auditory cortex; 4) the intercollicular zone receives its major input from the secondary auditory area Te3, the secondary somatosensory cortex, and the dorsal belt; and 5) finally, the central nucleus of the IC receives no input from the temporal cortex at all. Our results demonstrate that the corticocollicular projections are highly organized. These pathways may modulate auditory processing in different functional circuits of the inferior colliculus.

Startle responses measured in muscles innervated by facial and trigeminal nerves show common modulation.

Electromyographic (EMG) potentials of several head muscles were recorded simultaneously in freely moving rats with chronically implanted electrodes. The startle responses of m. temporalis, m. levator auris, and m. levator labii superior were compared. All muscles showed a parallel decrease in latency and an increase in response elicitability and amplitude with an increase in stimulus intensity. A significant latency difference of about 1 ms existed between m. levator auris and m. temporalis. The shortest latency of the EMG response in m. levator auris was 5.5 ms (110 dB SPL). A common fluctuation in response amplitude and latency was found in simultaneous recordings of muscles innervated by the facial and trigeminal nerve, respectively. This shows a common modulatory input to the startle pathway to the cranial motor nuclei.

Range estimation by echolocation in the bat Eptesicus fuscus: trading of phase versus time cues.

Bats of the species Eptesicus fuscus have been trained to discriminate a stationary simulated target from a target with a virtual distance that jitters from sound to sound. Similar to Simmons [Science 207, 1336-1338 (1979)], a jitter-detection threshold below 1 microsecond was found. However, Simmons' decreased performance at a time delay jitter of 30 microseconds could not be replicated, a critical feature used to postulate the idea that bats employ a coherent cross-correlation receiver for ranging. Such a receiver uses all phase information in the signal for delay estimation and therefore will be biased by phase manipulations. To test for such a bias, a phase jitter of +/- 45 degrees and a time jitter in the echo were overlaid. It was not found that there was a combination of both where their effects canceled. Full phase information is thus not used in delay estimation. However, bats were able to detect a pure phase jitter, e.g., polarity inversion of the signal. Bats could also detect phase jitter in the presence of randomized time jitter and vice versa. Phase jitter and time jitter, therefore, are separable features for a bat. The underlying physiological mechanism is not clear.

Distribution of cochlear efferents and olivo-collicular neurons in the brainstem of rat and guinea pig. A double labeling study with fluorescent tracers.

In rat and guinea pig, cochlear efferents to the two ears were labeled simultaneously with different fluorescent tracers. It was found that in both species only few (1-3%) olivo-cochlear neurons were double-labeled and project to both cochleae. In most periolivary regions large olivocochlear neurons (OCN) projecting to the ipsilateral and contralateral side are intermingled and form a continuous cell column between the facial nucleus and lateral lemniscus. In a second series of experiments in rat, cochlear efferents and ascending olivo-collicular neurons were labeled. Olivo-cochlear and olivo-collicular neurons are intermingled in the lateral superior olive (LSO) and in the ventromedial periolivary region. No double-labeled neurons were found that project to the cochlea and the inferior colliculus.