An investigation of dendritic delay in octopus cells of the mammalian cochlear nucleus

Octopus cells, located in the mammalian auditory brainstem, receive their excitatory synaptic input exclusively from auditory nerve fibers (ANFs). They respond with accurately timed spikes but are broadly tuned for sound frequency. Since the representation of information in the auditory nerve is well understood, it is possible to pose a number of questions about the relationship between the intrinsic electrophysiology, dendritic morphology, synaptic connectivity, and the ultimate functional role of octopus cells in the brainstem. This study employed a multi-compartmental Hodgkin-Huxley model to determine whether dendritic delay in octopus cells improves synaptic input coincidence detection in octopus cells by compensating for the cochlear traveling wave delay. The propagation time of post-synaptic potentials from synapse to soma was investigated. We found that the total dendritic delay was approximately 0.275 ms. It was observed that low-threshold potassium channels in the dendrites reduce the amplitude dependence of the dendritic delay of post-synaptic potentials. As our hypothesis predicted, the model was most sensitive to acoustic onset events, such as the glottal pulses in speech when the synaptic inputs were arranged such that the model's dendritic delay compensated for the cochlear traveling wave delay across the ANFs. The range of sound frequency input from ANFs was also investigated. The results suggested that input to octopus cells is dominated by high frequency ANFs

Neural Models of Subcortical Auditory Processing

An important feature of the auditory system is its ability to distinguish many simultaneous sound sources. The primary goal of this work was to understand how a robust, preattentive analysis of the auditory scene is accomplished by the subcortical auditory system. Reasonably accurate modelling of the morphology and organisation of the relevant auditory nuclei, was seen as being of great importance. The formulation of plausible models and their subsequent simulation was found to be invaluable in elucidating biological processes and in highlighting areas of uncertainty. In the thesis, a review of important aspects of mammalian auditory processing is presented and used as a basis for the subsequent modelling work. For each aspect of auditory processing modelled, psychophysical results are described and existing models reviewed, before the models used here are described and simulated. Auditory processes which are modelled include the peripheral system, and the production of tonotopic maps of the spectral content of complex acoustic stimuli, and of modulation frequency or periodicity. A model of the formation of sequential associations between successive sounds is described, and the model is shown to be capable of emulating a wide range of psychophysical behaviour. The grouping of related spectral components and the development of pitch perception is also investigated. Finally a critical assessment of the work and ideas for future developments are presented. The principal contributions of this work are the further development of a model for pitch perception and the development of a novel architecture for the sequential association of those groups. In the process of developing these ideas, further insights into subcortical auditory processing were gained, and explanations for a number of puzzling psychophysical characteristics suggested.Royal Naval Engineering College, Manadon, Plymout

Anatomical and physiological properties of the superior paraolivary nucleus in the rat

The superior paraolivary nucleus (SPON) is a group of neurons located within the superior olivary complex, a constellation of brainstem nuclei involved in auditory processing. The major inputs to the SPON arise from the contralateral ear and SPON axons target primarily the ipsilateral inferior colliculus. However, little is known regarding the neurochemical phenotypes present in the SPON and how these neurons respond to auditory stimuli. Understanding the neurochemical and physiological properties of the constituent neurons will provide insight into the functional role of the SPON and will contribute to our understanding of the neural circuitry involved in hearing. Immunocytochemical, stereological, physiological and pharmacological techniques were used to characterize SPON neurons in the rat. The presence of inhibitory neurotransmitters was investigated with immunocytochemistry and provides evidence that the SPON contains a morphologically homogeneous population of GABAergic neurons and further that these neurons receive a robust inhibitory innervation in the form of glycinergic and GABAergic inputs. Stereological estimates of total neuron number in eighteen subcortical auditory nuclei provide evidence that the SPON is a prominent brainstem cell group and a major source of ascending inhibition to the inferior colliculus. Extracellular in vivo recordings provide evidence that nearly all SPON neurons respond to sound played in the contralateral ear with spike activity timed to the stimulus offset and phase lock to amplitude modulations in complex sounds. Pharmacologically blocking glycinergic input abolished the offset response (indicating that offset activity is a rebound from glycinergic inhibition); blockade of glycinergic and GABAergic input simultaneously, resulted in broader receptive fields and reduced phase locking capabilities. Taken together, these data indicate the rat SPON is a prominent auditory cell group that provides GABAergic inhibition to the ipsilateral inferior colliculus indicating the sound offset. GABAergic inhibition has been implicated in numerous aspects of auditory physiology, including sound localization and sensitivity to stimulus duration. Therefore, the SPON plays an important role in auditory processing and offset inhibition may be involved in processing complex sounds and in creating sensitivity to stimulus duration, both important features of animal and human communication

Cellular specializations for sound localization

One of the key elements in auditory perception is the localization of sounds in space. The major cues used for localizing sounds in the azimuthal plane have long been recognized as interaural differences in time of arrival of a sound and amplitude differences between the two ears (Rayleigh 1907; Thompson 1878). High frequency sounds are reflected by the head and thereby produce interaural level differences (ILDs) that are used for localization. The head does not reflect low frequency sounds and so interaural timing differences (ITDs) are used. One of the cell groups of the auditory brainstem, the medial superior olive (MSO), functions in sound localization by comparing ITDs between the two ears. The MSO is defined as a binaural group of cells because it integrates input from the cochlear nucleus (CN) from each ear. Afferent nerve fibers from the ipsilateral CN are restricted to dendrites oriented laterally and inputs from the contralateral CN are segregated to medially oriented dendrites (Stotler 1953). At low to moderate sound levels, activation from each cochlear nucleus is below action potential threshold and MSO neurons only generate action potentials when inputs from both sides arrive within a short temporal window called the coincidence detection window.;Several cellular specializations exist along the auditory pathway that aid MSO cells in their ability to detect changes in ITD. These specializations include large nerve terminals and distinct organelle complexes located within terminals, which facilitate fast, well-timed inhibitory inputs to MSO cells. Very little is known about the role of inhibition in sound localization and proper understanding of its role depends on knowledge of the cells that impinge on the MSO and the pharmacology and kinetics of synaptic transmission in MSO cells. Also, the membranes of MSO cells contain specific voltage-gated potassium channels (Kv), these channels are known to affect membrane electrical properties, but how these channels influence ITD sensitivity is unknown. The main goal of my research was to understand these cellular specializations that contribute to neural processing of ITDs

Submillisecond monaural coincidence detection by octopus cells

In vitro and in silico studies have suggested that octopus cells in the mammalian posterior ventral cochlear nucleus (PVCN) are monaural coincidence detectors that encode the temporal structure of complex sounds. In vivo studies on these neurons, however, are rare due to several technical difficulties. We used sharp high-impedance electrodes in anesthetized gerbils to study the responses of octopus cells to click trains. We find that, even though octopus cells only fire an onset spike to pure tones, they fire in sustained fashion to trains of transients. They entrain to click trains up to 400 Hz with vector strength almost equal to one and spike jitter at similar to 100 microseconds. This temporal precision is unmatched by any other cell type in the auditory system

Encoding of Temporal Sound Features in the Rodent Superior Paraolivary Nucleus

The superior paraolivary nucleus (SPON) is a prominent cell group in the mammalian brainstem. SPON neurons are part of a monaural circuit that encodes temporal sound features in the ascending auditory pathway. Such attributes of acoustic signals are critical for speech perception in humans and likely equally as important in animal communication. While basic properties of SPON neurons have been characterized in some detail, a comprehensive examination of mechanisms that underlie their ability to precisely represent temporal information is lacking. Furthermore, little is known of how the SPON impacts its primary target, the inferior colliculus. Combinations of electrophysiological, pharmacological and histological techniques were used to investigate SPON neuronal responses to stimuli whose temporal parameters were systematically varied. In addition, properties of neurons in the inferior colliculus were examined before and after reversible inactivation of the SPON in order to explore its functional role in hearing. An after-hyperpolarization rebound mechanism was shown to generate the hallmark offset response of SPON neurons in vitro. Single-cell labeling techniques provided a detailed morphological description of cell bodies and dendrites and revealed a homogeneous population of neurons. Moreover, subthreshold ionic currents and synaptic neurotransmitter receptor systems were shown to mediate the precision of responses to temporal features of sound in vivo. It was also demonstrated that input from the SPON shapes response properties of inferior colliculus neurons to both periodic and singular temporal stimulus features. Taken together, these results suggest the SPON likely has a substantial role in temporal processing that has not been taken into account in the current understanding of the central auditory system. Demonstrating a functional role for the SPON in hearing will expand our knowledge of neuronal circuits responsible for representing biologically important sounds in both normal hearing and hearing impaired states