Biomedical subjects

W H A M Mulders

Publications and source records attributed to W H A M Mulders.

9 recordsLinked to original sources

PubMed2006

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.

Acoustic Stimulation↗

PubMed2005

Catecholaminergic innervation of guinea pig superior olivary complex.

In mammals, olivocochlear neurons in the superior olivary complex project to the cochlea, providing input to outer hair cells and auditory afferents contacting inner hair cells. In the rat it has been demonstrated that olivocochlear neurons receive noradrenergic input, arising from the locus coeruleus and it has been demonstrated in this species using in vitro brain slices that noradrenaline exerts a direct, mostly excitatory effect on an olivocochlear subpopulation. The guinea pig is a more commonly used animal in auditory physiology than the rat and anatomical data on noradrenaline in the auditory brainstem in this species are lacking. Because it has been shown that a compact locus coeruleus is not present in the guinea pig, subtle species differences might be expected. Therefore, using immunohistochemical and tracing techniques we have investigated in the guinea pig (1) the noradrenergic and dopaminergic innervation of the superior olivary complex, (2) the anatomical relationship between noradrenergic fibres and olivocochlear neurons and (3) the origin of the noradrenergic input to this brainstem region. The results show that the guinea pig superior olivary complex receives moderately dense noradrenergic innervation and no dopaminergic innervation. In addition, noradrenergic fibres and varicosities were observed in close contact with both somata and dendrites of olivocochlear neurons, strongly suggestive of synaptic contacts. Finally the results show that a significant component of the noradrenergic innervation of the guinea pig superior olivary complex arises in the locus subcoeruleus, which is a structure likely to be the homologue of the locus coeruleus in rats and other species.

Animals↗

PubMed2005

Noradrenergic modulation of brainstem nuclei alters cochlear neural output.

The peripheral auditory sense organ, the cochlea, receives innervation from lateral and medial olivocochlear neurons in the brainstem. These neurons are able to modulate cochlear neural output. Anatomical studies have shown that one of the neurotransmitters which is present in varicosities surrounding the olivocochlear neurons in the brainstem is noradrenaline and previous work on brainstem slices has demonstrated a generally excitatory effect of noradrenaline on medial olivocochlear neurons. In order to assess in vivo the function of the noradrenergic inputs to olivocochlear neurons, we injected noradrenaline in the brainstem of anaesthetised guinea pigs and recorded ipsilateral cochlear electrical activity. Injections of noradrenaline close to the lateral olivocochlear neurons evoked increases in the sound-driven neural activity from the cochlea, measured as compound action potential (CAP) amplitude, as well as in the spontaneous activity, measured as amplitude of the 900 Hz peak of the spectrum of the neural noise in the cochlear fluids. In contrast, noradrenaline in the vicinity of the medial olivocochlear neurons evoked inhibitory effects on both the CAP amplitude and 900 Hz peak. These results indicate most likely an excitatory action of noradrenaline on both the lateral and medial olivocochlear neurons in the brainstem, and show that such noradrenergic inputs can modulate cochlear function.

Action Potentials↗

PubMed2004

Diverse responses of single auditory afferent fibres to electrical stimulation of the inferior colliculus in guinea-pig.

Medial olivocochlear (MOC) neurons in the auditory brainstem project to the cochlea and inhibit cochlear neural output by their action on the cochlear outer hair cells. The function of the lateral olivocochlear (LOC) neurons, projecting to the auditory primary afferents is still under debate. Recent studies have suggested that the olivocochlear system can have frequency-specific, spatially restricted effects within the cochlea. It has been shown that the inferior colliculus (IC) projects to the MOC neurons in a tonotopic manner and that electrical stimulation of the IC can activate the MOC system, suppressing cochlear gross potentials. In addition, it has been shown that stimulation of the IC may be able to activate the LOC neurons. We investigated the effect of IC stimulation on single units in the cochlea of guinea-pigs and searched for evidence of spatially restricted effects of the MOC system and effects of the LOC system. We found a variety of effects on single units. About 40% of units were unchanged whereas others (53%) showed inhibitory effects, reflected in a rightward shift of their rate-level function, sometimes accompanied by a suppression of the spontaneous rate. About 18% of the inhibited neurons showed an increased spontaneous rate. In 5% of the units we observed an excitatory effect of IC stimulation, resulting in a leftward shift of the rate-level functions. We also found that the effect could vary greatly between units of the same and adjacent frequencies within a single animal. These results imply an involvement of another regulatory system besides the MOC system, possibly the LOC system, which acts directly on the primary afferents. These data also demonstrate that the olivocochlear system is capable of eliciting highly localized effects on different frequency regions in the cochlea.

Acoustic Stimulation↗

PubMed2004

Dopaminergic olivocochlear neurons originate in the high frequency region of the lateral superior olive of guinea pigs.

Dopaminergic neurons are known to exist within the lateral superior olive (LSO). The LSO is the nucleus of origin of the lateral olivocochlear neurons, which project to the cochlea and synapse onto the primary afferents contacting the inner hair cells. We investigated whether the dopaminergic neurons in the LSO are part of the lateral olivocochlear neuron population. We combined intracochlear injections of a fluorescent retrograde tracer with immunofluorescent staining of tyrosine hydroxylase (TH). TH was used as a marker for dopaminergic neurons. After the injection with retrograde tracer most of the TH-labelled neurons in the LSO also contained the tracer, which directly demonstrates for the first time that the TH-labelled, dopaminergic neurons in the LSO are lateral olivocochlear neurons. TH-labelled neurons were not equally distributed over the LSO as is observed for the lateral olivocochlear neurons in general. TH-labelled neurons were almost exclusively seen in the medial, high frequency, limb of the LSO. Since the projection of the lateral olivocochlear neurons to the cochlea is known to be tonotopic, we investigated the TH-labelling in the cochlea as well. We found that the staining pattern of TH in the cochlea is in broad agreement with the distribution of TH-labelling in the LSO. Cochlear sections showed dense labelling in the basal and second, high frequency, turns and decreasing intensity of staining in the third turn, while the extreme apical, low frequency, turn was almost devoid of any positive TH-labelling. These observations imply that the dopaminergic neurons of the lateral olivocochlear system may play a role in the selective suppression of the high frequency fibers of the auditory system.

Animals↗

PubMed2003

Olivocochlear collaterals evoke excitatory effects in onset neurones of the rat cochlear nucleus.

Axons of medial olivocochlear neurones in the superior olivary complex terminate on the outer hair cells of the cochlea and also give off collaterals that terminate in the cochlear nucleus. Previous work in our laboratory, using extracellular recordings in the cochlear nucleus, has indicated that stimulation of the olivocochlear axons may have an excitatory effect on specific cell populations of the cochlear nucleus, such as onset-choppers, in contrast to the peripheral suppressive action of the same axons. We have investigated whether this excitation is produced by action of the olivocochlear collaterals in the cochlear nucleus or whether it is mediated via the peripheral suppression, by measuring intracellular responses in the rat cochlear nucleus to electrical stimulation of the olivocochlear axons in silence. The results demonstrate that single shocks applied to the olivocochlear axons can evoke excitatory postsynaptic potentials in onset neurones. We observed an inhibitory effect in one chopper only. In the same animals in all other neurones investigated (i.e. three primary-like neurones and eight choppers) the same stimulation was without any effect on cell membrane potential. We conclude that the excitatory effects in onset neurones are not caused by suppression in the auditory peripheral organ, but by activation of olivocochlear collaterals in the cochlear nucleus.

Animals↗

PubMed2002

Learning deficits in aged rats related to decrease in extracellular volume and loss of diffusion anisotropy in hippocampus.

The extracellular space (ECS) is the microenvironment of the nerve cells and an important communication channel, allowing for long-distance extrasynaptic communication between cells. Changes in ECS size, geometry, and composition have been reported in diverse (patho)physiological states, including aging. In the present study, real-time tetramethylammonium (TMA+) iontophoresis was used to quantify ECS diffusion parameters in different brain regions of adult and behaviorally characterized aged rats. Prior to ECS diffusion measurement, superior and inferior learners were selected from a large group of aged rats, according to their performance in the open-field water maze. The main finding was that the degree of impaired maze performance of old rats correlates, firstly, with decrease in ECS volume, loss of diffusion anisotropy in hippocampus, and degree of astrogliosis, and secondly, with disorganization of the astrocytic processes and reduction of hippocampal ECS matrix molecules. Importantly, no significant differences were found in the density of neurons in any region of the hippocampus or dentate gyrus. The alterations in hippocampal diffusion parameters evident in aged animals with severe learning deficits could account for the learning impairment, due to their effects on extrasynaptic volume transmission and/or on the "cross-talk" between synapses, which has been suggested to be involved in neural processes associated with learning and memory formation.

Aging↗

PubMed2002

Inputs from the cochlea and the inferior colliculus converge on olivocochlear neurones.

Medial olivocochlear (MOC) neurones, located in the superior olivary complex, can suppress cochlear gain by their action on the cochlear outer hair cells. Inputs from the contralateral cochlea and the inferior colliculus (IC) have been separately shown to increase activity of MOC neurones. In this study we have investigated in guinea-pigs under barbiturate anaesthesia the interactions between these two inputs by combining electrical stimulation of the IC with acoustic stimulation of the contralateral cochlea. Electrical stimulation of the IC resulted in a significant suppression of the amplitude of the compound action potential (CAP) of the auditory nerve to test tones. This suppression was equivalent to an average decrease in sound intensity of 5.7 dB and 3.7 dB for contralateral and ipsilateral stimulation, respectively. Acoustic stimulation of the contralateral cochlea with broadband noise produced no detectable change in the amplitude of the CAP in the test cochlea in all but one animal. However, simultaneous electrical stimulation of the IC and acoustic stimulation of the contralateral cochlea resulted in a reduction in CAP amplitude that was markedly larger than that produced by IC stimulation alone. The suppression with the addition of contralateral noise was equivalent to a mean reduction in sound intensity of 8.7 dB with contralateral and 5.7 dB with ipsilateral IC stimulation. We hypothesise that excitatory input from the contralateral cochlea converges with excitatory input from the IC on the MOC neurones and in this way augments the activity of these neurones, resulting in a larger peripheral effect.

Acoustic Stimulation↗

PubMed2002

Dual action of olivocochlear collaterals in the guinea pig cochlear nucleus.

Axons of olivocochlear neurones in the superior olivary complex terminate on hair cells of the cochlea, reducing the sensitivity to sound. These axons also have collateral branches to neurones in the cochlear nucleus, the first processing centre in the brainstem. Anatomical data show that these collaterals terminate mainly in the granule cell area but their precise neuronal targets and the effects they might have are unknown. We have studied the effects of these collaterals in guinea pigs, by electrically stimulating the olivocochlear axons at the floor of the IVth ventricle while recording single neurone responses in the cochlear nucleus. We eliminated the peripheral effects of olivocochlear stimulation either by destruction of the target receptor cells using chronic administration of kanamycin, or by acute perfusion of the cochlea with strychnine, a specific blocker of the postsynaptic receptors. Electrical stimulation of the olivocochlear axons in normal animals caused a variety of effects on cochlear nucleus neurones. In some neurones, there was suppression of spontaneous firing and a reduction in sensitivity to sound, while in others there was an excitatory effect of olivocochlear axon stimulation. When the peripheral olivocochlear action was eliminated, we still found both inhibition and excitation in the cochlear nucleus. These results show that the effects of olivocochlear stimulation on cochlear nucleus responses are not a simple passive reflection of peripheral changes but are a result of complex interactions between peripheral suppression of afferent input and collateral-mediated excitation and possibly also inhibition.

Action Potentials↗