Review
The multiple functions of T stellate/multipolar/chopper cells in the ventral cochlear nucleus

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Abstract

Acoustic information is brought to the brain by auditory nerve fibers, all of which terminate in the cochlear nuclei, and is passed up the auditory pathway through the principal cells of the cochlear nuclei. A population of neurons variously known as T stellate, type I multipolar, planar multipolar, or chopper cells forms one of the major ascending auditory pathways through the brainstem. T Stellate cells are sharply tuned; as a population they encode the spectrum of sounds. In these neurons, phasic excitation from the auditory nerve is made more tonic by feedforward excitation, coactivation of inhibitory with excitatory inputs, relatively large excitatory currents through NMDA receptors, and relatively little synaptic depression. The mechanisms that make firing tonic also obscure the fine structure of sounds that is represented in the excitatory inputs from the auditory nerve and account for the characteristic chopping response patterns with which T stellate cells respond to tones. In contrast with other principal cells of the ventral cochlear nucleus (VCN), T stellate cells lack a low-voltage-activated potassium conductance and are therefore sensitive to small, steady, neuromodulating currents. The presence of cholinergic, serotonergic and noradrenergic receptors allows the excitability of these cells to be modulated by medial olivocochlear efferent neurons and by neuronal circuits associated with arousal. T Stellate cells deliver acoustic information to the ipsilateral dorsal cochlear nucleus (DCN), ventral nucleus of the trapezoid body (VNTB), periolivary regions around the lateral superior olivary nucleus (LSO), and to the contralateral ventral lemniscal nuclei (VNLL) and inferior colliculus (IC). It is likely that T stellate cells participate in feedback loops through both medial and lateral olivocochlear efferent neurons and they may be a source of ipsilateral excitation of the LSO.

Highlights

► T Stellate cells encode the spectrum and envelope of sounds, ► These cells convert phasic excitation from the auditory nerve to tonic firing, ► Five mechanisms, some cellular and some as circuits, conspire to produce tonic firing, ► T Stellate cells sense driving inputs through glutamaterigic and glycinergic receptors, ► T stellate cells are modulated through GABA, ACh, 5-HT, and NE receptors.

Introduction

Acoustic information flows into the brain through the cochlear nuclei where the auditory pathway is subdivided into multiple, parallel ascending pathways. An important and interesting one is through stellate (or multipolar) cells of the VCN. Recent findings indicate that these cells and the synapses that feed acoustic information to them are specialized, allowing them to carry different acoustic information than the bushy and octopus cells, the two other major groups of principal cells of the VCN. Individual T stellate cells encode the envelope of sounds in the band of frequencies to which they are tuned, cues that are known to be critical for the understanding of speech (Shannon et al., 1995). As a population, T stellate cells encode spectrum, acoustic information that is used not only for understanding but also for localizing sounds (Blackburn and Sachs, 1990, May et al., 1998).

Most T stellate cells occupy the multipolar cell region of the VCN between the nerve root and the octopus cell area, with a few sitting anterior to the nerve root (Osen, 1969, Lorente de Nó, 1981, Brawer et al., 1974, Oertel et al., 1990, Doucet and Ryugo, 1997, Doucet and Ryugo, 2006). T Stellate cells contact numerous targets in the brainstem, including the olivocochlear efferent neurons, ventral and intermediate nuclei of the lateral lemniscus and inferior colliculus. Here we summarize what functions T stellate cells perform and how cellular features support those functions.

Section snippets

Definitions of stellate/multipolar/chopper cells

T Stellate cells were identified in a variety of ways and were eventually found to correspond to a single cell type. Early studies named them “multipolar” (on the basis of Nissl staining) and “stellate” (on the basis of Golgi impregnation) cells (Osen, 1969, Brawer et al., 1974, Lorente de Nó, 1981). It then became clear that there were two distinct types of multipolar/stellate cells. Cant showed that “type I” and “type II” multipolar cells in cats differed in their somatic innervation (Cant,

T stellate cells respond to sound by firing tonically

Tones evoke regular, tonic firing in T stellate cells whose rate increases monotonically with intensity (Rhode and Smith, 1986, Young et al., 1988, Blackburn and Sachs, 1989) (Fig. 2A). The timing of action potentials is so reproducible that peristimulus time histograms have modes that are strong and sharp at the onset of the response and weaken as temporal jitter accumulates over the duration of the response to tones (Rhode et al., 1983, Smith and Rhode, 1989, Blackburn and Sachs, 1989) (Fig. 2

Multiple mechanisms enable T stellate cells to make phasic excitation more tonic

The observation that chopping can be generated in T stellate cells simply by applying steady depolarizing current (Oertel et al., 1988) was initially surprising because excitation by auditory nerve fibers would be expected to be large excitatory synaptic currents at the onset of a tone when auditory nerve fibers fire most rapidly and then to decrease as the firing rate of auditory nerve fibers adapts. It is now clear that five mechanisms conspire to enable tonic firing.

The mechanisms that enhance tonic firing obscure the encoding of temporal fine structure of sounds

The onset of the chopper response is dominated by excitation from auditory nerve fibers and would thus be expected to reflect the timing of the arrival of signals through auditory nerve fibers, similarly as in other principal cells of the VCN. Surprisingly, the latency between the onset of a tone and the first spike of chopper responses to tones has a small standard deviation but is about 1 ms longer than that of the other principal cells (van Gisbergen et al., 1975, Young et al., 1988). These

T stellate cells are affected by neuromodulatory as well as driving inputs

T Stellate cells differ from other principal cells of the VCN in their sensitivity to neuromodulatory currents. Their relatively high input resistances allow small currents to cause relatively large voltage changes to produce firing (Fujino and Oertel, 2001). T Stellate cells lack the low-voltage-activated potassium conductance that reduces repetitive firing in bushy and octopus cells (Ferragamo and Oertel, 2002, McGinley and Oertel, 2006). The low-voltage-activated potassium conductance also

T stellate cells form a major ascending auditory pathway through the brainstem

The prominence of T stellate cells in the brainstem auditory pathways can be appreciated by their projections. T Stellate cells have targets within the cochlear nuclei and in addition form one of the major ascending pathways through the brainstem (reviewed by Doucet and Ryugo, 2006). Their projections are summarized in Fig. 4.

Axons of T stellate cells exit the VCN through the trapezoid body, cross the midline and ultimately terminate in the contralateral inferior colliculus (Adams, 1979).

Birds have neurons that share many of the features of T stellate cells

The cochlear nuclei have been studied extensively in birds. Nucleus angularis receives innervation from auditory nerve fibers and contains neurons that bear a strong resemblance to T stellate cells. The heterogeneous dendritic morphologies indicate that nucleus angularis holds multiple types and that not all neurons in nucleus angularis bear homology to T stellate cells (Soares and Carr, 2001). Neurons in nucleus angularis project to the lemniscal nuclei and to the inferior colliculus (

Summary

As a population, T stellate cells encode the spectrum of sounds. They receive acoustic input from auditory nerve fibers whose phasic firing emphasizes changes in intensity and convert them to more tonic responses. Several mechanisms contribute to that transformation: Feedforward excitation through other T stellate cells, coactivation of excitation and inhibition, reduction in synaptic depression, and the amplification of excitatory synaptic current over time through NMDA receptors. They deliver

Acknowledgements

Many colleagues contributed to this work over many years. We are especially grateful to Shu Hui Wu, Robert Wickesberg, Nace Golding, and Aldo Rodrigues. We also thank Ravi Kochhar, Inge Siggelkow, Jo Ann Ekleberry, and members of the office staff whose help and support has been critical and longstanding. We also thank Jennifer Seifert for her professional editorial input. This work was supported by a grant from the NIH DC00176.

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