Information

processing

in the auditory

brainstem

Albert S. Feng University

The past year structural

has seen significant

(circuitry

characteristics

of Illinois, Urbana,

advances

and chemistry

of

the

shed light on the

brainstem. underlying

processing

Current

Opinion

in Neurobiology

cochlear

of neural

function

Some

of

complex

of the

and functional

the

findings

auditory

that

information

1992, 2:511-515

eighth nerve fibers possessing similar CFs. Neurons with higher (I-3kHz) CFs also showed strong phase-locked responses when presented with tones of < 1 kHz. The mechanism responsible for this sharpening of phaselocked responses in the CN is not known and should be rigorously pursued.

The auditory brainstem is an important locus for infor mation processing. Stimulus coding in cochlear atferent fibers undergoes dramatic transformations in the brainstem, such that different sound attributes can be accurately represented in the upper brainstem and cortex. The auditory brainstem has five major processing centers each of which possesses at least three distinct subdivisions having specific innervation patterns. With more refined anatomical, biochemical labeling, physiological recording, and system analytical techniques, the past year has seen continued and rapid advances in our knowledge of the structure and function of each of the brainstem nuclei. This review will focus on some of the findings that are enhancing our understanding of the mechanisms underlying complex auditory information processing.

correlates

connections)

are highlighted.

Introduction

Structural

in our understanding

of synaptic

auditory

mechanisms

Illinois, USA

Axons of GB cells give one to four collateral branches ipsilaterally that terminate in specific nuclei in the superior olive (Fig.1). Contralaterally, they give rise to one or two calyces of Held in the main nucleus of the trapezoid body (MNTB). Taken together, these results suggest that there is a much tighter correlation between the structural and physiological attributes of GB cells than previously believed. In the anteroventral cochlear nucleus (AVCN), the mechanisms underlying the chopper discharge patterns of stellate cells have been investigated using an equivalent cylinder compartmental model [2*]. Chopper units are known to display varying degrees of adaptation and firing regularity. Banks and Sachs [2*] found that by increasing the number of excitatory synaptic inputs onto the model neuron, the firing regularity could be enhanced. The geometry, specifically the distance of these terminals to the soma, was less influential. It is therefore possible that such extrinsic factors, together with the intrinsic characteristics of stellate cell membrane (revealed by Oertel and colleagues), are directly responsible for generating rhythmic firing patterns in these neurons. When inhibitory inputs were activated, the sustained chopping pattern was converted into a transient pattern, and the chopping also became less regular. The specific origin of the inhibitory inputs to stellate cells is not clear. It is not known whether or not it involves the topographic projection from dorsal to ventral cochlear nuclei and the glycinergic synapses that have been revealed previously [3,4]. Activation of this pathway has been shown to inhibit bushy and stellate cells as well as multipolar cells in

in the

nucleus

The mammalian cochlear nucleus (CN) has three major subdivisions (anteroventral, posteroventral and dorsal), each of which receives a complete frequency representation from the cochlea and contains distinct morphological cell types. Recent studies have focused on determining whether or not each cell type possesses specific response properties and connectivity patterns. Through intracellular recording and subsequent horseradish peroxidase injection into axons of globular bushy (GB) cells in ventral divisions of the CN, Smith et al. [ 1.1 found that all GB neurons possess specific temporal discharge patterns: primary-like with notch, or onset with low sustained activity. Cells with low characteristic frequencies (CF) < 1 kHz, showed exceptionally high degrees of response synchrony to tones at CFs when compared with

Abbreviations AVCN-anteroventral

cochlear nucleus; CF-characteristic

GB-globular ICx--external MNTB-main

bushy

nucleus nucleus

cell; K-inferior

of the inferior

of the trapezoid

NMDA-N-methyl-o-aspartate; @

colliculus;

Kc--central

IPDinteraural

body; MS-medial SB-spherical

Current

nucleus;

frequency, CN-cochlear

colliculus;

Biology

nucleus

phase difference; superior

bushy

cell; SOC-superior

acid;

colliculus;

LSO-lateral

olive; NLL-nucleus

Ltd ISSN 09594388

CABA-y-aminobutyric

of the inferior

superior

olive;

of the lateral lemniscus;

olivary

complex.

511

512

Sensory

systems

Fig.1. From contralateral

A

caudal

SB

the

schematic

auditory

connectivity

groups vary

in the

diagram

brainstem

of

the

illustrating

patterns

of major

cell

mammalian

superior

oli-

complex.

Only

two

cell types

in

the cochlear

nucleus

the spherical

bushy ES) and the globular

bushy

(GE) cells. CB cells supply excita-

tory afferents nucleus

to the contralateral

of the

trapezoid

and the ipsilateral trapezoid tions

(CN) are depicted,

body

are

main

body

lateral

(MNTB)

nucleus

(LNTB).

as illustrated

of the

Other

projec-

in the

diagram

(for more details, see [l*I). The excitatory neurotransmitter

for MNTB (1) is proba-

bly glutaminergic to aspartate) unknown. provide

(not

The MNTB inhibitory

ipsilateral

medial

superior

these

CABA

glycine

and/or

excitatory

cells in the AVCN

\\

I I

To contralateral VNLL +------

From contralateral

and

MNTB

DMPO ______r-__

excitatory

\ \

PPO,

[81. The MS0

from

both

are not known. of the

nucleus

(LSO) is probably

non-NMDA projections

lateral

Chemical

messengers

in the superior

olivary

complex The side takes The

process by which auditory information from one of the brain is transmitted to the opposite side place in the superior olivaq complex (SOC) [7]. acoustic chiasm is generated by a twostdge process involving a convergence of inputs from the two ears, in order that audito? hemifields can be represented

SB

sides; the (4) for this

lpsilateral

ex-

olivary

mediated

by

(quisquafate)

projection

(5) from

MNTB (which is excited

CB cells from the contralateral

By carefully mapping response areas (in frequencyintensity planes) of 49 type IV neurons in the DCN, Spirou and Young 161 concluded that these neurons were characterized by two excitatory and two inhibitory regions, with the low-threshold excitatory region near the unit’s CF, *and the inhibitory region at higher levels around the CF, being predominant. When presented with noise, these units show excitatory responses with a narrow notch, but inhibitory responses with wider notches. These results confirm the previous hypothesis that responses of type IL’ units to noise cannot be predicted from summated responses to tones, but can be explained in terms of inhibitory inputs from type II units and the organization of their connections to type IV units.

also

(6) from SB cells. The LSO re-

a glycinergic

the ipsilateral

the VCN, and functionally it serves to suppress responses to short-latency echoes, for instance from sound reflection from the walls in a room [4,5].

from

superior

glutaminergic

nu-

involve

projections

citation

ceives

GB

olivary

presumably

neurotransmitters

pathway To ipsilateral

and LNTB in turn

inputs (2 and 3) to the

cleus (MSO); receives

immunoreactive

and that for LNTB (7) is still

by

CN).

in the system, and a subsequent distribution of information to the appropriate side of the system (Fig.1). The lateral superior olive (1.~0) plays a key role in this process. Principal neurons in the IS0 receive peridendritic excitatory inputs from spherical bushy (SE) cells in the ipsilateral AVCN, and perisomatic inhibitory inputs from the GB cells of the contralateral CN via the ipsilateral MNTB. The chemical messengers of the acoustic chiasm are not precisely known except that contralateral inhibition of IS0 neurons is most likely mediated by glycine [8] ~ New results deriving from immunohistochemical and high-affinity uptake studies [9**] confirm that perisomatic terminals from the MN’I’B are glyciner gic. In addition, MNTF3 neurons themselves are immunoreactive to the glycine antibody, Perisomatic terminals that were labeled by horseradish peroxidase following an injection into the ipsilateral MNTB were also labeled by the high-affinity uptake of tritiated glycine. In the lateral limb, in contrast to previous findings [ I()], new data [9**] reveal that the densities of glycinergic terminals and rem ceptors are not significantly different from those found elsewhere in the LSO. Given that the lateral limb of the LSO receives fewer afferents from the MNTB in comparison with the medial and middle limbs, these data indicate that some of the glycinergic terminals in this region may originate from sources other than the MNTEL A recent tract tracing study [ 111 has shown that in addition to AVCN-IS0 and INTE--ISO projections, there is a distinct PVCN-LSO projection, but whether or not this is glycinergic is not known.

Information processing in the auditory brainstem Feng

The identity of the neurotransmitter for ipsilateral excitation of IS0 neurons through peridendritic synapses is not well established. It probably involves non-N-methylb-aspartate (NMDA) glutamate receptors [8]. New evi dence [9**] suggests that quisqualate, and not kainate, is the likely neurotransmitter in this pathway. In a recent physiological study involving the IS0 [12-l, Finlayson and Caspaty found that, similar to high-frequency IS0 neurons in the medial and middle limbs, all low-frequency neurons from the lateral limb were excited by ipsilateral stimuli and inhibited by contralateral stimuli. Furthermore, these low-frequency neurons were not only sensitive to interaural intensity difference, as are high-CF neurons in the ISO, but also to interaural phase difference (IPD). Data from intracellular in vitro [13,14] have shown that the binrecordings aural sensitivities of IS0 neurons are probably a result of the interplay of excitatory and inhibitory synaptic potentials arising, respectively, from the ipsilateral CN and MNTB (which receive contralateral excitation). The finding that IS0 neurons are sensitive to IPD, an attribute previously thought to be unique to low-CF neurons in the medial superior olive (MSO), raises an interesting question. Namely, does the dichotomy of binaural processing of intensity by the IS0 and time by the MS0 hold for all mammals, or are there different degrees of variation on this theme?

Physiological

properties

of neurons

of the lateral

lemniscus

and inferior

in nuclei colliculus

Three nuclei of the lateral lemniscus (NLL) are observed in all mammals: dorsal (DNLL), intermediate (INLL) and ventral (VNLL). The DNLL, which receives projections from the SOC, is a binaural system, but the INLL and WILL, which receive input mainly from the contralateral CN, are primarily monaural. Physiological recordings [ 151 from the INLL and two subdivisions of VNLL, the columnar VNLL and multipolar VNLL cell areas, in the big brown bat have shown that each subdivision contains a complete tonotopic representation. Furthermore, virtually all units were monaural, had broad frequencytuning curves, little or no spontaneous activity, and responded most robustly to stimuli having durations of < 5 ms. In particular, the columnar VNLL neurons had the broadest tuning curves, no spontaneous activity, and gave only a single spike of constant latency (jitter was -=z30 us), independent of frequency and intensity. These data suggest that the two VNLL divisions and the INLL, are not only morphologically but also functionally distinct. It has been hypothesized that the columnar VNLL is specialized in accurate representation of sound onset, and the INLL and multipolar VNLL in processing ongoing time. No compelling evidence has been provided for the latter assertion, however The inferior colliculus (IC) receives converging inputs from binaural and monaural systems in the lower brainstem and plays a key role in representations of space and

other sound attributes. Aitkin [16] has investigated how sound intensity is represented in the central nucleus of the IC (ICC) using more natural free-field stimulation. The rate-level functions (firing rate versus sound level) of single units were derived at three different azimuths (right 45”, left 45”and midline). Two-thirds of ICC units exhibited non-monotonic rate-level functions (firing rate first increased then decreased with sound level) in response to tones at the unit’s CF. The rate-level function shifted systematically with direction. When noise was used as a stimulus, the non-monotonic rate-level function to pure tones became monotonic. Thus, the firing rate is an am biguous measure of sound level, as rate-level function is non-monotonic and depends on sound direction and spectrum. These results point to the need for a large network of neurons for unambiguous representation of any sound attribute, including sound intensity. Presumably, many neurons must interact and cooperate to extract such information. Recent evidence deriving from intracellular recordings from the IC [ 171 has indeed revealed that IC neurons possess extensive local axonal collaterals, in addition to long projection axons, for local interactions.

Role of CABA in central

auditory

processing

y-Aminobutyric acid (GABA) has been implicated in auditory processing in various pathways. Faingold and colleagues [18] demonstrated that GABA was likely to be responsible for the non-monotonic rate-level function evinced in the ICC, and for shaping the phasic discharge patterns of ICC neurons. Application of bicuculline (a GABA* antagonist) altered the rate-level function from non-monotonic to monotonic; this effect was primarily mediated by disinhibition of the sustained component of responses at high intensities, implying that GABA may be responsible for the phasic discharge patterns observed in the control, A separate study in owls [ 19**] has also suggested that GABA is involved in the creation of phasic patterns that are better suited for encoding time-varying stimuli than are tonic patterns. Administration of bicuculline methiodide altered the temporal discharge patterns of ICC and external nucleus of IC (ICx) neurons from predominantly phasic patterns to more tonic patterns [ 19**]. GABA may also play a role in binaural inhibition. For many IC neurons, the response to contralateral stimulation is reduced by simultaneous ipsilateral stimulation. This ipsilateral inhibition is blocked by the application of bicuculline [ 181. More elegantly, GABA has been shown to be involved in sharpening the spatial receptive fields of auditory neurons in barn owls [19.-l. Fujita and Konishi investigated neural sensitivity to IPD (the main cue for horizontal sound localization) in different brainstem nuclei in barn owls. In response to binaural tonal stimuli, neurons in the lower brainstem (nucleus laminaris and the anterior portion of the VNLL) showed similar selectivities to IPDs; they exhibited cyclical response curves with peaks separated by a time equal to the period of the

513

Functional

organization

of the auditory

cortex:

maps and mechanisms Christoph E. Schreiner University

Recent

studies

the organization of information revealed

new

connections,

of California,

have

San Francisco,

led to a better

and physiological

understanding

mechanisms

California,

of several

involved

USA

aspects

in the auditory cortex. A wide range of approaches information single-unit

well as mechanisms

regarding

physiology,

histochemistry,

and functional

and effects of representational cortical

Current

the

Opinion

Significant progress has been made in our understanding of the structural and functional organization of manmalian and avian auditory cortices over the past few decades. Some aspects of this increased understanding have recently been summarized in a number of reviews [l-+,5,6]. Despite these advances, a global and detailed understanding of auditory cortical function is comparatively still quite limited. An exception to this assessment represents our understanding of the auditory cortex of echo-locating bats (see [5,7] >. Because of the unique behavioral specialization of these animals, many aspects of their auditory cortical organization that can be linked to their special behavior have been unraveled. The success in transferring some of the knowledge obtained from these specialized animals to the cortical function of acoustically non- or less-specialized animals has been limited, however. Among the difficulties in exploring the functional organization of auditory cortex in non-specialized animals are a limited understanding of the behaviorally important acoustical elements in the environments of different species, and the detection, discrimination, and categorization strategies employed by the animals. Detailed knowledge of these aspects of the extremely limited and interpretationally more accessible biosonar signal repertoire has led to the identification of highly systematic and smooth spatial representations of several biosonar parameters across the cortical surface of bats. The importance of these cortical maps for the perception of biosonar signals has recently been demonstrated by Riquimaroux and colleagues [@*I who selectively inactivated two cortical maps, one involved in frequency discrimination and one involved in temporal discrimination, by injection of muscimol, a y-aminobutyric acid (GABA) antagonist, into those cortical areas. The inactivation of an area resulted in either frequency

have

corticocortical

spatial organization,

as

and learning-induced

plasticity.

in Neurobiology

Introduction

of

in the processing

1992, 2:516-521

or temporal discrimination deficits (see also [9]> that were predictable from the electrophysiologically determined parameters mapped in each field. This finding provides an important and convincing link between cortical functional representations and behavior. With the exception of frequency organization, no equally systematic and behaviorally significant ‘representational maps’ have been unequivocally identified in the auditory cortex of any other mammal. A number of basic physiological response parameters of cortical auditory neurons, among them sharpness of frequency tuning [ lO,ll], intensity tuning [ 121, binaural interaction [13,14], onset latency (CE Schreiner et al: Assoc Res Otolayngol Ab str 1988, 11:36) [ 151, and periodic@ coding [ 16,171 appear to show spatial distribution characteristics that are reminiscent of representational maps, namely spatial clustering of similar response properties or gradual spatial changes of a given response property. Different auditory cortical areas may show distinctly different ranges of these response properties, and each cortical location may be characterized by a different combination of these basic characteristics (‘combination sensitivity’). At the present time it remains to be seen how the different combinations of functionally significant response properties in each neuron contribute to the undoubtedly highly complex cortical representation of behaviorally significant acoustic signals. It is likely that the role of combination sensitivity for cortical neurons will be defined in connection with the following principles: first, as part of a general representation of a multi-dimensional acoustical ‘parameter space’ in a two-dimensional cortical space resulting in a locally smooth, but globally fractured, representation of acoustic information, as is found in some visual cortical areas; second, as part of as yet undefined smooth cortical representational maps of behaviorally significant perceptual dimensions, as sug-

Abbreviations AA&anterior

516

auditory field; AChE-acetylcholinesterase; Al-primary auditory cortical field; All-secondary auditory cortical field; CABA--y-aminobutyric acid; PAF-posterior auditory field; VPAF-ventroposterior auditory field. @ Current Biology Ltd ISSN 09594388

Functional organization of the auditory cortex Schreiner

gested by the bat studies; and third, as part of a hierarchical, parallel, and serial arrangement system with hierarchically increasing functional specialization, as suggested by other sensory modalities (for an example, see [18]) and the findings in bats. To arrive at a unilied picture of the cortical functional representations of the acoustical environment, different methodological as well as conceptual approaches have to be used. These include morphological and functional descriptions of single functional elements, histochemical and chemoarchitectonic aspects, descriptions of functional cell assemblies and their interconnections, global distributions of projectional and functional as pects within and between different cortical fields, developmentally and behaviorally driven morphological and functional changes, as well as the establishment of behavioral frameworks that allow an appropriate interpretation of the observed functional capacities. This review, which represents an extension of the review that appeared in last year’s issue [l*], will discuss recent contributions to several of these topics.

Chemoarchitectonic auditory

organization

of primary

cortex

A complete and unequivocal delineation of the extent of the primary auditory cortical field (AI) is rather difficult when applying physiological, cytoarchitectonic, and/or projectional criteria [ 19241 as,with the exception of the reversal of the frequency gradient at the anterior and posterior end of AI, the borders with the surrounding fields are not well defined and are compromised by the influence of the sulcal pattern. Wallace and coworkers [25-l have proposed a chemoarchitectonic approach that appears to delineate more clearly an area that corresponds to AI as delined by cytoarchitectonic and physiological criteria. Strong activity levels of acetylcholinesterase (AChE) in layers III, IV, and VI appear to be restricted to AI. A similar delineation can be based on the distribution of monoclonal antibody CAT 301-positive cells. Al though a more precise assessment of the congruence of the AChE delined area with the physiologically defined AI has still to be performed, these findings may help resolve the uncertainty of whether the dorsal portion of the ectosylvian sulcus (the ‘dorsal zone of AI’ [ 10,20,24,26**] ) is part of AI proper, represents a transition zone, or is an independent area. Physiologically, this area differs somewhat from traditional AI properties, but no clear functional discontinuities have been found to support its conceptual segregation from AI. The AChE activity shows no clear difference between AI proper and the dorsal zone. With regard to another aspect of the histochemical exploration of auditory cortex, Hendry and Jones 127.1 have investigated details of the previously described presence of GABA-immunoreactive neurons in AI [28], Similar to cortical areas of other modalities, a distribution of several subpopulations of GABA neurons was identified, with

differences in their laminar distribution. GABA neurons were found colocalized with the Ca2+ -binding proteins, calbindin (most prominently in layers II, IIIA and VI), and parvalbumine (prominently seen in layers IIIB, IV and VI). Ca2+ protein negative GABA neurons were seen mostly in layers I and also in layer II. Functional distinctions between these different inhibitory neurons are at this time only speculative, as details of the spatial and laminar distribution of inhibitory influences on the physiology of auditory cortical neurons are scarce.

lntracortical

connections

Previous physiological and projectional studies provided evidence for a somewhat ‘patchy’ organization of cat AI. In the spatial extent, orthogonal to the frequency gradient (the ‘isofrequency domain’), binaural interaction/sound localization properties appear to show some banding or clustering of similar response characteristics [ 13,14,29,30]. A related patchiness is observed for the innervation by commissural fibers [ 311. Intrinsic connections in AI also appear to be patchy rather than continuous [32]. Three recent studies [ 33*,34**,35] have elaborated on these observations by studying the axonal collateralization of single neurons (using intracellular injection of horseradish peroxidase [33*] ) and groups of neurons (using extracellular injection of Pbaseolus vulgad leucoagglutinin [ 34**,35] >, and their relationship to the frequency organization of AI. The results include: support for previous evidence [ 361 that the major spread of excitation in AI, mediated by horizontal collaterals of pyramidal cells, occurs along the axis of the isofrequency domain; evidence that the terminal arborizations of the intracortical collaterals are columnar; observations of two to eight dorso-ventrally oriented patches of terminal labeling in AI, some of them as far as 1.5 mm away from the parent cell(s), and not always closely aligned with the original isofrequency contour (some patches were outside of AI); and the finding that intrinsic connections arising from nearby cylinders of neurons are usually not homogeneous. These results provide further evidence that the isofrequency domain in AI may be functionally subdivided. Matsubara and Phillips [32] have shown that patches arising from the same injection do not necessarily have identical binaural properties. The functional implications of this organizational patchiness of AI are intriguing especially with regard to interconnected patches of different frequency. Besides being potentially related to the occurrence of neurons with multi-peaked tuning curves in AI (see below) [26**,37], this type of organization establishes constraints on the type of functional representations realized in AI (see Introduction), and the type and magnitude of interactions between cortical locations with similar or different combination sensitivities to functional characteristics. In an important and the laminar connections in cortex, evidence

study of the transcallosal projections arrangement of corticocortical interthe major five fields of cat auditory for parallel and hierarchical process-

517

Information processing in the auditory brainstem.

The past year has seen significant advances in our understanding of the structural (circuitry and chemistry of synaptic connections) and functional ch...
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