Medial Superior Olive Neurons Research Articles

The Mammalian Interaural Time Difference Detection Circuit Is Differentially Controlled by GABAB Receptors during Development

Throughout development GABA(B) receptors (GABA(B)Rs) are widely expressed in the mammalian brain. In mature auditory brainstem neurons, GABA(B)Rs are involved in the short-term regulation of the strength and dynamics of excitatory and inhibitory inputs, thus modulating sound analysis. During development, GABA(B)Rs also contribute to long-term changes in input strength. Using a combination of whole-cell patch-clamp recordings in acute brain slices and immunostainings in gerbils, we characterized developmental changes in GABA(B)R-mediated regulation of synaptic inputs to neurons in the medial superior olive (MSO), an auditory brainstem nucleus that analyzes interaural time differences (ITDs). Here, we show that, before hearing onset, GABA(B)R-mediated depression of transmitter release is much stronger for excitation than inhibition, whereas in mature animals GABA(B)Rs mainly control the inhibition. During the same developmental period, GABA(B)R immunoreactivity shifts from the dendritic to the somatic region of the MSO. Furthermore, only before hearing onset (postnatal day 12), stimulation of the fibers originating in the medial and the lateral nucleus of the trapezoid body (MNTB and LNTB) activates GABA(B)Rs on both the inhibitory and the excitatory inputs. After hearing onset, GAD65-positive endings devoid of glycine transporter reactivity suggest GABA release from sources other than the MNTB and LNTB. At this age, pharmacological increase of spontaneous synaptic release activates GABA(B)Rs only on the inhibitory inputs. This indicates not only a profound inhibitory effect of GABA(B)Rs on the major inputs to MSO neurons in neonatal animals but also a direct modulatory role of GABA(B)Rs for ITD analysis in the MSO of adult animals.

Control of submillisecond synaptic timing in binaural coincidence detectors by Kv1 channels

Neurons in the medial superior olive process sound-localization cues via binaural coincidence detection, in which excitatory synaptic inputs from each ear are segregated onto different branches of a bipolar dendritic structure and summed at the soma and axon with submillisecond time resolution. Although synaptic timing and dynamics critically shape this computation, synaptic interactions with intrinsic ion channels have received less attention. Using paired somatic and dendritic patch-clamp recordings in gerbil brainstem slices together with compartmental modeling, we found that activation of K(v)1 channels by dendritic excitatory postsynaptic potentials (EPSPs) accelerated membrane repolarization in a voltage-dependent manner and actively improved the time resolution of synaptic integration. We found that a somatically biased gradient of K(v)1 channels underlies the degree of compensation for passive cable filtering during propagation of EPSPs in dendrites. Thus, both the spatial distribution and properties of K(v)1 channels are important for preserving binaural synaptic timing.

Perisomatic Voltage-Gated Sodium Channels Actively Maintain Linear Synaptic Integration in Principal Neurons of the Medial Superior Olive

Principal neurons of the medial superior olive (MSO) compute azimuthal sound location by integrating phase-locked inputs from each ear. While previous experimental and modeling studies have proposed that voltage-gated sodium channels (VGSCs) play an important role in synaptic integration in the MSO, these studies appear at odds with the unusually weak active backpropagation of action potentials into the soma and dendrites. To understand the spatial localization and biophysical properties of VGSCs, we isolated sodium currents in MSO principal neurons in gerbil brainstem slices. Nucleated and cell-attached patches revealed that VGSC density at the soma is comparable to that of many other neuron types, but channel expression is largely absent from the dendrites. Further, while somatic VGSCs activated with conventional voltage dependence (V(1/2) = -30 mV), they exhibited an unusually negative range of steady-state inactivation (V(1/2) = -77 mV), leaving approximately 92% of VGSCs inactivated at the resting potential (approximately -58 mV). In current-clamp experiments, non-inactivated VGSCs were sufficient to amplify subthreshold EPSPs near action potential threshold, counterbalancing the suppression of EPSP peaks by low voltage-activated potassium channels. EPSP amplification was restricted to the perisomatic region of the neuron, and relatively insensitive to preceding inhibition. Finally, computational modeling showed that the exclusion of VGSCs from the dendrites equalizes somatic EPSP amplification across synaptic locations and lowered the threshold for bilateral versus unilateral excitatory synaptic inputs. Together, these findings suggest that the pattern of sodium channel expression in MSO neurons contributes to these neurons' selectivity for coincident binaural inputs.

Enhancing sensitivity to interaural time differences at high modulation rates by introducing temporal jitter

Sensitivity to interaural time differences (ITDs) in high-frequency bandpass-filtered periodic and aperiodic (jittered) pulse trains was tested at a nominal pulse rate of 600 pulses per second (pps). It was found that random binaurally-synchronized jitter of the pulse timing significantly increases ITD sensitivity. A second experiment studied the effects of rate and place. ITD sensitivity for jittered 1200-pps pulse trains was significantly higher than for periodic 600-pps pulse trains, and there was a relatively small effect of place. Furthermore, it could be concluded from this experiment that listeners were not solely benefiting from the longest interpulse intervals (IPIs) and the instances of reduced rate by adding jitter, because the two types of pulse trains had the same longest IPI. The effect of jitter was studied using a physiologically-based model of auditory nerve and brainstem (medial superior olive neurons). It was found that the random timing of the jittered pulses increased firing synchrony in the auditory periphery, which caused an improved rate-ITD tuning for the 600-pps pulse trains. These results suggest that a recovery from binaural adaptation induced by temporal jitter is possibly related to changes in the temporal firing pattern, not spectral changes.

From quantification of 3D morphology of coincidence detector neurons in the MSO to a multi-compartmental model

In the medial superior olive (MSO), neurons compute the azimuthal location of low frequency sound sources by a temporally precise mechanism of coincidence detection. This type of neuronal processing has been subject to various model predictions based on in vivo and in vitro data obtained in mammalian MSO and an avian analog brain structure. It is assumed that dendritic morphology of MSO neurons affects this computational process. However, few quantitative data about the morphology of these neuronal coincidence detectors are available from mammals, limiting theoretical approaches. We used single cell electroporation, microscopic reconstruction and compartmentalization to extract anatomical parameters of MSO neurons and quantitatively describe their morphology and their development between postnatal day 9 and 36. The dendritic arborization of higher order dendrites decreases between postnatal day 9 and 21, whereas the dendritic radius increased until P27. The developmental profile of the morphology of MSO neurons shows that maturation is reached two weeks after hearing onset. In general, we find that at postnatal days older than P27 the neurons of the gerbil MSO are bipolar, morphologically compact, cylinder-like cells with axons originating from the soma. The obtained geometry of these cells was then used to establish multi-compartmental models to quantify the influence of morphological and developmental changes on the integration of synaptic currents. To increase computational and programming efficiency of the simulations, we developed a Python-based object-oriented library. from Eighteenth Annual Computational Neuroscience Meeting: CNS*2009 Berlin, Germany. 18–23 July 2009

Accurate Sound Localization in Reverberant Environments Is Mediated by Robust Encoding of Spatial Cues in the Auditory Midbrain

In reverberant environments, acoustic reflections interfere with the direct sound arriving at a listener's ears, distorting the spatial cues for sound localization. Yet, human listeners have little difficulty localizing sounds in most settings. Because reverberant energy builds up over time, the source location is represented relatively faithfully during the early portion of a sound, but this representation becomes increasingly degraded later in the stimulus. We show that the directional sensitivity of single neurons in the auditory midbrain of anesthetized cats follows a similar time course, although onset dominance in temporal response patterns results in more robust directional sensitivity than expected, suggesting a simple mechanism for improving directional sensitivity in reverberation. In parallel behavioral experiments, we demonstrate that human lateralization judgments are consistent with predictions from a population rate model decoding the observed midbrain responses, suggesting a subcortical origin for robust sound localization in reverberant environments.

Experience‐dependent refinement of the inhibitory axons projecting to the medial superior olive

Neurons in the medial superior olive (MSO) analyze interaural time differences (ITDs) by comparing the arrival times of the two excitatory inputs from each ear using a coincidence detection mechanism. They also receive a prominent inhibitory, glycinergic projection from the ipsilateral medial nucleus of the trapezoid body (MNTB), which contributes to the fine-tuning of ITD analysis. Here, we investigated developmental changes of the axonal arborisation pattern of single Microruby-labeled MNTB neurons projecting to the MSO region. During the first 2 weeks after hearing onset, the axonal arborisation of MNTB neurons was significantly refined resulting in a narrowed projection area across the tonotopic axis of the MSO and a redistribution of the axonal endsegments to a mostly somatic location. Rearing the animals in omnidirectional noise prevented the structural changes of single MNTB projections. These results indicate that the functional elimination of inhibitory inputs on MSO neurons after hearing onset, as described previously, is paralleled by a structural, site-specific refinement of the inputs and is dependent on the normal acoustic experience of the animal.

Interaural Time Difference Processing in the Mammalian Medial Superior Olive: The Role of Glycinergic Inhibition

The dominant cue for localization of low-frequency sounds are microsecond differences in the time-of-arrival of sounds at the two ears [interaural time difference (ITD)]. In mammals, ITD sensitivity is established in the medial superior olive (MSO) by coincidence detection of excitatory inputs from both ears. Hence the relative delay of the binaural inputs is crucial for adjusting ITD sensitivity in MSO cells. How these delays are constructed is, however, still unknown. Specifically, the question of whether inhibitory inputs are involved in timing the net excitation in MSO cells, and if so how, is controversial. These inhibitory inputs derive from the nuclei of the trapezoid body, which have physiological and structural specializations for high-fidelity temporal transmission, raising the possibility that well timed inhibition is involved in tuning ITD sensitivity. Here, we present physiological and pharmacological data from in vivo extracellular MSO recordings in anesthetized gerbils. Reversible blockade of synaptic inhibition by iontophoretic application of the glycine antagonist strychnine increased firing rates and significantly shifted ITD sensitivity of MSO neurons. This indicates that glycinergic inhibition plays a major role in tuning the delays of binaural excitation. We also tonically applied glycine, which lowered firing rates but also shifted ITD sensitivity in a way analogous to strychnine. Hence tonic glycine application experimentally decoupled the effect of inhibition from the timing of its inputs. We conclude that, for proper ITD processing, not only is inhibition necessary, but it must also be precisely timed.

Morphological features of the medial superior olive in autism

Autism is a psychosocial disorder clinically characterized by social difficulties, impairment in communication skills and repetitive behavioral patterns. Despite the increasing reported incidence of autism, the neurobiology of this disorder is poorly understood. However, researchers have uncovered numerous structural anomalies in the brainstem, cerebellum and forebrain of autistic individuals and there is substantial support for the association of hearing deficits with autism. In an effort to discover an anatomical correlate for the functional auditory deficits found in autism, we examined the SOC, a group of brainstem nuclei that function in sound source localization, in post-mortem brain tissue from autistic individuals. The neurons of the medial superior olive (MSO), an SOC nucleus, display a precise geometric organization essential for detection of timing differences between the two ears. We examined the architecture of the MSO in five autistic brains (ages 8 to 32 years) and two age-matched controls (ages 26 and 29 years) and found a significant disruption in the morphology of MSO neurons in autistic brains, involving cell body shape and orientation. The results from this study provide evidence on the cellular level that may help to explain the hearing difficulties associated with autism.

Interaural time difference processing in the mammalian medial superior olive

The dominant cue for localization of low-frequency sounds are microsecond differences in the time-of-arrival of sounds at the two ears [interaural time difference (ITD)]. In mammals, ITD sensitivity is established in the medial superior olive (MSO) by coincidence detection of excitatory inputs from both ears. Hence the relative delay of the binaural inputs is crucial for adjusting ITD sensitivity in MSO cells. How these delays are constructed is, however, still unknown. Specifically, the question of whether inhibitory inputs are involved in timing the net excitation in MSO cells, and if so how, is controversial. These inhibitory inputs derive from the nuclei of the trapezoid body, which have physiological and structural specializations for high-fidelity temporal transmission, raising the possibility that well timed inhibition is involved in tuning ITD sensitivity. Here, we present physiological and pharmacological data from in vivo extracellular MSO recordings in anesthetized gerbils. Reversible blockade of synaptic inhibition by iontophoretic application of the glycine antagonist strychnine increased firing rates and significantly shifted ITD sensitivity of MSO neurons. This indicates that glycinergic inhibition plays a major role in tuning the delays of binaural excitation. We also tonically applied glycine, which lowered firing rates but also shifted ITD sensitivity in a way analogous to strychnine. Hence tonic glycine application experimentally decoupled the effect of inhibition from the timing of its inputs. We conclude that, for proper ITD processing, not only is inhibition necessary, but it must also be precisely timed.

Development of gerbil medial superior olive: integration of temporally delayed excitation and inhibition at physiological temperature.

The sensitivity of medial superior olive (MSO) neurons to tens of microsecond differences in interaural temporal delay (ITD) derives in part from their membrane electrical characteristics, kinetics and timing of excitatory and inhibitory inputs, and dendrite structure. However, maturation of these physiological and structural characteristics are little studied, especially in relationship to the onset of auditory experience. We showed, using brain slices at physiological temperature, that MSO neurons exhibited sensitivity to simulated temporally delayed (TD) EPSCs (simEPSC), injected through the recording electrode, by the initial phase of hearing onset at P10, and TD sensitivity was reduced by block of low threshold potassium channels. The spike generation mechanism matured between P10 and P16 to support TD sensitivity to adult-like excitatory stimuli (1-4 ms duration) by P14. IPSP duration was shorter at physiological temperature than reported for lower temperatures, was longer than EPSP duration at young ages, but approached the duration of EPSPs by P16, when hearing thresholds neared maturity. Dendrite branching became less complex over a more restricted time frame between P10 and P12. Because many physiological and structural properties approximated mature values between P14 and P16, we studied temporal integration of simEPSCs and IPSPs at P15. Only a narrow range of relative onset times (< 1 ms) yielded responses showing sensitivity to TD. We propose that shaping of excitatory circuitry to mediate TD sensitivity can begin before airborne sound is detectable, and that inhibitory inputs having suboptimal neural delays may then be pruned by cellular mechanisms activated by sensitivity to ITD.

Weak action potential backpropagation is associated with high‐frequency axonal firing capability in principal neurons of the gerbil medial superior olive

Principal neurons of the medial superior olive (MSO) convey azimuthal sound localization cues through modulation of their rate of action potential firing. Previous intracellular studies in vitro have shown that action potentials appear highly attenuated at the soma of MSO neurons, potentially reflecting specialized action potential initiation and/or a physically distant site of generation. To examine this more directly, we made dual patch-clamp recordings from MSO principal neurons in gerbil brainstem slices. Using somatic and dendritic whole-cell recordings, we show that graded action potentials at the soma are highly sensitive to the rate of rise of excitation and undergo strong attenuation in their backpropagation into the dendrites (length constant, 76 microm), particularly during strong dendritic excitation. Using paired somatic whole-cell and axonal loose-patch recordings, we show that action potentials recorded in the axon at distances > 25 microm are all-or-none, and uniform in amplitude even when action potentials appear graded at the soma. This proximal zone corresponded to the start of myelination in the axon, as assessed with immunocytochemical staining for myelin basic protein in single-labelled neurons. Finally, the axon was capable of sustaining remarkably high firing rates, with perfect entrainment occurring at frequencies of up to 1 kHz. Together, our findings show that action potential signalling in MSO principal neurons is highly secure, but shows a restricted invasion of the somatodendritic compartment of the cell. This restriction may be important for minimizing distortions in synaptic integration during the high frequencies of synaptic input encountered in the MSO.

Developmental pattern of three vesicular glutamate transporters in the rat superior olivary complex

Vesicular glutamate transporters (VGLUTs) mediate the packaging of the excitatory neurotransmitter glutamate into synaptic vesicles. Three VGLUT subtypes have been identified so far, which are differentially expressed in the brain. Here, we have investigated the spatiotemporal distribution of the three VGLUTs in the rat superior olivary complex (SOC), a prominent processing center, which receives strong glutamatergic inputs and which lies within the auditory brainstem. Immunoreactivity (ir) against all three VGLUTs was found in the SOC nuclei throughout development (postnatal days P0-P60). It was predominantly seen in axon terminals, although cytoplasmic labeling also occurred. Each transporter displayed a characteristic expression pattern. In the adult SOC, VGLUT1 labeling varied from strong in the medial nucleus of the trapezoid body, lateral superior olive, and medial superior olive (MSO) to moderate (ventral and lateral nuclei of the trapezoid body) to faint (superior paraolivary nucleus). VGLUT2-ir was moderate to strong throughout the SOC, whereas VGLUT3 was only weakly expressed. These results extend previous reports on co-localization of VGLUTs in the auditory brainstem. As in the adult, specific features were seen during development for all three transporters. Intensity increases and decreases occurred with both VGLUT1 and VGLUT3, whereas VGLUT2-ir remained moderately high throughout development. A striking result was obtained with VGLUT3, which was only transiently expressed in the different SOC nuclei between P0 and P12. A transient occurrence of VGLUT1-immunoreactive terminals on somata of MSO neurons was another striking finding. Our results imply a considerable amount of synaptic reorganization in the glutamatergic inputs to the SOC and suggest differential roles of VGLUTs during maturation and in adulthood.

Enhancement of Signal-to-Noise Ratio and Phase Locking for Small Inputs by a Low-Threshold Outward Current in Auditory Neurons

Neurons possess multiple voltage-dependent conductances specific for their function. To investigate how low-threshold outward currents improve the detection of small signals in a noisy background, we recorded from gerbil medial superior olivary (MSO) neurons in vitro. MSO neurons responded phasically, with a single spike to a step current injection. When bathed in dendrotoxin (DTX), most cells switched to tonic firing, suggesting that low-threshold potassium currents (I(KLT)) participated in shaping these phasic responses. Neurons were stimulated with a computer-generated steady barrage of random inputs, mimicking weak synaptic conductance transients (the "noise"), together with a larger but still subthreshold postsynaptic conductance, EPSG (the "signal"). DTX reduced the signal-to-noise ratio (SNR), defined as the ratio of probability to fire in response to the EPSG and the probability to fire spontaneously in response to noise. The reduction was mainly attributable to the increase of spontaneous firing in DTX. The spike-triggered reverse correlation indicated that, for spike generation, the neuron with I(KLT) required faster inward current transients. This narrow temporal integration window contributed to superior phase locking of firing to periodic stimuli before application of DTX. A computer model including Hodgkin-Huxley type conductances for spike generation and for I(KLT) (Rathouz and Trussell, 1998) showed similar response statistics. The dynamic low-threshold outward current increased SNR and the temporal precision of integration of weak subthreshold signals in auditory neurons by suppressing false positives.

Precise inhibition is essential for microsecond interaural time difference coding.

Microsecond differences in the arrival time of a sound at the two ears (interaural time differences, ITDs) are the main cue for localizing low-frequency sounds in space. Traditionally, ITDs are thought to be encoded by an array of coincidence-detector neurons, receiving excitatory inputs from the two ears via axons of variable length ('delay lines'), to create a topographic map of azimuthal auditory space. Compelling evidence for the existence of such a map in the mammalian lTD detector, the medial superior olive (MSO), however, is lacking. Equally puzzling is the role of a--temporally very precise glycine--mediated inhibitory input to MSO neurons. Using in vivo recordings from the MSO of the Mongolian gerbil, we found the responses of ITD-sensitive neurons to be inconsistent with the idea of a topographic map of auditory space. Moreover, local application of glycine and its antagonist strychnine by iontophoresis (through glass pipette electrodes, by means of an electric current) revealed that precisely timed glycine-controlled inhibition is a critical part of the mechanism by which the physiologically relevant range of ITDs is encoded in the MSO. A computer model, simulating the response of a coincidence-detector neuron with bilateral excitatory inputs and a temporally precise contralateral inhibitory input, supports this conclusion.

Medial superior olive of the big brown bat: neuronal responses to pure tones, amplitude modulations, and pulse trains.

The structure and function of the medial superior olive (MSO) is highly variable among mammals. In species with large heads and low-frequency hearing, MSO is adapted for processing interaural time differences. In some species with small heads and high-frequency hearing, the MSO is greatly reduced in size; in others, including those echolocating bats that have been examined, the MSO is large. Moreover, the MSO of bats appears to have undergone different functional specializations depending on the type of echolocation call used. The echolocation call of the mustached bat contains a prominent CF component, and its MSO is predominantly monaural; the free-tailed bat uses pure frequency-modulated calls, and its MSO is predominantly binaural. To further explore the relation of call structure to MSO properties, we recorded extracellularly from 97 single neurons in the MSO of the big brown bat, Eptesicus fuscus, a species whose echolocation call is intermediate between that of the mustached bat and the free-tailed bat. The best frequencies of MSO neurons in the big brown bat ranged from 11 to 79 kHz, spanning most of the audible range. Half of the neurons were monaural, excited by sound at the contralateral ear, while the other half showed evidence of binaural interactions, supporting the idea that the binaural characteristics of MSO neurons in the big brown bat are midway between those of the mustached bat and the free-tailed bat. Within the population of binaural neurons, the majority were excited by sound at the contralateral ear and inhibited by sound at the ipsilateral ear; only 21% were excited by sound at either ear. Discharge patterns were characterized as transient ON (37%), primary-like (33%), or transient OFF (23%). When presented with sinusoidally amplitude modulated tones, most neurons had low-pass filter characteristics with cutoffs between 100 and 300 Hz modulation frequency. For comparison with the sinusoidally modulated sounds, we presented trains of tone pips in which the pulse duration and interstimulus interval were varied. The results of these experiments indicated that it is not the modulation frequency but rather the interstimulus interval that determines the low-pass filter characteristics of MSO neurons.

Local collateral projections from the medial superior olive to the superior paraolivary nucleus in the gerbil

Local collateral projections from the medial superior olivary nucleus in the gerbil auditory brainstem were examined to study the possible communication of this nucleus with periolivary cell groups. The projections were investigated using intracellular and extracellular labeling with Biocytin in the medial superior olive (MSO) in brainstem tissue slices. Collateral axons were found to branch from the main axons of the central cells of the MSO as the latter passed through a dorsally neighboring periolivary nucleus, the superior paraolivary nucleus (SPN), toward the ipsilateral inferior colliculus (IC), their traditionally accepted target. Bouton-like endings and en passant varicosities of these collaterals appeared to contact the somata and proximal dendrites of cells within the SPN. Furthermore, close observation revealed that these collaterals terminate on at least two types of SPN cells. Intracellular labeling of the collateral axons of the MSO neurons combined with retrograde prelabeling of their target cells, however, revealed that the collaterals selectively contact the cells of the SPN that project to the ipsilateral IC. A link between the MSO and SPN has not been reported previously. This connection is of interest since SPN cells themselves project either to the cochlear nuclei (CN) or the IC. The MSO–SPN projection identified here raises the possibility that the latter may serve as an ancillary channel to convey MSO information to the IC.

Sensitivity to Interaural Time Differences in the Medial Superior Olive of a Small Mammal, the Mexican Free-Tailed Bat

Neurons in the medial superior olive (MSO) are thought to encode interaural time differences (ITDs), the main binaural cues used for localizing low-frequency sounds in the horizontal plane. The underlying mechanism is supposed to rely on a coincidence of excitatory inputs from the two ears that are phase-locked to either the stimulus frequency or the stimulus envelope. Extracellular recordings from MSO neurons in several mammals conform with this theory. However, there are two aspects that remain puzzling. The first concerns the role of the MSO in small mammals that have relatively poor low-frequency hearing and whose heads generate only very small ITDs. The second puzzling aspect of the scenario concerns the role of the prominent binaural inhibitory inputs to MSO neurons. We examined these two unresolved issues by recording from MSO cells in the Mexican free-tailed bat. Using sinusoidally amplitude-modulated tones, we found that the ITD sensitivities of many MSO cells in the bat were remarkably similar to those reported for larger mammals. Our data also indicate an important role for inhibition in sharpening ITD sensitivity and increasing the dynamic range of ITD functions. A simple model of ITD coding based on the timing of multiple inputs is proposed. Additionally, our data suggest that ITD coding is a by-product of a neuronal circuit that processes the temporal structure of sounds. Because of the free-tailed bat's small head size, ITD coding is most likely not the major function of the MSO in this small mammal and probably other small mammals.

Medial superior olive in the free-tailed bat: response to pure tones and amplitude-modulated tones.

In mammals with good low-frequency hearing and a moderate to large interear distance, neurons in the medial superior olive (MSO) are sensitive to interaural time differences (ITDs). Most small mammals, however, do not hear low frequencies and do not experience significant ITDs, suggesting that their MSOs participate in functions other than ITD coding. In one bat species, the mustached bat, the MSO is a functionally monaural nucleus, acting as a low-pass filter for the rate of sinusoidally amplitude-modulated (SAM) stimuli. We investigated whether the more typical binaural MSO of the MExican free-tailed bat also acts as an SAM filter. We recorded from 60 MSO neurons with their best frequencies covering the entire audiogram of this bat. The majority revealed bilateral excitation and indirect evidence for inhibition (EI/EI; 55%). The remaining neurons exhibited reduced inputs, mostly lacking ipsilateral inputs (28% I/EI; 12% O/EI; 5% EI/O). Most neurons (64%) responded with a phasic discharge to pure tones; the remaining neurons exhibited an additional sustained component. For stimulation with pure tones, two thirds of the cells exhibited monotonic rate-level functions for ipsilateral, contralateral, or binaural stimulation. In contrast, nearly all neurons exhibited nonmonotonic rate-level functions when tested with SAM stimuli. Eighty-eight percent of the neurons responded with a phase-locked discharge to SAM stimuli at low modulation rates and exhibited low-pass filter characteristics in the modulation transfer function (MTF) for ipsilateral, contralateral, and binaural stimulation. The MTF for ipsilateral stimulation usually did not match that for contralateral stimulation. Introducing interaural intensity differences (IIDs) changed the MTF in unpredictable ways. We also found that responses to SAMs depended on the carrier frequency. In some neurons we measured the time course of the ipsilaterally and contralaterally evoked inhibition by presenting brief frequency-modulated sweeps at different ITDs. The duration and timing of inhibition could be related to the SAM cutoff for binaural stimulation. We conclude that the response of the MSO in the free-tailed bat is created by a complex interaction of inhibition and excitation. The different time constants of inputs create a low-pass filter for SAM stimuli. However, the MSO output is an integrated response to the temporal structure of a stimulus as well as its azimuthal position, i.e., IIDs. There are no in vivo results concerning filter characteristics in a "classical" MSO, but our data confirm an earlier speculation about this interdependence based on data accessed from a gerbil brain slice preparation.

Postnatal development of the projection from the medial superior olive to the inferior colliculus in the rat

Normal projection development from the medial superior olive (MSO) to the inferior colliculus (IC) was examined by injecting Fluoro-Gold (FG), a retrograde tracer, into the IC unilaterally at postnatal days 0 (P0), P3, P7 and maturity. The rats were killed 1 day after FG injection. At all ages, labeled neurons in the MSO appeared on the ipsilateral side only, as in adult controls. The total number of MSO neurons counted in Nissl-stained sections was constant throughout the postnatal periods. The labeled frequency index of MSO neurons was increased stepwise (from 35% to 90%) with increasing postnatal stages (from P0 to adulthood), suggesting differential growth of early- and late-developing axons.