Gentamicin abolishes all cochlear effects of electrical stimulation of the inferior colliculus

Electrical stimulation of the inferior colliculus (IC) has been shown to result in suppression of cochlear output, due to activation of the medial olivocochlear system. This auditory efferent system originates in the brainstem and terminates on the outer hair cells in the cochlea. Recently, excitatory effects of IC stimulation have also been reported, both on cochlear gross potentials and on primary auditory afferents. It has been hypothesized that this excitation is due to co-activation of the lateral olivocochlear system, which synapses on the primary auditory afferent fibres contacting the inner hair cells. If stimulation of the IC leads to the activation of both the medial and lateral olivocochlear system, resulting in a mixture of inhibitory and excitatory effects in the cochlea, then removal of the inhibitory effects, by blocking the medial system, should lead to more pronounced excitatory effects out in the periphery. To investigate this hypothesis, we recorded the effect of IC stimulation on cochlear gross potentials as well as on single auditory primary afferents in guinea pigs following block of the medial olivocochlear system with gentamicin. We found that administration of gentamicin, whether intraperitoneally or by intracochlear perfusion, blocked all effects of IC stimulation, whether inhibitory or excitatory. These data strongly suggest that all effects observed after IC stimulation, both inhibitory as well as excitatory, are due to the activation of the medial olivocochlear system.     

Physiology of pathway from dorsal cochlear nucleus to inferior colliculus revealed by electrical and auditory stimulation

Summary The dorsal cochlear nucleus (DCN) projects axons to the contralateral central nucleus of the inferior colliculus (ICC) via the dorsal acoustic stria (DAS). In the anaesthetised cat, when brief electrical stimuli are applied to the caudal surface of DCN, single unit and field activity is evoked preferentially in the ventro-lateral region of ICC. Most single ICC units judged by electrical stimulation to have received a direct input from DCN are excited by contralateral tonal stimulation and inhibited or uninfluenced by ipsilateral tones. The sharp non-monotonic intensity functions of most of these units are similar to those of units in the dorsal cochlear nucleus, but ipsilateral inhibition is likely to be provided by a source other than DCN. Thus, although it is suggested that axons of DAS terminate preferentially in the ventro-lateral aspect of the contralateral ICC, it is likely that at least some neurones in this latter region receive additional input from another source — possibly the lateral superior olivary nucleus.This study was supported by grants from the Australian Research Grants Committee     

Response of inferior colliculus neurons to electrical stimulation of the auditory nerve in neonatally deafened cats.

Response properties of neurons in the inferior colliculus (IC) were examined in control and profoundly deafened animals to electrical stimulation of the auditory nerve. Seven adult cats were used: two controls; four neonatally deafened (2 bilaterally, 2 unilaterally); and one long-term bilaterally deaf cat. All control cochleae were deafened immediately before recording to avoid electrophonic activation of hair cells. Histological analysis of neonatally deafened cochleae showed no evidence of hair cells and a moderate to severe spiral ganglion cell loss, whereas the long-term deaf animal had only 1-2% ganglion cell survival. Under barbiturate anesthesia, scala tympani electrodes were implanted bilaterally and the auditory nerve electrically stimulated using 100 micros/phase biphasic current pulses. Single-unit (n = 419) recordings were made through the lateral (LN) and central (ICC) nuclei of the IC; responses could be elicited readily in all animals. Approximately 80% of cells responded to contralateral stimulation, whereas nearly 75% showed an excitatory response to ipsilateral stimulation. Most units showed a monotonic increase in spike probability and reduction in latency and jitter with increasing current. Nonmonotonic activity was seen in 15% of units regardless of hearing status. Neurons in the LN exhibited longer latencies (10-25 ms) compared with those in the ICC (5-8 ms). There was a deafness-induced increase in latency, jitter, and dynamic range; the extent of these changes was related to duration of deafness. The ICC maintained a rudimentary cochleotopic organization in all neonatally deafened animals, suggesting that this organization is laid down during development in the absence of normal afferent input. Temporal resolution of IC neurons was reduced significantly in neonatal bilaterally deafened animals compared with acutely deafened controls, whereas neonatal unilaterally deafened animals showed no reduction. It would appear that monaural afferent input is sufficient to maintain normal levels of temporal resolution in auditory midbrain neurons. These experiments have shown that many of the basic response properties are similar across animals with a wide range of auditory experience. However, important differences were identified, including increased response latencies and temporal jitter, and reduced levels of temporal resolution.     

Effects of stimulation of the primary auditory cortex upon colliculogeniculate neurons in the inferior colliculus of the cat

Electrical stimulation of the primary auditory cortex (AI) of the cat was found to evoke EPSPs, IPSPs or EPSP-IPSP sequences in colliculogeniculate (CG) neurons in the inferior colliculus (IC) which responded antidromically to stimulation of the medial geniculate nucleus. The CG neurons responding to the AI stimulation with short-latency EPSPs (1.0-1.4 msec) were located in the dorsomedial portion of the central nucleus of the IC. On the other hand, latencies of IPSPs elicited in CG neurons by AI stimulation ranged from 2.0 to 4.5 msec.     

Intracellular recording reveals temporal integration in inferior colliculus neurons of awake bats

The central nucleus of the inferior colliculus (IC) is a major integrative center in the central auditory system. It receives information from both the ascending and descending auditory pathways. To determine how single IC neurons integrate information over a wide range of sound frequencies and sound levels, we examined their intracellular responses to frequency-modulated (FM) sounds in awake little brown bats (Myotis lucifugus). Postsynaptic potentials were recorded in response to downward FM sweeps of the range typical for little brown bats (80-20 kHz) and to three FM subcomponents (80-60, 60-40, and 40-20 kHz). The majority of recorded neurons responded to the 80- to 20-kHz downward FM sweep with a complex response. In this response an initial hyperpolarization was followed by depolarization with or without spike followed by hyperpolarization. Intracellular recordings in response to three FM subcomponents revealed that these neurons receive excitatory and inhibitory inputs from a wide range of sound frequencies. One third of IC neurons performed nearly linear temporal summation across a wide range of sound frequencies, whereas two thirds of IC neurons exhibited nonlinear summation with different degrees of nonlinearity. Some IC neurons showed different latencies of postsynaptic potentials in response to different FM subcomponents. Often responses to the later FM subcomponent occurred before responses to the earlier ones. This phenomenon may be responsible for response selectivity of IC neurons to FM sweeps.     

Modulation of cochlear afferent response by the lateral olivocochlear system: activation via electrical stimulation of the inferior colliculus

The olivocochlear (OC) efferent innervation of the mammalian inner ear consists of two subdivisions, medial (MOC) and lateral (LOC), with different peripheral terminations on outer hair cells and cochlear afferent terminals, respectively. The cochlear effects of electrically activating MOC efferents are well known, i.e., response suppression effected by reducing outer hair cells' contribution to cochlear amplification. LOC peripheral effects are unknown, because their unmyelinated axons are difficult to electrically stimulate. Here, stimulating electrodes are placed in the inferior colliculus (IC) to indirectly activate the LOC system, while recording cochlear responses bilaterally from anesthetized guinea pigs. Shocks at some IC sites produced novel cochlear effects attributable to activation of the LOC system: long-lasting (5-20 min) enhancement or suppression of cochlear neural responses (compound action potentials and round window noise), without changes in cochlear responses dominated by outer hair cells (otoacoustic emissions and cochlear microphonics). These novel effects also differed from classic MOC effects in their lack of dependence on the level and frequency of the acoustic stimulus. These effects disappeared on sectioning the entire OC bundle, but not after selective lesioning of the MOC tracts or the cochlea's autonomic innervation. We conclude that the LOC pathway comprises two functional subdivisions, capable of inducing slow increases or decreases in response magnitudes in the auditory nerve. Such a system may be useful in maintaining accurate binaural comparisons necessary for sound localization in the face of slow changes in interaural sensitivity.     

Temporal dynamics of acoustic stimuli enhance amplitude tuning of inferior colliculus neurons

Sounds in real-world situations seldom occur in isolation. In spite of this, most studies in the auditory system have employed sounds that serve to isolate physiological responses, namely, at low rates of stimulation. It is unclear, however, whether the basic response properties of a neuron derived thereof, such as its amplitude and frequency selectivities, are applicable to real-world situations where sounds occur in rapid succession. In the present study, we investigated one of the basic response properties of neurons in the bat inferior colliculus (IC), i.e., the rate-level function, to tone pulses in three different configurations: individual tone pulses of constant amplitude at different rates of stimulation, random-amplitude pulse trains, and dynamic-amplitude-modulated pulse trains the temporal pattern of which was similar to what bats encounter in a behavioral context. We reported that for the majority of IC neurons, amplitude selectivity to tone pulses was dependent on the rate of stimulation. In general, the selectivity was greater at high rates or in a behavioral context than at low rates. For a small population of IC neurons, however, the rate of stimulation had little or no effect on their rate-level functions. Thus for IC neurons, responses to sounds presented at low rates may or may not be used to predict the responses to the same stimuli presented at high rates or in a behavioral context. The possible neural mechanisms underlying the rate-dependent effects are discussed.     

Responses of inferior colliculus neurons to amplitude-modulated intracochlear electrical pulses in deaf cats

Current cochlear prostheses use amplitude-modulated pulse trains to encode acoustic signals. In this study we examined the responses of inferior colliculus (IC) neurons to sinusoidal amplitude-modulated pulses and compared the maximum unmodulated pulse rate (Fmax) to which they responded with the maximum modulation frequency (maxFm) that they followed. Consistent with previous results, responses to unmodulated pulses were all low-pass functions of pulse rate. Mean Fmax to unmodulated pulses was 104 pulses per second (pps) and modal Fmax was 60 pps. Above Fmax IC neurons ceased responding except for an onset burst at the beginning of the stimulus. However, IC neurons responded to much higher pulse rates when these pulses were amplitude modulated; 74% were relatively insensitive to carrier rate and responded to all modulated carriers including those exceeding 600 pps. In contrast, the responses of these neurons (70%) were low-pass functions of modulation frequency, and the remaining (30%) had band-pass functions with a maxFm of 42 and 34 Hz, respectively. Thus temporal resolution of IC neurons for modulated frequencies is significantly lower than that for unmodulated pulses. These two measures of temporal resolution (Fmax and maxFm) were uncorrelated (r(2) = 0.101). Several parameters influenced the amplitude and temporal structure of modulation responses including modulation depth, overall intensity and modulation-to-carrier rate ratio. We observed distortions in unit responses to amplitude-modulated signals when this ratio was 1/4 to 1/6. Since most current cochlear implant speech processors permit ratios that are significantly greater than this, severe distortion and signal degradation may occur frequently in these devices.     

The fixation area of the cat superior colliculus: effects of electrical stimulation and direct connection with brainstem omnipause neurons

The superior colliculus has long been recognized as an important structure in the generation of saccadic displacements of the visual axis. Neurons with presaccadic activity encoding saccade vectors are topographically organized and form a motor map. Recently, neurons with fixation-related activity have been recorded at the collicular rostral pole, at the area centralis representation or fixation area. Another collicular function which deals with the maintenance of fixation behavior by means of active inhibition of orientation commands was then suggested. We tested that hypothesis as it relates to the suppression of gaze saccades (gaze = eye in space = eye in head + head in space) in the head-free cat by increasing the activity of the fixation cells at the rostral pole with electrical microstimulation. Long stimulation trains applied before gaze saccades delayed their initiation. Short stimuli, delivered during the gaze saccades, transiently interrupted both eye and head components. These results provide further support for a role in fixation behavior for collicular fixation neurons. Brainstem omnipause neurons also exhibit fixation-related activity and have been shown to receive a direct excitatory input from the superior colliculus. To determine whether the collicular projection to omnipause neurons arises from the fixation area, the deep layers of the superior colliculus were electrically stimulated either at the rostral pole including the fixation area or in more caudal regions where stimulation evokes orienting responses. Forty-nine neurons were examined in three cats. 61% of the neurons were found to be orthodromically excited by single-pulse stimulation of the rostral pole, whereas only 29% responded to caudal stimulation. In addition, stimuli delivered to the rostral pole activated, on average, omnipause neurons at shorter latencies and with lower currents than those applied in caudal regions. These results suggest that excitatory inputs to omnipause neurons from the superior colliculus are principally provided by the fixation area, via which the superior colliculus could play a role in suppression of gaze shifts.