Auditory guidance in a smoke-filled tunnel.

As a test on auditory guidance, participants tried to find refuge and safety in a road tunnel in dense smoke with sound beacons over the escape exits. The beacons emitted a 'shhussing' noise with a 5-Hz pulse frequency. Three groups participated, 32 or 33 participants per group, the first with minimal instruction (sound not mentioned), the second with beacons instruction 'sound beacons help you to orient', and the third with full instruction 'sound beacons over the escape exits'. The percentage of participants finding an escape exit was 16, 21, and 70%, respectively. While the potential of auditory guidance is amply demonstrated, there is the possibility that improvement in the recognition of the sound could improve escape exit usage further. It is recommended to include in the sound of the beacon the speech fragment 'exit here'. This will probably eliminate the need for instruction. If, in the future, the beacons are used broadly (in buildings, on ships and planes), the recognition issue should diminish.

Hair cell loss in the aged guinea pig cochlea.

The various effects of ageing on the auditory system, collectively termed presbycusis, are being studied across a wide range of animal species, including humans. One contributing factor to presbycusis is thought to be losses of the sensory hair cells in the cochlea. In this study, hair cell counts were obtained from cochleas of pigmented guinea pigs (Cavia porcellus) at ages ranging from 11 days to 4 years 7 months, using scanning electron microscopy to visualize the organ of Corti. Representative samples of the basal, middle and apical turn of the cochlea were photographed for analysis. Hair cell loss was observed, even in young animals. However, the loss was greater in the aged animals, but was not distributed evenly throughout the length of the cochlea. No significant loss of hair cells was seen in the basal (high frequency) or middle turn of the cochlea of the aged animals. In the apical (low frequency) turn, there was a significant loss of hair cells in all rows of outer hair cells (up to around 20%), and was most severe in the third row. There was no loss of apical inner hair cells in the aged animals.

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.

GABA-induced long-term potentiation in the guinea-pig superior colliculus.

Although GABA (gamma-aminobutyric acid) is the major inhibitory neurotransmitter in the brain, intense activation of GABA receptors can cause excitation under certain conditions. In the superficial layers of the guinea-pig superior colliculus (SC) slice the excitatory action of GABA (< or = 3 mM) is dominant and sufficient to induce a robust and novel form of long-term potentiation, termed LTPG, of evoked field excitatory postsynaptic potentials (fEPSPs). This action of GABA could neither be mimicked by GABA-A nor -B agonists which were found to suppress synaptic transmission. Additionally, LTPG was not inhibited by the GABA-A receptor antagonist bicuculline while the GABA-C receptor antagonist imidazol-4-acetic acid prevented LTPG. Glutamatergic synaptic transmission was found to be required, as LTPG was partially use-dependent and did not emerge when glutamate receptors of the non-NMDA type were blocked during GABA application. Moreover, LTPG declined to baseline values in the presence of the NMDA antagonist D,L-2-amino-5-phosphonovaleric acid (APV). In addition, the L-type calcium channel blocker nifedipine inhibited the induction of LTPG. It is suggested that activation of excitatory GABA non-A, non-B receptors can lead to LTP in the SC, which may be of major importance for plastic events since the content of GABA and GABA receptors are particularly high in this brain area.

Glycine induces a novel form of long-term potentiation in the superficial layers of the superior colliculus.

1. The mammalian superior colliculus (SC) is a midbrain nucleus containing space maps of different sensory modalities which show various forms of age- and activity-dependent plasticity in vivo and in vitro. In the present study, we aimed to characterize the role of glycine (Gly) receptors in the SC, and we observed that application of glycine (Gly; 500 microM and 3 mM) for 7 min to SC slices of adult guinea-pigs caused a novel form of long-term potentiation (termed LTPgly) of evoked excitatory postsynaptic potentials recorded in the superficial layers. 2. The strength of potentiation was found to be concentration-dependent and partially independent from synaptic stimulation. 3. LTPgly did not involve NMDA receptor activation as proven by the lack of inhibition by 100 microM D,L-2-amino-5-phosphonovaleric acid (APV) and 10 microM MK-801. 4. LTPgly could only be masked but not prevented by strychnine (100 microM) and remained undisturbed in the presence of picrotoxin (100 microM). 5. Inhibition of carbonic anhydrase by acetazolamide (20 microM) had no effect on LTPgly suggesting that the excitatory action of Gly is not due to a differential breakdown of the Cl-/HCO3 gradients. 6. As indicated by the inhibition of LTPgly of the fEPSP slope by the L-type calcium channel blocker nifedipine (20 microM), voltage-dependent calcium channels are the source for Ca2+ elevation as the intracellular trigger. 7. Our data provide the first evidence for a role of Gly in SC synaptic transmission. They illustrate a so far unknown action of Gly which can lead to long-lasting changes of synaptic efficacy and which is not mediated via NMDA-related or strychnine-sensitive binding sites.

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 contribution of protein kinases to plastic events in the superior colliculus.

1. The superior colliculus (SC)/optic tectum is a multi-layered midbrain area that harbours representations of visual and auditory space and somatic body surface. The development and maintenance of these sensory maps has been shown to involve activity and experience-dependent mechanisms. 2. The implantation of an extra eye primordium into the developing forebrain of Rana pipens results in the formation of dually innervated tecta that would have normally be solely innervated by the contralateral retina. The retinal projections are arranged in an interdigitating pattern of alternate stripes of terminations from each retina. The establishment of this striped pattern requires retinal activity and depends on N-methyl-D-aspartate (NMDA) receptors. Manipulation of protein kinase activity leads to the formation of an abnormal stripe pattern. 3. Regeneration of the goldfish retinotectal projection, following crush of the optic nerve, occurs in an activity dependent manner involving NMDA receptors. Furthermore, a critical period exists, during which retinal activity is vital for reformation of the visual map. Protein kinase manipulations during this period disrupt normal reformation. The same manoeuvres at other time points have little effect on map reformation. 4. An unusual form of long-term potentiation (SC-LTP) has been demonstrated in the in vitro preparation of the guinea-pig SC. By stimulating the optic layer of the SC, a postsynaptic potentiation can be recorded in the superficial grey layer. The expression of SC-LTP is masked but not prevented by blockade of NMDA receptors. The role of protein kinases in this form of synaptic modification has also been studied using various manipulations and inhibitors with varying substrate specificity. Whereas H7, an inhibitor reputed to be protein kinase C specific, only masks the expression of SC-LTP, K252a which has a broad substrate specificity blocks the induction of SC-LTP. 5. Experience-dependent formation of the auditory space map in the deeper layers of the SC is believed to be under the instruction of the visual representation in the superficial layers. Furthermore, a crucial period exists during which normal auditory and visual experience are required for successful establishment of the auditory map. Chronic exposure to 5-aminophosphonopentanoic acid (AP5) during this time prevents the formation of the map. Chronic exposure to K252a, a broad kinase inhibitor, over the same time period, also disrupts the formation of the auditory space map. 6. Taken together, these models emphasise the role of protein kinases in synaptic plasticity observed in the SC. Furthermore, interference with protein kinase activity at crucial stages of regeneration or development appears to disrupt the sequence of events that lead to the consolidation of SC receptive fields.

Response habituation in the superficial layers of the guinea-pig superior colliculus in vitro.

Response habituation (RH) has been suggested to reflect the role of the mammalian superior colliculus (SC) as a novelty detector. In the present study, we show that RH occurs in the SC slice preparation and is caused partially by the activation of inhibitory GABA receptors. No evidence for the contribution of presynaptic transmitter release was found and the block of N-methyl-D-aspartate (NMDA) receptors facilitated RH for a higher stimulation frequency. Since RH could not be abolished completely by any treatment, it appears that other mechanisms such as a general metabolic fatigue may contribute to RH. Nevertheless, RH must be taken into account when performing repeated stimulation in the SC slice preparation.

Paired-pulse depression in the superficial layers of the guinea-pig superior colliculus.

Paired-pulse depression (PPD) and facilitation are found at many synapses in the central nervous system. In the present study, we aimed to characterise the paired-pulse behaviour of evoked postsynaptic potentials in the superficial layers of slices of the superior colliculus (SC) of adult guinea-pigs. We observed PPD for inter-stimulus intervals between 10 and 500 ms, for both high (90% of maximum) and low (30% of maximum) stimulus intensities. This depression could be converted into a facilitation when the probability of transmitter release was reduced in low Ca2+/high Mg2+ solution, but only when the low stimulus intensity was applied. Elimination of GABA(A) receptor mediated currents by bicuculline caused an enhanced general excitation and enhanced PPD. Application of the GABA(B) receptor antagonist CGP35348 reduced PPD, suggesting the contribution of slow inhibitory postsynaptic currents. The NMDA receptor antagonist D,L-amino-5-phosphonovaleric acid (APV) did not lead to major alterations of PPD. We conclude that presynaptic mechanisms affecting Ca2+-dependent glutamate release are crucial for PPD in the superficial SC. Nevertheless, postsynaptic inhibitory components and probably polysynaptic pathways also seem to contribute to PP behaviour in the SC. Moreover, PPD in the SC has a different profile compared with other brain areas. Here, PPD may be crucially involved in setting the threshold for novel vs. background stimulation, since the SC is known to trigger orienting responses towards novel sensory stimuli.

Severing the intercollicular commissure prevents bilateral disruption of the map of auditory space in the superior colliculi following monocular enucleation.

A previous study demonstrated that developmental monocular enucleation resulted in bilateral disruption of the formation of the auditory space map in both superior collculi, even though only one colliculus had been deprived of visual input. The present study found similar map disruption, when monocular enucleation was carried out following the initial emergence of the map at 32 days after birth. The study also investigated the effect of monocular enucleation plus simultaneous transection of the intercollicular commissure (a recognised pathway for communication between the colliculi). Multi-unit responses to free-field auditory stimuli were recorded from both colliculi of the two experimental groups. In the group which had later monocular enucleation alone, the auditory responses were disrupted in a manner very similar to those recorded from animals which had undergone early monocular enucleation. Similarly, in the group in which the collicular commissure had been severed at the time of monocular enucleation, the auditory responses were also disrupted in the colliculus contralateral to the enucleation. In contrast, the colliculus ipsilateral to the enucleation exhibited normal, topographically organised, auditory responses. Thus, severing the intercollicular commissure at the time of monocular enucleation protected the map of auditory space in the ipsilateral colliculus.

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.

The developmental emergence of the representation of auditory azimuth in the external nucleus of the inferior colliculus of the guinea-pig: the effects of visual and auditory deprivation.

A topographic representation of the auditory azimuth has been described in the external nucleus of the inferior colliculus (ICX) of the guinea-pig [3]. This representation is characterized by directional multi-unit responses, at threshold stimulation intensities, with directional preferences organized in such a way as to represent the auditory azimuth along the rostro-caudal axis of the ICX. The following paper considers the emergence of that map and the role of developmental experience in its elaboration. Multi-unit responses to free-field broad-band auditory stimuli were recorded in the ICX. At threshold stimulation intensities, multi-unit receptive fields (MURFs) obtained from younger animals showed the same discrete spatial tuning as found in MURFs from animals older than 35 DAB (days after birth). However, a normal adult topographic representation was not present until animals were at least 30-32 DAB. Visual deprivation, by dark-rearing from birth until mapping (at 35-43 DAB), had no obvious detrimental effects on auditory receptive field size or topographic order in the ICX. Auditory deprivation was achieved by rearing animals in an environment of continuous omnidirectional noise from birth until mapping (47-53 DAB). Following auditory deprivation, receptive fields remained relatively discrete, but no correlation between rostro-caudal position of the recording site and the angle of the best response was observed. Thus, the representation of auditory azimuth in the ICX appears to be unperturbed by developmental visual deprivation but is susceptible to developmental auditory deprivation.

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.

A topographic representation of auditory space in the external nucleus of the inferior colliculus of the guinea-pig.

The possibility that the external nucleus of the inferior colliculus (ICX) of the pigmented guinea-pig contains a map of auditory space has been investigated. Auditory stimuli consisted of broad-band sound delivered under free-field anechoic conditions from a range of positions around the animal's azimuthal axis. The responses of clusters of neurons in the ICX to threshold and to near-threshold stimuli displayed sharp spatial tuning. The responses recorded from rostral ICX revealed a preference for auditory stimuli in the anterior field while more caudal neurons preferentially responded to sounds presented in the posterior field. Neurons at intermediate points, along the rostro-caudal axis of the nucleus, displayed preferences for sound stimuli in appropriately intermediate field positions along the contralateral azimuthal axis. At higher stimulus intensities the spatial tuning of the responses decreased, but the optimal direction of preference was usually retained. The contribution of binaural processing to auditory spatial tuning was evident, since unilateral cochlea ablation destroyed the spatial tuning at higher stimulus intensities. The results presented provide the first evidence that a topographically ordered representation of the contralateral auditory azimuth is present in the ICX of a mammal.