Conditioned enhancement and suppression in the developing auditory midbrain.

Neural responses in the adult central auditory system to binaural stimuli can be altered by preceding acoustic events, including auditory motion. To determine whether the juvenile auditory system also exhibits this feature, we have examined interaural level difference (ILD) processing in the developing gerbil. A long binaural stimulus was followed without interruption by modulation of the level difference (virtual acoustic motion), which in turn was followed smoothly by a new steady state ILD. Auditory responses of single neurons in the inferior colliculus (IC) were assessed for sensitivity to the final steady state ILD. The response of EI neurons (excited by contralateral stimulation and inhibited ipsilaterally) was examined at postnatal (P) days 17-18, P24-25, and in adult animals. In adult animals, a sudden reduction of the inhibitory stimulus level resulted in a long-lasting (median = 4.3 s) enhanced discharge rate (conditioned enhancement). In P17-18 animals, conditioned enhancement only lasted for 1.2 s. When the inhibitory stimulus level was suddenly increased, adult neurons often displayed a conditioned suppression of discharge rate (median = 4.5 s), whereas P17-18 neurons remained suppressed for a much briefer period (median = 1.2 s). Moreover, the difference between conditioned responses and control discharge rates was three-four times greater in adult neurons compared to those recorded in P17-25 animals. Because conditioned responses are sensitive to the relative balance of contralateral excitation and ipsilateral inhibition, we examined the relationship between excitatory and inhibitory thresholds. In adult animals, excitatory thresholds were an average of 12 dB lower than inhibitory thresholds, while at P17-25 excitatory and inhibitory thresholds were roughly the same. These results indicate that computational properties of juvenile and adult IC neurons differ quantitatively, and this may reflect an imbalance between excitation and inhibition. The developmental differences described herein may limit the ability of young animals to locate a sound source with the latency and accuracy of an adult.

The auditory brainstem response of aged guinea pigs.

The auditory brainstem response (ABR) technique was used to investigate potential dysfunctions in the auditory brainstem of the pigmented guinea pig (Cavia porcellus) associated with biological ageing. Animals aged from 58 days to 4 years 3 months were tested. ABRs were recorded at stimulation intensities from 85 dB HL to -10 dB HL. The auditory thresholds were found to undergo marked elevations in old animals, by an average of 32 dB. From the traces obtained, four positive deflection waves were reliably recorded. The latency of each of the four waves was evaluated at different stimulation intensities in guinea pigs of different ages. Although there was a trend for the latencies to increase in old age, these differences were not statistically significant. Similarly, there were no significant age-related changes in the inter-peak intervals. The latency/intensity functions of the four waves produced parallel curves. However, the curve from the old age group was shifted to the right, by an average of 35 dB, indicative of conductive hearing loss. There was no evidence of retro-cochlear hearing loss. Therefore, it appears that the threshold elevations in the old animals can be accounted for by conductive hearing loss, presumably in the middle ear. In 24% of the old animals tested, no ABR could be elicited. It would appear that these animals had suffered severe sensorineural hearing loss.

Neurotransmitter involvement in development and maintenance of the auditory space map in the guinea pig superior colliculus.

Neurotransmitter involvement in development and maintenance of the auditory space map in the guinea pig superior colliculus. J. Neurophysiol. 80: 2941-2953, 1998. The mammalian superior colliculus (SC) is a complex area of the midbrain in terms of anatomy, physiology, and neurochemistry. The SC bears representations of the major sensory modalites integrated with a motor output system. It is implicated with saccade generation, in behavioral responses to novel sensory stimuli and receives innervation from diverse regions of the brain using many neurotransmitter classes. Ethylene-vinyl acetate copolymer (Elvax-40W polymer) was used here to deliver chronically neurotransmitter receptor antagonists to the SC of the guinea pig to investigate the potential role played by the major neurotransmitter systems in the collicular representation of auditory space. Slices of polymer containing different drugs were implanted onto the SC of guinea pigs before the development of the SC azimuthal auditory space map, at approximately 20 days after birth (DAB). A further group of animals was exposed to aminophosphonopentanoic acid (AP5) at approximately 250 DAB. Azimuthal spatial tuning properties of deep layer multiunits of anesthetized guinea pigs were examined approximately 20 days after implantation of the Elvax polymer. Broadband noise bursts were presented to the animals under anechoic, free-field conditions. Neuronal responses were used to construct polar plots representative of the auditory spatial multiunit receptive fields (MURFs). Animals exposed to control polymer could develop a map of auditory space in the SC comparable with that seen in unimplanted normal animals. Exposure of the SC of young animals to AP5, 6-cyano-7-nitroquinoxaline-2,3-dione, or atropine, resulted in a reduction in the proportion of spatially tuned responses with an increase in the proportion of broadly tuned responses and a degradation in topographic order. Thus N-methyl--aspartate (NMDA) and non-NMDA glutamate receptors and muscarinic acetylcholine receptors appear to play vital roles in the development of the SC auditory space map. A group of animals exposed to AP5 beginning at approximately 250 DAB produced results very similar to those obtained in the young group exposed to AP5. Thus NMDA glutamate receptors also seem to be involved in the maintenance of the SC representation of auditory space in the adult guinea pig. Exposure of the SC of young guinea pigs to gamma-aminobutyric acid (GABA) receptor blocking agents produced some but not total disruption of the spatial tuning of auditory MURFs. Receptive fields were large compared with controls, but a significant degree of topographical organization was maintained. GABA receptors may play a role in the development of fine tuning and sharpening of auditory spatial responses in the SC but not necessarily in the generation of topographical order of the these responses.

Age-related changes in auditory spatial properties of the guinea pig superior colliculus.

The map of auditory space located in the deep layers of the guinea pig superior colliculus (SC) is a complex computational representation of the auditory azimuth surrounding the animal. The map undergoes a protracted developmental profile during the first postnatal month and remains plastic until well into adulthood. However, there are no data concerning the state of the collicular auditory space map in much older animals. Multi-unit responses to broadband noise stimuli presented around the azimuthal plane under anechoic conditions were recorded from the deep SC of guinea pigs of a variety of ages, up to 44 months. The data obtained show that the map remains stable up to the age of approximately 36 months. However, after this age, the map shows rapid deterioration and at 42 months, multi-unit responses did not show features consistent with a normal map. It appears that deficits accruing within the central auditory system with increasing age, combine to overcome the ability of the mechanisms of plasticity responsible for space map maintenance to keep pace with the changes, resulting in degraded SC spatial tuning with increasing age.

The effect of dark-rearing, strobe-rearing and acute visual cortex removal on the visual responses in the superficial superior colliculus of the guinea-pig.

Extracellular multi-unit responses to visual stimuli were recorded in the cells of the superficial layers of the superior colliculus (SC) in four groups of adult guinea-pigs: a control group, a strobe-reared group, a dark-reared group and a group with the ipsilateral visual cortex removed acutely. Single unit visual responses were also recorded in a control and a dark-reared group. When guinea-pigs were either strobe or dark-reared from birth, the number of directionally selective responses in the superficial SC decreased significantly. Acute removal of the visual cortex had no affect on the number of directionally selective cells recorded in the SC. The correlation between azimuthal visual receptive field and rostrocaudal position of the recording electrode in the SC was not significantly different from the control group following strobe, dark-rearing or acute visual cortex removal. These data imply that, during early development, visual information is necessary for directional selectivity of the visual responses in the superficial SC. However, the map of visual azimuthal space is essentially unperturbed by visual restriction (in the form of dark or strobe-rearing) or acute visual cortex removal.

The role of the external nucleus of the inferior colliculus in the construction of the superior collicular auditory space map in the guinea-pig.

In the guinea-pig two subcortical structures have been shown to contain representations of auditory space, the deep layers of the superior colliculus (SC) and the external nucleus of the inferior colliculus (ICX). The following investigation was undertaken to determine if the ICX influences the development of the SC auditory space map. A portion of the ICX was lesioned unilaterally when guinea-pigs were between 8 and 13 days old. Following a period of recovery, the SC mapping experiments commenced in the adult guinea-pig. Electrophysiological auditory responses were recorded from the deep layers of the SC to free-field azimuthal auditory stimulation. The data from the ICX lesioned animals revealed that the spatial tuning parameter values of the auditory receptive fields from the SC were significantly greater than those recorded in the normal control group of animals. The pooled data from the ICX lesioned group indicated that the peak angle of the response of the auditory receptive fields did not display normal topographic order. Furthermore, in several cases where the ICX lesion site was small, the position of the lesion could be correlated with the site of SC auditory space map disruption. These data indicate that, during early development, the presence of the ICX is essential for the normal emergence of an azimuthal map of auditory space in the deep layers of the guinea-pig SC.

Visual movement and pattern are important for the development of a map of auditory space in the guinea pig superior colliculus.

Previous data have indicated that, if guinea pigs are deprived of all visual information during a crucial period early in development (26-30 days after birth), the map of auditory space in the superior colliculus (SC) is completely disrupted. In the experiments reported here, multi-unit auditory receptive fields were recorded in the SC of two groups of anaesthetised guinea pigs that had been exposed to different forms of visual deprivation. One group was reared in a movement-free environment (strobe-reared) and the other group was reared in a pattern-free environment (their eyes covered with light-diffusing masks). Both groups experienced visual restriction during the crucial period for auditory space map development. In both experimental groups, the multi-unit auditory receptive fields were broad and all spatial tuning parameter values were significantly greater than the equivalent values from a control group of normal animals. In the pattern- and motion-deprived groups, a significant correlation existed between the rostro-caudal position of the recording electrode in the SC and the peak response angle of the receptive field, thus showing a degree of topographic organisation of the auditory receptive fields in the SC. However, the topographic order was less precise than that displayed by the control group of animals. These results indicate that, during development, both visual pattern and movement are important for the refinement of the SC auditory space map in the guinea pig.

Neural responses to free-field auditory stimulation in the superior colliculus of the wallaby (Macropus eugenii).

Auditory responses to free-field broad band stimulation from different directions were recorded from clusters of neurones in the superior colliculus (SC) of the anaesthetized tammar wallaby. The auditory responses were found approximately 2 mm beneath the first recording of visually evoked responses in the superficial layers, the vast majority being solely auditory in nature; only one recording responded to both auditory and visual stimulation. Responses to suprathreshold intensities displayed sharp spatial tuning to sound in the contralateral hemifield. Those from the rostral pole of the SC disclosed a preference for auditory stimuli in the azimuthal anterior field, whereas those in the caudal SC preferentially responded to sounds in the posterior field. A continuum of directionally tuned responses was seen along the rostrocaudal axis of the SC so that the entire azimuthal contralateral auditory hemifield was represented in the SC. Furthermore, tight spatial alignment was evident between the best position of the visual responses in the superficial layers in azimuth and the peak angle of the auditory response in the deeper layers.

Plasticity in the superior collicular auditory space map of adult guinea-pigs.

In the guinea-pig the development and maintenance of the superior collicular (SC) auditory space map requires both auditory and visual experience. This paper reports the results of experiments in which adult animals (of different ages) were dark-reared for 4 weeks to define the extent of the period of susceptibility to visual deprivation of the SC auditory map. Dark-rearing for 4 weeks from 100, 150 or 200 days after birth caused degradation of spatial tuning and topography of multi-unit auditory responses in the SC. In contrast, animals reared in the dark from 250 days after birth showed spatially tuned auditory responses similar to those seen in normal animals. These data suggest that the SC auditory space map in the adult guinea-pig remains susceptible to visual deprivation up to 200 days after birth.

Post-crucial period effects of visual experience and deprivation on the guinea-pig superior collicular map of auditory space.

There were two primary aims of this study. First, to observe if the map of auditory space in the superior colliculus (SC) of the guinea-pig could recover after periods of normal visual experience following visual deprivation during the crucial period. Second, to determine whether any degradation of the space map was observed when the animal was visually deprived for different lengths of time after the crucial period. Animals deprived of visual experience during the crucial period and then allowed normal experience did show a limited ability to construct a SC auditory space map. Whereas visual deprivation following normal auditory and visual experience during the crucial period caused a profound degradation, of both spatial tuning and topography, of auditory receptive fields in the SC. Additional data indicate that the SC auditory space map remains vulnerable to visual deprivation until at least 100 days after birth.

The effects of monocular enucleation on the representation of auditory space in the superior colliculus of the guinea-pig.

Multi-unit responses, to free-field auditory stimuli, in the superior colliculus were investigated in guinea-pigs following earlier removal of one eye. Enucleation resulted in disruption of the normal tuning parameter values and of the topographical precision of auditory responses in the SC both ipsilateral and contralateral to the enucleated eye. These data demonstrate that monocular enucleation prevents the normal development of the superior collicular auditory space map.