A simulation of chopper neurons in the cochlear nucleus with wideband input from onset neurons

The unique temporal and spectral properties of chopper neurons in the cochlear nucleus cannot be fully explained by current popular models. A new model of sustained chopper neurons was therefore suggested based on the assumption that chopper neurons receive input both from onset neurons and the auditory nerve (Bahmer and Langner in Biol Cybern 95:4, 2006). As a result of the interaction of broadband input from onset neurons and narrowband input from the auditory nerve, the chopper neurons in our model are characterized by a remarkable combination of sharp frequency tuning to pure tones and faithful periodicity coding. Our simulations show that the width of the spectral integration of the onset neuron is crucial for both the precision of periodicity coding and their resolution of single components of sinusoidally amplitude-modulated sine waves. One may hypothesize, therefore, that it would be an advantage if the hearing system were able to adapt the spectral integration of onset neurons to varying stimulus conditions.     

Auditory centre projection of the lower brainstem to the dorsal cochlear nucleus in the rabbit

Afferent projection to dCN from SOC and the periolivary regions was studied in the rabbit by retrograde transport of WGA-HRP. The projection originates primarily from the bilateral TrV and TrL with a very clear contralateral and ipsilateral predominance, respectively. A clear-cut topographical relationship was disclosed between location of neurons in these nuclei and projection sites in dCN. Thus, the medial region of dCN is target of projection arising from the medial regions of TrV and TrL, whereas the lateral region of dCN is supplied by projection from their lateral regions. Although participation in the projection of the ipsilateral TrV is smaller and the contralateral TrL is very weak, the pattern of these preferential connections is also apparent. Minute connections were traced from the other principal olivary nuclei, i.e. MSO, LSO and TrM, mainly from neurons located in their peripheral regions. In the periolivary region the cells of origin of the projection were found in VLPO and VMPO, and in lesser extent in DPO, DMPO, DLPO, RPO and CPO. The present results are discussed in comparison with those of earlier studies and with reference to other inputs to CN.     

Identification of tuberculo-ventral neurons in the polymorphic layer of the rat dorsal cochlear nucleus

The tuberculo-ventral tract represents a short nervous circuit within the auditory cochlear nuclei. Tuberculo-ventral neurons of the dorsal cochlear nucleus send isofrequency inhibitory inputs to bushy cells of the ventral cochlear nucleus. Injection of wheat germ agglutinin conjugated to horseradish peroxidase into the rat ventral cochlear nucleus, labelled tuberculo-ventral neurons retrogradely in the deep polymorphic layer of the ipsilateral dorsal cochlear nucleus. Five to 20% of the perimeter of these cells was covered by synaptic boutons, most of which contained flat and pleomorphic vesicles. These boutons contained glycine and sometimes GABA. Occasional small axo-somatic boutons contained round vesicles and were immunonegative for both glycine and GABA. This study shows that the synaptic profile of tuberculo-ventral neurons is different from that of other medium-size glycinergic neurons within the polymorphic layer or more superficial regions of the dorsal cochlear nucleus like cartwheel neurons. In fact the latter mostly receive boutons that contain pleomorphic vesicles.     

Cytology of large neurons in the guinea pig dorsal cochlear nucleus contacting the inferior colliculus

Large neurons in the dorsal cochlear nucleus of the guinea pig which project to the inferior colliculus were identified after injections of the neural tracer WGA-HRP. Retrograde labelled cells (pyramidal and giant neurons) in the dorsal cochlear nucleus were glycine and GABA immunonegative and showed a similar ultrastructure. Between 30 and 60% of their perimeter was covered by axo-somatic boutons, most of which (>50%) contained pleomorphic synaptic vesicles. Other boutons (about 40% of total) contained flat vesicles and few (5-6%) contained round vesicles, a characteristic of the excitatory cells innervating the inferior colliculus. Immunogold-cytochemistry, coupled to silver intensification, showed that more than 50% of axo-somatic pleomorphic boutons and over 90% of boutons containing flat and pleomorphic vesicles store glycine. Rare WGA-HRP labelled axo-somatic boutons containing flat-pleomorphic vesicles were seen on pyramidal and giant neurons. This suggests that a few inhibitory collicular terminals contact the excitatory large neurons in the dorsal cochlear nucleus.     

Laminar ultrastructure of the dorsal cochlear nucleus in rats

The laminar ultrastructure of the dorsal cochlear nucleus was studied in ultrathin wide frontal sections, passing through all layers of the nucleus, placed on blinds with a Formvar film. The ultrastructural characteristics of cells corresponding to the cell types distinguished previously by light microscopy are described. The laminar distribution of the axon terminals was studied. In the surface and middle layers of the neuropil, by contrast with the deep layer, large branching terminals measuring 6–8 µ with spherical synaptic vesicles 40–50 nm in diameter, small terminals measuring 1–3 µ with spherical synaptic vesicles 45–60 nm in diameter, and thin unmyelinated fibers running perpendicularly to the plane of the section were predominant. On transition from the middle to the deep layer there was a corresponding increase in the number of myelinated axons and large oval-shaped terminals measuring 4–6 µ, with central mitochondria and neurofilaments, and also with spherical synaptic vesicles 50–60 nm in diameter, in the neuropil. In the surface and middle layers granular cells also were more numerous than in the deep layer. The functional significance of terminals of each type is discussed.N. A. Semashko Moscow Medical Stomatologic Institute. Translated from Neirofiziologiya, Vol. 10, No. 4, pp. 368–374, July–August, 1978.     

Computational model of response maps in the dorsal cochlear nucleus

The neurons in the mammalian (gerbil, cat) dorsal cochlear nucleus (DCN) have responses to tones and noise that have been used to classify them into unit types. These types (I–V) are based on excitatory and inhibitory responses to tones organized into plots called response maps (RMs). Type I units show purely excitatory responses, while type V units are primarily inhibited. A computational model of the neural circuitry of the mammalian DCN, based on the MacGregor neuromime, was used to investigate RMs of the principal cells (P-cells) that represent the fusiform and giant cells. In gerbils, fusiform cells have been shown to have primarily type III unit response properties; however, fusiform cells in the cat DCN are thought to have type IV unit response properties. The DCN model is based on a previous computational model of the cat (Hancock and Voigt Ann Biomed Eng 27: 73–87, 1999) and gerbil (Zheng and Voigt Ann Biomed Eng 34: 697–708, 2006) DCN. The basic model for both species is architecturally the same, and to get either type III unit RMs or type IV unit RMs, connection parameters were adjusted. Interestingly, regardless of the RM type, these units in gerbils and cats show spectral notch sensitivity and are thought to play a role in sound localization in the median plane. In this study, further parameter adjustments were made to systematically explore their effect on P-cell RMs. Significantly, type I, type III, type III-i, type IV, type IV-T and type V unit RMs can be created for the modeled P-cells. Thus major RMs observed in the cat and gerbil DCN are recreated by the model. These results suggest that RMs of individual DCN projection neurons are the result of specific assortment of excitatory and inhibitory inputs to that neuron and that subtle differences in the complement of inputs can result in different RM types. Modulation of the efficacy of certain synapses suggests that RM type may change dynamically.     

Oscillating neurons in the cochlear nucleus: I. Experimental basis of a simulation paradigm

Anatomical and physiological auditory data and pitch measurements are presented including some additional analysis. The data provide the basis for a new computer model of sustained chopper neurons in the ventral cochlear nucleus. New and old evidence indicating a preference for multiples of 0.4 ms in oscillations of chopper neurons in the cochlear nucleus of different species such as man, cats, and Guinea fowls, is summarized. Our hypothesis is that the time constant of 0.4 ms is due to the minimum synaptic delay of chopper neuron connections. Anatomical findings show that chopper neurons are indeed connected and can excite each other; a model of a circular network of neurons that are connected via synapses with a delay of 0.4 ms is thus plausible. Results concerning frequency tuning and dynamical properties of periodicity encoding of chopper neurons are reviewed. It is concluded that chopper neurons receive input both from auditory nerve fibres and onset neurons.     

The polypeptide PEP-19 is a marker for Purkinje neurons in cerebellar cortex and cartwheel neurons in the dorsal cochlear nucleus

This light and electron microscopic immunocytochemical study shows that the polypeptide PEP-19, a presumptive calcium binding protein specific to the nervous system, represents an excellent marker for cerebellar Purkinje cells and dorsal cochlear nucleus (DCoN) cartwheel cells. The polypeptide clearly reveals the entire populations of both types of neurons, including their complete dendritic and axonal arborizations. Other PEP-19 containing neurons in the two regions display weak immunoreactivity restricted to the cell body or to cell body and principal dendrites. Electron microscopic localization of PEP-19-like immunoreactivity reveals similarities between this polypeptide, parvalbumin, and a 28K vitamin D-dependent calcium binding protein. However, calmodulin, which is expressed in both Purkinje and granule cells, may differ from PEP-19. Similarities between the organization of the cerebellar cortex and the DCoN superficial layers have been known for some time, with several types of neurons in one system having their presumed homologue in the other. These data provide further support for the proposed structural and functional homology between Purkinje and cartwheel neurons, and establishes PEP-19 as a useful marker for examining degeneration of these two neuronal populations in murine cerebellar mutants.     

Modeling inhibition of type II units in the dorsal cochlear nucleus

 Type II units in the dorsal cochlear nucleus (DCN) are characterized by vigorous but nonmonotonic responses to best frequency tones as a function of sound pressure level, and relatively weak responses to noise. A model of DCN neural circuitry was used to explore two hypothetical mechanisms by which neurons may be endowed with type II unit response properties. Both mechanisms assume that type II units receive excitatory input from auditory nerve (AN) fibers and inhibitory input from an unspecified class of cochlear nucleus interneurons that also receive excitatory AN input. The first mechanism, a lateral inhibition (LI) model, supposes that type II units receive inhibitory input from a number of narrowly tuned interneurons whose best frequencies (BFs) flank the BF of the type II unit. Tonal stimuli near BF result in only weak inhibitory input, but broadband stimuli recruit enough lateral inhibitors to greatly weaken the type II unit response. The second mechanism, a wideband inhibition (WBI) model, supposes that type II units receive inhibitory input from interneurons that are broadly tuned so that they respond more vigorously to broadband stimuli than to tones. Physiological and anatomical evidence points to the possible existence of such a class of neurons in the cochlear nucleus. The model extends an earlier computer model of an iso-frequency DCN patch to multiple frequency slices and adds a population of interneurons to provide the inhibition to model type II units (called I2-cells). The results show that both mechanisms accurately simulate responses of type II units to tones and noise. An experimental paradigm for distinguishing the two mechanisms is proposed. Received: 30 December 1996/Accepted in revised form: 13 March 1997     

Frequency sensitivity of auditory neurons in the Caiman cochlear nucleus

Summary The characteristic frequencies of single auditory neurons in Caiman crocodilus (South American Alligator) range from 70 to 2,900 Hz. These neurons in the cochlear nuclei show a striking tonotopic organization which parallels that in birds. The sensitivity curve of all neurons and the number of neurons in each frequency range show features similar to those of birds and mammals.Supported by NSF. grant GB 5697. I thank Dr. Mark Konishi for overseeing this work.     

Synaptic relations of neurotensinergic neurons in the dorsal raphe nucleus

The ultrastructure and synaptic relations of neurotensinergic neurons in the rat dorsal raphe nucleus (DRN) were examined. The neurotensin-like immunoreactive (NT-LI) neurons in the DRN were fusiform or spherical. The NT-LI perikarya could only be detected in colchicine-treated animals whereas the immunoreactive axon terminals could only be found in the anirnals not treated with colchicine. Although many NT-LI dendrites received synapses from nonimmunoreactive axon terminals, the NT-LI perikarya received few synapses. NT-LI axon terminals also made synapses on nonimmunoreactive dendrites. Occasionally, synapses were found between the NT-LI axon terminals and NT-LI dendrites in the cases in which the animals were not treated with colchicine.     

Multidimensional characterization and differentiation of neurons in the anteroventral cochlear nucleus

Multiple parallel auditory pathways ascend from the cochlear nucleus. It is generally accepted that the origin of these pathways are distinct groups of neurons differing in their anatomical and physiological properties. In extracellular in vivo recordings these neurons are typically classified on the basis of their peri-stimulus time histogram. In the present study we reconsider the question of classification of neurons in the anteroventral cochlear nucleus (AVCN) by taking a wider range of response properties into account. The study aims at a better understanding of the AVCN's functional organization and its significance as the source of different ascending auditory pathways. The analyses were based on 223 neurons recorded in the AVCN of the Mongolian gerbil. The range of analysed parameters encompassed spontaneous activity, frequency coding, sound level coding, as well as temporal coding. In order to categorize the unit sample without any presumptions as to the relevance of certain response parameters, hierarchical cluster analysis and additional principal component analysis were employed which both allow a classification on the basis of a multitude of parameters simultaneously. Even with the presently considered wider range of parameters, high number of neurons and more advanced analytical methods, no clear boundaries emerged which would separate the neurons based on their physiology. At the current resolution of the analysis, we therefore conclude that the AVCN units more likely constitute a multi-dimensional continuum with different physiological characteristics manifested at different poles. However, more complex stimuli could be useful to uncover physiological differences in future studies.     

Auditory information coding by modeled cochlear nucleus neurons

In this paper we use information theory to quantify the information in the output spike trains of modeled cochlear nucleus globular bushy cells (GBCs). GBCs are part of the sound localization pathway. They are known for their precise temporal processing, and they code amplitude modulations with high fidelity. Here we investigated the information transmission for a natural sound, a recorded vowel. We conclude that the maximum information transmission rate for a single neuron was close to 1,050 bits/s, which corresponds to a value of approximately 5.8 bits per spike. For quasi-periodic signals like voiced speech, the transmitted information saturated as word duration increased. In general, approximately 80% of the available information from the spike trains was transmitted within about 20 ms. Transmitted information for speech signals concentrated around formant frequency regions. The efficiency of neural coding was above 60% up to the highest temporal resolution we investigated (20 μs). The increase in transmitted information to that precision indicates that these neurons are able to code information with extremely high fidelity, which is required for sound localization. On the other hand, only 20% of the information was captured when the temporal resolution was reduced to 4 ms. As the temporal resolution of most speech recognition systems is limited to less than 10 ms, this massive information loss might be one of the reasons which are responsible for the lack of noise robustness of these systems.     

Oscillating neurons in the cochlear nucleus: II. Simulation results

A computer model of sustained chopper neurons in the ventral cochlear nucleus is presented and investigated. In the companion paper, the underlying neurophysiological and neuroanatomical data are demonstrated. To explain the preference of chopper neurons for oscillations with periods which are multiples of a 0.4 ms synaptic delay, we suggest a model of circularly connected chopper neurons. In order to simulate chopper neurons within a physiological dynamic range for periodicity encoding, it is necessary to assume that they receive an input from onset neurons. Our computer analysis of the resulting simple neuronal network shows that it can produce stable oscillations. The chopping can be triggered by an amplitude-modulated signal (AM). The dynamic range and the synchronous response of the simulated chopper neurons to AM are enhanced significantly by an additional input from onset neurons. Physiological properties of chopper neurons in the cat, such as mean, standard deviation, and coefficient of variation of the interspike interval are matched precisely by our simulations.     

Thresholds of cat cochlear nucleus neurons to microwave pulses

Action potentials of neurons in cat dorsal and posteroventral cochlear nuclei were recorded extracellularly with glass microelectrodes while the head of the cat was exposed to microwave pulses at 915 MHz using a diathermy applicator. Response thresholds to acoustic tones, acoustic clicks, and microwave pulses were determined for auditory units with characteristic frequencies (CFs) from 278 Hz to 39.2 kHz. Tests with pulsatile stimuli were performed for durations of 20-700 mus, principally 20, 70, and 200 mus. Brainstem midline specific absorption rate (SAR) threshold was as small as 11.1 mW/g per pulse, and specific absorption (SA) threshold was a small as 0.6 muJ/g per pulse. Microwave thresholds were generally lower for CF less than 9 kHz, as were most acoustic thresholds. However, microwave threshold was only weakly related to click threshold and CF-tone threshold of each unit.     

Neural organization and responses to complex stimuli in the dorsal cochlear nucleus.

The dorsal division of the cochlear nucleus (DCN) is the most complex of its subdivisions in terms of both anatomical organization and physiological response types. Hypotheses about the functional role of the DCN in hearing are as yet primitive, in part because the organizational complexity of the DCN has made development of a comprehensive and predictive model of its input-output processing difficult. The responses of DCN cells to complex stimuli, especially filtered noise, are interesting because they demonstrate properties that cannot be predicted, without further assumptions, from responses to narrow band stimuli, such as tones. In this paper, we discuss the functional organization of the DCN, i.e. the morphological organization of synaptic connections within the nucleus and the nature of synaptic interactions between its cells. We then discuss the responses of DCN principal cells to filtered noise stimuli that model the spectral sound localization cues produced by the pinna. These data imply that the DCN plays a role in interpreting sound localization cues; supporting evidence for such a role is discussed.