Lateral Superior Olive

Auditory neurons in the mammalian brainstem are involved in several basic computation processes essential for survival; for example, sound localization. Differences in sound intensity between the two ears, so-called interaural level differences (ILDs), provide important spatial cues for localizing sound in the horizontal plane, particularly for animals with high-frequency hearing. The earliest center of ILD detection is the lateral superior olive (LSO), a prominent component of the superior olivary complex (SOC) in the medulla oblongata. LSO neurons receive input from both ears of excitatory and inhibitory nature and perform a subtraction-like process. The LSO has become a model system for studies addressing inhibitory synapses, map formation, and neural plasticity. This review aims to provide an overview of several facets of the LSO, focusing on its functional and anatomical organization, including development and plasticity. Understanding this important ILD detector is fundamental in multiple ways—among others, to analyze central auditory processing disorders and central presbyacusis.

Wiring the Cochlea for Sound Perception

Sound information enters the auditory brainstem via spiral ganglion neurons (SGNs), which reliably encode and transmit information received from sensory hair cells in the cochlea. SGNs form both a structural and a functional bridge between the cochlea and the auditory brainstem beginning early in development, with long-term consequences for the maturation of central auditory circuits. This chapter summarizes the key events in SGN development, from their origin in the early otic vesicle and the emergence of the basic wiring pattern of the cochlea to the elaboration of specialized synapses and the acquisition of diverse firing properties that enable sound perception even within noisy environments. Key cellular events and molecular players are introduced, with emphasis on the impact of reciprocal interactions between the cochlea and the auditory brainstem throughout development.

Axon Trajectories in the Auditory Brainstem

This chapter summarizes what is known about the organization of the axons that make up the white matter of the auditory brainstem. The sources of the axons in each of the major fiber bundles (the dorsal and intermediate acoustic striae, the ventral acoustic stria or trapezoid body, and the lateral lemniscus) are reviewed, and, where information is available, the organization of specific groups of axons within the fiber bundles is described. The chapter collects the extensive but scattered information about axon trajectories into one place, both to provide a summary of what is known and also to indicate important gaps in our knowledge. The emphasis is almost entirely on the routes followed by groups of axons over the relatively long distances between structures and on the organization of specific types of axons within the fiber bundles; information about the termination patterns of the axons can be obtained from the references cited and throughout the chapter. Because knowledge about axon trajectories has considerable practical value (as, for example, in designing and interpreting both anatomical and physiological studies), the most useful information is species specific. Fortunately, at least at our current level of understanding, the components and relative positions of the major fiber bundles are remarkably similar across species (undoubtedly reflecting a common mammalian developmental plan).

The Auditory Brainstem Implant

The auditory brainstem implant (ABI) is a surgically implanted device to electrically stimulate auditory neurons in the cochlear nucleus complex of the brainstem in humans to restore hearing sensations. The ABI is similar in function to a cochlear implant, but overall outcomes are poorer. However, recent applications of the ABI to new patient populations and improvements in surgical technique have led to significant improvements in outcomes. While the ABI provides hearing benefits to patients, the outcomes challenge our understanding of how the brain processes neural patterns of auditory information. The neural pattern of activation produced by an ABI is highly unnatural, yet some patients achieve high levels of speech understanding. Based on a meta-analysis of ABI surgeries and outcomes, a theory is proposed of a specialized sub-system of the cochlear nucleus that is critical for speech understanding.

Deviance Detection and Encoding Acoustic Regularity in the Auditory Midbrain

In the past, there was a rather corticocentric conception of the processing of relationships between sounds that used to mostly relegate the midbrain function to a mere relay. However, increasing neurophysiological evidence demonstrates that the midbrain is, in fact, playing a crucial role in encoding some sorts of regularities present in the flow of acoustic stimulation, adapting the neuronal response for processing efficiency. Midbrain neurons are capable of responding more rapidly and strongly when a new stimulus is not matching to a previously encoded regularity; a phenomenon referred to as deviance detection. This chapter discusses deviance detection evidence in the midbrain, mainly describing the characteristics and mechanisms of stimulus-specific adaptation (SSA), and closing with an interpretation from the standpoint of the predictive coding theory.

The Nuclei of the Lateral Lemniscus

Parallel processing streams guide ascending auditory information through the processing hierarchy of the auditory brainstem. Many of these processing streams converge in the lateral lemnisucus, the fiber bundle that connects the cochlear nuclei and superior olivary complex with the inferior colliculus. The neuronal populations within the lateral lemniscus can be segregated according to their gross structure-function relationships into three distinct nuclei. These nuclei are termed ventral, intermedial, and dorsal nucleus, according to their position within the lemniscal fiber bundle. The complexity of their input pattern increases in an ascending fashion. The three nuclei employ different neurotransmitters and exhibit distinct synaptic and biophysical features. Yet they all share a large heterogeneity. Functionally, the ventral nucleus of the lateral lemniscus has been hypothesized to reduce spectral splatter by generating a rapid, temporally precise feedforward onset inhibition in the inferior colliculus. In the intermedial nucleus of the lateral lemniscus a cross-frequency integration has been observed. The hallmark of the dorsal nucleus of the lateral lemniscus is the generation of a long-lasting inhibition in its contralateral counterpart and the inferior colliculus. This inhibition is proposed to generate a suppression of sound sources during reverberations and could act as a temporal filter capable of removing spurious interaural time differences. While great advances have been made in understanding the role that these nuclei play in auditory processing, the functional diversity of the individual neuronal responsiveness within each nucleus remains largely unsolved.

Neuromodulatory Feedback to the Inferior Colliculus

The inferior colliculus (IC) receives prominent projections from centralized neuromodulatory systems. These systems include extra-auditory clusters of cholinergic, dopaminergic, noradrenergic, and serotonergic neurons. Although these modulatory sites are not explicitly part of the auditory system, they receive projections from primary auditory regions and are responsive to acoustic stimuli. This bidirectional influence suggests the existence of auditory-modulatory feedback loops. A characteristic of neuromodulatory centers is that they integrate inputs from anatomically widespread and functionally diverse sets of brain regions. This connectivity gives neuromodulatory systems the potential to import information into the auditory system on situational variables that accompany acoustic stimuli, such as context, internal state, or experience. Once released, neuromodulators functionally reconfigure auditory circuitry through a variety of receptors expressed by auditory neurons. In addition to shaping ascending auditory information, neuromodulation within the IC influences behaviors that arise subcortically, such as prepulse inhibition of the startle response. Neuromodulatory systems therefore provide a route for integrative behavioral information to access auditory processing from its earliest levels.

Unifying the Midbrain

Commissural fibres interconnecting the two sides of the brain are found at several points along the auditory pathway, thus suggesting their fundamental importance for the analysis of sound. This chapter presents an overview of what is currently known about the anatomy, physiology, and behavioral influences of the commissure of the inferior colliculus (CoIC)—the most prominent brainstem auditory commissure—that reciprocally interconnects the principal nuclei of the auditory midbrain, the inferior colliculi (IC). The primary contribution to the CoIC originates from neurons projecting from one inferior colliculus to the other, with the dorsal cortex and central nucleus providing the most extensive connections. In addition, many ascending and descending auditory centers send projections to the IC via the CoIC, together with diverse sources located outside the classically defined auditory pathway. The degree of interconnection between the two ICs suggests they function as a single entity. Recent in vivo evidence has established that CoIC projections modulate the neural representation of sound frequency, level, and location in the IC, thus indicating an important role for the CoIC in auditory processing. However, there is limited evidence for the influence of the CoIC on auditory behavior. This, together with the diversity of sources projecting via the CoIC, suggest unknown roles that warrant further exploration.

Neuron Types, Intrinsic Circuits, and Plasticity in the Inferior Colliculus

The inferior colliculus is a critical auditory center in the midbrain which virtually acts as a hub of all ascending and descending auditory information flows. Wide variety of neuronal responses to sound is found in the IC, and this variety emerges not only from the wide range of extrinsic afferent inputs, but also from the complex features of the local circuits in the IC, for example, the mosaic pattern of extrinsic fiber termination, the various neuronal types each of which compose different patterns of local connection, and the unique forms of synaptic plasticity de novo. This chapter reviews the recent progress in understanding these features, and identifies the key issues for future research.

The Medial Superior Olivary Nucleus

It doesn’t get any more precise than this: Neurons in the medial superior olive (MSO) in many mammals, including humans, are sensitive to temporal differences between their synaptic inputs of only a few microseconds. These neurons are the basis for our ability to resolve even a 5-μs disparity in the time of arrival of a sound at each ear. This capacity enables humans to discriminate between temporally overlapping sounds based on spatial segregation, as for instance, at a cocktail party or a poster session at a scientific conference. This chapter aims at providing a comprehensive summary on the current state of research regarding the MSO, ranging from cellular and circuit anatomy to subcellular and channel physiology to spatial coding and perception. Consequently, the chapter is subdivided according to these thematic aspects. Nonetheless, while such subdivisions are helpful for providing structure to the reader, they can also convey the inter-dependencies between these topics: for example, when studying the spatial sensitivity of MSO neurons on the mechanistic level, it is crucial to also consider its anatomical specializations (on the subcellular and circuit level), as well as corresponding perceptional phenomena. Finally, the chapter suggests a complete picture of the MSO only emerges by including evolutionary considerations, that is, the phylogenetic origin of the many fascinating specializations that can be observed within the MSO circuit.