Parallel auditory pathways: projection patterns of the different neuronal populations in the dorsal and ventral cochlear nuclei

Abstract

The cochlear nuclear complex gives rise to widespread projections to nuclei throughout the brainstem. The projections arise from separate, well-defined populations of cells. None of the cell populations in the cochlear nucleus projects to all brainstem targets, and none of the targets receives inputs from all cell types. The projections of nine distinguishable cell types in the cochlear nucleus—seven in the ventral cochlear nucleus and two in the dorsal cochlear nucleus—are described in this review. Globular bushy cells and two types of spherical bushy cells project to nuclei in the superior olivary complex that play roles in sound localization based on binaural cues. Octopus cells convey precisely timed information to nuclei in the superior olivary complex and lateral lemniscus that, in turn, send inhibitory input to the inferior colliculus. Cochlear root neurons send widespread projections to areas of the reticular formation involved in startle reflexes and autonomic functions. Type I multipolar cells may encode complex features of natural stimuli and send excitatory projections directly to the inferior colliculus. Type II multipolar cells send inhibitory projections to the contralateral cochlear nuclei. Fusiform cells in the dorsal cochlear nucleus appear to be important for the localization of sounds based on spectral cues and send direct excitatory projections to the inferior colliculus. Giant cells in the dorsal cochlear nucleus also project directly to the inferior colliculus; some of them may convey inhibitory inputs to the contralateral cochlear nucleus as well.

Introduction

Since the earliest studies of the organization of the central nervous system, it has been recognized that the cells that constitute the dorsal and ventral cochlear nuclei of the mammalian brain are diverse and highly specialized (e.g. [175]). In the modern era of neuroscience, substantial progress has been made in characterizing and defining cell populations in the cochlear nucleus that give rise to differential projections to a variety of brainstem structures. This review begins with a brief history of the development of current ideas about neuronal types in the cochlear nucleus. The main emphasis of the review is a consideration of the projection patterns of each of the neuronal types that sends axons out of the cochlear nucleus to other auditory and non-auditory structures. Recent reviews discuss much of the same literature from other points of view 62., 188., 193., 265..

Ramón y Cajal [175] illustrated and briefly described a number of morphologically distinct cell types in the cochlear nuclear complex. Later, Lorente de Nó [125] reported that the cochlear nucleus contained “no less than 40 or 50 types of neurons.” He illustrated and named some of the cell types in the dorsal cochlear nucleus, but did not describe the cells in the ventral cochlear nucleus until much later [126]. It was not until the 1960s that systematic studies of the cytoarchitecture of the cochlear nuclei were undertaken. Harrison and coworkers 80., 81., 82., 84., 85. and Osen 157., 158., 160. developed criteria for defining cell types in the cochlear nuclei of rats and cats, respectively. Using stains that allowed visualization of cell bodies and synaptic terminals, they described a number of distinct cell types that were distributed differentially in the ventral and dorsal cochlear nuclei. The morphological differences that are apparent in cell stains can be related to differences in a wide variety of other neuronal properties and have formed the basis for considerable success in the attempt to develop a taxonomy of cell types in the cochlear nucleus.

At about the same time that cell types were being described based on their Nissl-staining characteristics, Brawer et al. [30] used Golgi methods to categorize cells in the cochlear nucleus of the cat. Their classifications have the advantage that they include an analysis of dendritic morphology, whereas the classifications based on cell stains have the advantage that the distribution of the cell types throughout the nucleus can be more thoroughly assessed. To a large extent, it has been possible to demonstrate correspondence between the cell classes defined in these two ways (summarized in [44]). In the current literature, distinct cell populations are usually named according to Osen [157] with modifications based on Brawer et al. [30]. In the ventral cochlear nucleus, they include spherical bushy cells, globular bushy cells, octopus cells, cochlear root neurons (not found in all species), multipolar cells (a heterogeneous class that can be subdivided further as discussed below), small cells and granule cells. In the dorsal cochlear nucleus, the cell populations include fusiform (pyramidal) cells, giant cells, a variety of types of small cells, and granule cells. Each of these cell types will be described in more detail in a later section. Except for a few differences to be mentioned later, cell types in rat and cat appear to be quite similar and are also identifiable in a number of other species, including human 6., 87., 136. and other primates 87., 141.; chinchilla 138., 165.; gerbil 145., 165.; guinea pig 75., 76., 133.; kangaroo rat 45., 251.; mole [114]; mouse 239., 252., 262., 264.; porpoise [162]; rabbit 53., 172. and several species of bats 59., 208., 269..

As cell types in the cochlear nucleus were being defined morphologically during the 1960s, Kiang and Pfeiffer and colleagues were recording from units in the cochlear nucleus and developing classifications based on differences in their response properties to tones (110., 173., 174.; cf. [25]). Alternate classification criteria were developed by Evans and Nelson [57], and the two ways of classifying units were subsequently shown to be complementary (e.g. 212., 263.). The physiological profiles of a number of unit types have been described in detail (reviewed, e.g. in 178., 188., 265.). Recognizing the importance of relating morphologically defined classes to physiologically defined classes, Kiang, Morest and their students 111., 140. collaborated on studies of neurons that could be identified based on their location in restricted parts of the ventral cochlear nucleus. They emphasized the importance of interpreting the results of anatomical, physiological, neurochemical and behavioral studies with reference to a common structural framework.

The development of techniques for filling neurons with markers such as horseradish peroxidase after recording their responses to controlled acoustic stimuli has allowed direct correlations of morphology and physiology 45., 52., 58., 64., 77., 79., 165., 169., 179., 182., 194., 215., 216., 217., 218., 219., 220., 222.. To a large extent, physiological classes and morphological classes have been shown to be congruent (reviewed in [177]). Classifications of cell populations have been extended and refined through considerations of other neuronal properties. Different neuronal types have markedly different intrinsic electrical properties and channel and receptor profiles that correlate with morphological differences 18., 34., 58., 65., 71., 72., 86., 92., 128., 129., 146., 147., 150., 151., 171., 264.. Physiological and anatomical studies have demonstrated distinct patterns of inputs from cochlear and non-cochlear sources 8., 118., 119., 258., 260. and associated differences in the fine structure and synaptic organization of each neuronal type (reviewed, e.g. in [40]; see also, 102., 103.). So much information about many of the cell classes has been collected that it is now possible to develop quite detailed models of their function 19., 28., 35., 77., 89., 90., 109., 176., 192., 244., 257.. Finally, each neuronal population in the cochlear nucleus has unique projection patterns. The projections of the cochlear nucleus and the contributions of each of the recognized cell classes to those projections are the subject of the remainder of this review.

Most of what we know about the projections of the cochlear nuclei was learned from studies using degeneration methods or methods based on axonal transport of various tracers. These studies established the targets and topography of the projections of the subdivisions of the cochlear nucleus, and also provided considerable information about the projections of specific cell types. Only with the development of methodology that allows intracellular injection of tracers, however, has it been possible to visualize the axonal branching patterns of individual neurons. Each of the different approaches has advantages and disadvantages. Extracellular tracing studies have the advantage that large numbers of cells or axons can be labeled so that overall patterns of projections can be appreciated, but they have the disadvantage that it is difficult or impossible to isolate only one population of cells for study. In the best cases, intracellular injection studies allow visualization of both dendritic and axonal morphology and can be combined with electrophysiological characterizations, but they have the disadvantage that relatively few neurons can be studied and that it has generally not been possible to obtain complete filling of both dendrites and axonal arborizations in the same cells 64., 216., 217., 220., 222.. If an injection is made into the cell body, the dendritic tree is often completely filled, but the axon is not. Conversely, if the injection is in the axon, many of the axonal arborizations (although perhaps not all) are filled, but the cell body and dendrites are often not labeled or only poorly labeled. Axonal filling often appears to fade with distance from the injection site. (A comparison of the filling of axons that project to the contralateral nucleus of the lateral lemniscus in cat [216] versus rat [64] suggests that fading of axons is less severe in the smaller brain of the rat, but the latter authors also note that the axons were not always completely filled.) The most definite conclusions about the projection patterns of any one cell type can be reached when the results from a number of studies based on different methods are considered together. To provide a frame of reference for what follows it, the next section contains a brief overview of the projections from the cochlear nucleus based mainly on the results of degeneration and tracer studies. This is followed by more detailed descriptions of the individual cell types and, insofar as possible, their particular projection patterns.