Species Differences in the Organization of the Ventral Cochlear Nucleus

The mammalian cochlear nuclei (CN) consist of two major subdivisions, the dorsal (DCN) and ventral (VCN) nuclei. We previously reported differences in the structural and neurochemical organization of the human DCN from that in several other species. Here we extend this analysis to the VCN, considering both the organization of subdivisions and the types and distributions of neurons. Classically, the VCN in mammals is composed of two subdivisions, the anteroventral (VCA) and posteroventral cochlear nuclei (VCP). Anatomical and electrophysiological data in several species have defined distinct neuronal types with different distributions in the VCA and VCP. We asked if VCN subdivisions and anatomically defined neuronal types might be distinguished by patterns of protein expression in humans. We also asked if the neurochemical characteristics of the VCN are the same in humans as in other mammalian species, analyzing data from chimpanzees, macaque monkeys, cats, rats and chinchillas. We examined Nissl‐ and immunostained sections, using antibodies that had labeled neurons in other brainstem nuclei in humans. Nissl‐stained sections supported the presence of both VCP and VCA in humans and chimpanzees. However, patterns of protein expression did not differentiate classes of neurons in humans; neurons of different soma shapes and dendritic configurations all expressed the same proteins. The patterns of immunostaining in macaque monkey, cat, rat, and chinchilla were different from those in humans and chimpanzees and from each other. The results may correlate with species differences in auditory function and plasticity. Anat Rec, 301:862–886, 2018. © 2017 Wiley Periodicals, Inc.     

The cochlear nuclei in man

The human cochlear nuclei are composed of a ventral and a dorsal nucleus which are similar, though not identical, in their cytoarchitecture to those of other mammals. The ventral cochlear nucleus (VCN) consists of a rostral area of spherical cells, a central area of multipolar and globular cells, a posterior area of octopus cells, and a laterodorsal cap of small neurons. The interareal boundaries are less distinct in man than in the cat. The central region of multipolar cells and the cap area of small cells constitute the bulk of the human VCN. The spherical, globular, and octopus cells appear relatively less numerous in man than in other mammals. The dorsal cochlear nucleus (DCN) in man is relatively large, but lacks the typical stratification seen in other mammals, with only vestiges of the granular and molecular layers remaining. Virtually the entire DCN consists of an area of cochlear fiber neuropil containing pyramidal cells, small neurons, and occasional giant cells. The pyramidal cells have lost their typical radial orientation and lie scattered within the cochlear neuropil. Thus the entire human DCN may be equivalent to layers 2 and 3 of this nucleus in other mammals. In spite of the relatively large DCN, the acoustic striae appear small. This is in contrast to the large trapezoid body leaving the VCN. Intrinsic and descending fiber pathways to the cochlear nuclei are not clearly defined and may be less prominent in man than in the cat.     

Changing population of neurons and glia in the human cochlear nucleus with progressive age – A stereological study

IntroductionThe human cochlear nucleus (CN) is populated by morphologically diverse types of neurons that contribute specifically in the formation of the complex functional networks in the auditory pathway. On the basis of cytoarchitecture and topography different types of neurons can be identified in the CN. The present study was undertaken to investigate the morphological parameters of neurons and glia of the human CN with aging.MethodsForty-one brainstems (Birth-90 years) from cadaveric donors were collected from the mortuary of the All India Institute of Medical Sciences (AIIMS), New Delhi, with ethical committee permission. They were grouped into nine decades and processed for light microscopy and morphometry. Hierarchical clustering was done to classify the neuron population according to their neuronal and nuclear area into different clusters.ResultsThere was a gradual increase in the mean neuronal and neuronal nucleus volume from decade 1 to 3. Decade 1 had minimum and 3 had maximum nuclear volume and neuron number respectively. An increase in total glial population was observed in decade 9. Eight neuron clusters were identified which were present in the decades 2 and 3 whereas decades 1 and 4 had seven, decades 5–8 had six and decade 9 had four clusters respectively.DiscussionMajor changes were observed within the clusters from middle to old age, especially after decade 5. This may be useful in explaining the vulnerability of some specific subpopulation of neurons more than others and understanding the pathophysiology of altered hearing loss with age.     

Structural and functional classes of multipolar cells in the ventral cochlear nucleus

Multipolar cells in the ventral cochlear nucleus (VCN) are a structurally and functionally diverse group of projection neurons. Understanding their role in the ascending pathway involves partitioning multipolar cells into distinct populations and determining where in the brain each sends its coded messages. In this study, we used retrograde labeling techniques in rats to identify multipolar neurons that project their axons to the ipsilateral dorsal cochlear nucleus (DCN), the contralateral CN, or both structures. Three rats received injections of biotinylated dextran amine in the ipsilateral DCN and diamidino yellow in the contralateral CN. Several radiate multipolar neurons (defined by their axonal projections to the ipsilateral DCN and their dendrites that traverse VCN isofrequency sheets) were double-labeled but over 70% were not. This result suggests two distinct populations: (1) radiate-commissural (RC) multipolar cells that project to the ipsilateral DCN and the contralateral CN, and (2) radiate multipolar cells that project exclusively (in this context) to the ipsilateral DCN. In a different group of animals, we retrogradely labeled multipolar neurons that project their axons to the contralateral CN and measured the size of their cell bodies. The mean size of this population (266 +/- 156 microm2) was significantly smaller than those of RC-multipolar cells (418 +/- 140 microm2). We conclude that the CN commissural pathway is composed of at least two components: (1) RC multipolar cells and (2) commissural multipolar cells that are small- and medium-sized neurons that project exclusively (in this context) to the contralateral CN. These results identify separate structural groups of multipolar cells that may correspond to physiological unit types described in the literature. They also provide protocols for isolating and studying different populations of multipolar cells to determine the neural mechanisms that govern their responses to sound.     

Discharge properties of identified cochlear nucleus neurons and auditory nerve fibers in response to repetitive electrical stimulation of the auditory nerve

Using the in vitro isolated whole brain preparation of the guinea pig maintained at 29°C, we intracellularly recorded and stained cochlear nucleus (CN) neurons and auditory nerve (AN) fibers. Discharge properties of CN cells and AN axons were tested in response to 50-ms trains of electrical pulses delivered to the AN at rates ranging from 100 to 1000 pulses per second (pps). At low stimulation rates (200–300 pps), the discharges of AN fibers and a large proportion of principal cells (bushy, octopus, stellate) in the ventral cochlear nucleus (VCN) followed with high probability each pulse in the train, resulting in synchronization of discharges within large populations of AN fibers and CN cells. In contrast, at high stimulation rates (500 pps and higher), AN fibers and many VCN cells exhibited "primary-like", "onset" and some other discharge patterns resembling those produced by natural sound stimuli. Unlike cells in the VCN, principal cells (pyramidal, giant) of the dorsal CN did not follow the stimulating pulses even at low rates. Instead, they often showed "pauser" and "build-up" patterns of activity, characteristic for these cells in conditions of normal hearing. We hypothesize that, at low stimulation rates, the response behavior of AN fibers and VCN cells is different from the patterns of neuronal activity related to normal auditory processing, whereas high stimulation rates produce more physiologically meaningful discharge patterns. The observed differences in discharge properties of AN fibers and CN cells at different stimulation rates can contribute to significant advantages of high- versus low-rate electrical stimulation of the AN used for coding sounds in modern cochlear implants.     

Laminar and Neurochemical Organization of the Dorsal Cochlear Nucleus of the Human,Monkey, Cat,and Rodents

The dorsal cochlear nucleus (DCN) is a brainstem structure that receives input from the auditory nerve. Many studies in a diversity of species have shown that the DCN has a laminar organization and identifiable neuron types with predictable synaptic relations to each other. In contrast, studies on the human DCN have found a less distinct laminar organization and fewer cell types, although there has been disagreement among studies in how to characterize laminar organization and which of the cell types identified in other animals are also present in humans. We have reexamined DCN organization in the human using immunohistochemistry to analyze the expression of several proteins that have been useful in delineating the neurochemical organization of other brainstem structures in humans: nonphosphorylated neurofilament protein (NPNFP), nitric oxide synthase (nNOS), and three calcium‐binding proteins. The results for humans suggest a laminar organization with only two layers, and the presence of large projection neurons that are enriched in NPNFP. We did not observe evidence in humans of the inhibitory interneurons that have been described in the cat and rodent DCN. To compare humans and other animals directly we used immunohistochemistry to examine the DCN in the macaque monkey, the cat, and three rodents. We found similarities between macaque monkey and human in the expression of NPNFP and nNOS, and unexpected differences among species in the patterns of expression of the calcium‐binding proteins. Anat Rec, 297:1865–1884, 2014. © 2014 Wiley Periodicals, Inc.     

Functional organization of the dorsal cochlear nucleus of the horseshoe bat (Rhinolophus rouxi) studied by GABA and glycine immunocytochemistry and electron microscopy

Unique among mammals, the dorsal cochlear nucleus (DCN) of horseshoe bats consists of two functionally and anatomically distinct subdivisions: a laminated ventral portion that processes the frequency range below the constant frequency (CF) component of the echolocation signal and a nonlaminated dorsal portion that is specialized for processing the CF-signal range (76 kHz and higher). Using conventional transmission electron microscopy and postembedding immunocytochemistry for the inhibitory neurotransmitters GABA and glycine on semithin-alternating sections, we present further evidence that the ventral laminated subdivision of DCN conserves the main elements of microcircuitry and GABA/glycine labeling patterns typical for the mammalian DCN: (i) the main cell types and synaptic inventory of the granule cell/cartwheel cell system of the superficial layers are present as well as (ii) the tuberculoventral cell system of the deep layers. The nonlaminated dorsal subdivision lacks the granule cell/cartwheel cell system and is composed of a mixture of fusiform projection neurons with tuberculoventral cell analogues. Thus the inhibitory tuberculoventral system known to play an important role in temporal and spectral processing in VCN is conserved throughout the DCN of horseshoe bats, whereas functional components of cerebellar-like circuits are reduced in a specialized region that processes the dominant biosonar component. Accepted: 12 January 2001     

Functional organization of the dorsal cochlear nucleus of the horseshoe bat (Rhinolophus rouxi) studied by GABA and glycine immunocytochemistry and electron microscopy.

Unique among mammals, the dorsal cochlear nucleus (DCN) of horseshoe bats consists of two functionally and anatomically distinct subdivisions: a laminated ventral portion that processes the frequency range below the constant frequency (CF) component of the echolocation signal and a nonlaminated dorsal portion that is specialized for processing the CF-signal range (76 kHz and higher). Using conventional transmission electron microscopy and postembedding immunocytochemistry for the inhibitory neurotransmitters GABA and glycine on semithin-alternating sections, we present further evidence that the ventral laminated subdivision of DCN conserves the main elements of microcircuitry and GABA/glycine labeling patterns typical for the mammalian DCN: (i) the main cell types and synaptic inventory of the granule cell/cartwheel cell system of the superficial layers are present as well as (ii) the tuberculoventral cell system of the deep layers. The nonlaminated dorsal subdivision lacks the granule cell/cartwheel cell system and is composed of a mixture of fusiform projection neurons with tuberculoventral cell analogues. Thus the inhibitory tuberculoventral system known to play an important role in temporal and spectral processing in VCN is conserved throughout the DCN of horseshoe bats, whereas functional components of cerebellar-like circuits are reduced in a specialized region that processes the dominant biosonar component.     

Putative inhibitory collicular boutons contact large neurons and their dendrites in the dorsal cochlear nucleus of the rat

Within the circuits of the acoustic nuclei, the inferior colliculus sends descending (collicular) terminals to control with a feedback mechanism, part of the activity of the dorsal cochlear nucleus (DCN). It is not known whether this descending projection is prevalently excitatory or inhibitory. Using the neuronal tracer Wheat Germ Agglutinin conjugated to Horse Radish Peroxidase (WGA-HRP) the connections between the inferior colliculus and the DCN of the rat have been investigated. By far most retrograde labelled large neurons were glycine and GABA negative (pyramidal and giant neurons) and rare medium-size cells were glycine positive. The ultrastructural immunocytochemical analysis for glycine and GABA shows that mainly large, excitatory, neurons innervate the inferior colliculus. Rare medium-size glycine-positive cells with intermediate characteristics between pyramidal and cartwheel cells, seem also to project to the colliculus. Few WGA-HRP labelled boutons contact the large cells or their dendrites, have symmetric pre- and post-synaptic thickenings, contain pleomorphic and/or flat vesicles, and are labelled for GABA or glycine. Since no GABA labelled cells in both the dorsal and ventral cochlear nucleus were retrograde labelled from the colliculus, the source of these intrinsic anterograde labelled boutons must be external to the cochlear nucleus. GABA positive neurons are both present in the inferior colliculus (injected with the tracer) and superior olivary complex (not injected with the tracer). This suggests that the double labelled boutons (WGA-HRP and GABA) are inhibitory GABA-ergic collicular terminals contacting the excitatory neurons of the DCN. Other few boutons or mossy fibers containing round vesicles and immunonegative for both glycine and GABA, were also seen contacting the large neurons and their dendrites in the DCN. As the round vesicles boutons may be derived from other retrograde cells of the cochlear nucleus (pyramidal and stellate cells) and those glycine positive from the glycinergic neurons in paraolivary nuclei, it is more likely that only the WGA-HRP and GABA labelled boutons are true collicular terminals.     

Age-related increase in PKC gamma expression in the cochlear nucleus of hearing impaired C57BL/6J and BALB/c mice

Age-dependent alteration in cellular signaling is implicated in the onset of age-related hearing loss (presbycusis). The gamma subtype of protein kinase C (PKCγ) is a PKC isoenzyme exclusively expressed in central nervous system but its potential role in the presbycusis remains unclear. Using two presbycusis-like animal models (C57BL/6J strain and BALB/c strain), the auditory thresholds were assessed by auditory brainstem response (ABR) in young (2-month-old), adult (8-month-old) and old (24-month-old) groups, and the localization and expression of PKCγ in the cochlear nucleus (CN) was examined by immunohistochemistry, Western blotting and Real-Time PCR. The results showed that PKCγ immmunoreactive (-ir) neurons were mainly concentrated in the molecular layer and fusiform layer of the dorsal CN (DCN) and their number was increased significantly with aging (p<0.05). Moreover, compared with 2-month-old mice, PKCγ expression in the CN at both protein and mRNA levels was significantly increased in the 8-month-old mice and 24-month-old mice (p<0.05). Thus our findings demonstrate a potential link between the increased PKCγ expression and the age-related hearing loss in these mice, suggesting novel strategies for the prevention and therapy of age-associated auditory disorders.     

Directionality derived from pinna-cue spectral notches in cat dorsal cochlear nucleus

We tested two hypotheses to determine whether dorsal cochlear nucleus (DCN) neurons are specialized to derive directionality from spectral notches: DCN neurons exhibit greater spectral-dependent directionality than ventral cochlear nucleus (VCN) neurons, and spectral-dependent directionality depends on response minima (nulls) produced by coincidence of best frequency (BF) and spectral-notch center frequency. Single-unit responses to 50-ms noise and tone bursts were recorded in barbiturate-anesthetized cats (BFs: 4-37 kHz). Units were classified using BF tone poststimulus time histograms. Pauser, onset-G (type II interneurons), and some chopper units were recorded from the DCN. Primary-like, onset-CIL (onset other than onset-G), and most choppers in the sample were recorded from the VCN. Many pauser and onset-G units were highly directional to noise. Chopper, onset-CIL, and primary-like units (collectively referred to as C-O-P units) were not. The difference in directionality depends on a monaural mechanism as pausers were more directional to monaural noise than C-O-P units. Contralateral inhibition produced a small increase in pauser directionality to noise simulation but had no effect on directionality of C-O-P units. Pauser and C-O-P units exhibited similar low directionality to BF tone, showing that the difference in noise directionality between groups depends on spectral cues. These results show that spectral-dependent directionality is a DCN specialization. Azimuth functions of highly directional units exhibited response nulls, and there was a linear relationship between BFs in the range of 8-13 kHz and azimuthal locations of nulls. This relationship parallels the known spatial distribution of spectral-notch center frequencies on the horizontal plane. Furthermore spatial receptive fields of pausers show response nulls that follow the expected diagonal trajectory of the spectral notch in this frequency range. These results show that DCN spectral-dependent directionality depends on response nulls produced by coincidence of unit BF and spectral-notch center-frequency.     

Age-related increases in calcium-binding protein immunoreactivity in the cochlear nucleus of hearing impaired C57BL/6J mice

Aging C57BL/6J (C57) mice (1-30 months old), were used to study calcium-binding protein immunoreactivity (parvalbumin, calbindin and calretinin) in the cochlear nucleus. A quantitative stereological method, the optical fractionator was used to determine the total number of neurons, and the total number of immunostained neurons in the posteroventral- and dorsal cochlear nuclei (PVCN and DCN). A statistically significant age-related decrease of the total number of neurons was found in the PVCN and DCN using Nissl staining. In the DCN, an age-related increase in the total number of parvalbumin-positive neurons was found, while no changes in the total number of calbindin or calretinin positive neurons were demonstrated. In the PVCN, the total number of parvalbumin, calbindin, or calretinin positive neurons remained stable with increasing age. The percentage of parvalbumin, calbindin, and calretinin positive neurons significantly increased in the DCN, and the percentage of parvalbumin and calbindin-positive neurons increased in the PVCN. These findings imply that there is a relative up-regulation of calcium-binding proteins in neurons that had not previously expressed these proteins. This plastic response in the profoundly hearing impaired C57 mouse may be a survival strategy for cochlear nucleus neurons.     

Mossy fibers in granule cell areas of the rat dorsal cochlear nucleus from intrinsic and extrinsic origin innervate unipolar brush cell glomeruli

Non tonotopic transmission between cochlear nuclei and other auditory and non-auditory nuclei in the brain is probably due to large axonal terminals (mossy fibers) innervating granule cell areas of cochlear nuclei. The origin of mossy fibers in the dorsal cochlear nucleus (DCN) is multiple, from other auditory or non-auditory nuclei but possibly also from intrinsic neurons. The present ultrastructural immunocytochemical study reports for the first time the presence of anterograde-labeled mossy fibers in the DCN of the rat after injection of the neural tracer WGA-HRP into 3 different nuclei. Labeled mossy fibers were seen in 9.0% of mossy fibers detected after tracer injection into the ipsilateral anteroventral cochlear nucleus, in 7.3% of mossy fibers after contralateral collicular injection, and 13.2% after contralateral cochlear nucleus injection. Most (over 95%) mossy fibers contained round vesicles, both large and small, and were likely excitatory terminals, but few showed flat-pleomorphic vesicles that contained the inhibitory neurotransmitters GABA and glycine. Most of the anterograde-labeled ipsilateral mossy fibers containing small round synaptic vesicles, are probably derived from multipolar neurons within the ipsilateral anteroventral cochlear nucleus. After injections into the contralateral inferior colliculus, it was not possible to distinguish putative descending collicular mossy fibers from intrinsic mossy fibers. The latter would suggest the presence of an amplification pathway within the DCN, from collateral axons of pyramidal or stellate cells of the ipsilateral ventral cochlear nucleus to form glomeruli with granule-unipolar brush cells. After injection into the contralateral cochlear nucleus, it was not possible to distinguish between commissural mossy fibers and those derived from ipsilateral recurrent axon-terminals of commissural neurons within the DCN or the ventral cochlear nucleus. Despite this limitation, the present observations show that extrinsic or intrinsic mossy fibers reach granule cell areas in layers 2 and 3 of the DCN and form glomeruli of large or small dimension (1.5-4 microm) with unipolar brush and granule cells. These mossy fibers probably carry a fast excitatory non-tonotopic input which may influence the electrical response of granule cell areas.     

卡铂诱导的听神经病模型大鼠脑干蜗神经核细胞凋亡因子的表达变化

目的 探讨卡铂（CBP）诱导的听神经病模型大鼠脑干蜗神经核细胞凋亡倾向及地塞米松（DEX）的神经保护作用。 方法 采用腹腔注射CBP制作听神经病模型。将SD大鼠随机分为3组,即生理盐水组（NS）、卡铂组（CBP）、地塞米松干预+卡铂组（DEX+CBP）,每组18只,并设3d及6d时间观察点。应用免疫组织化学方法观察各组大鼠脑干蜗神经核Caspase-3免疫反应性;RT-PCR技术检测凋亡酶激活因子1（Apaf-1） mRNA含量。结果 在3d及6d时间点,CBP组大鼠脑干蜗神经核腹侧核（VCN）及背侧核（DCN）Caspase-3免疫反应性及Apaf-1 mRNA含量明显强于NS组及DEX+CBP组（P＜0.05）,DEX+CBP组脑干蜗神经核VCN及DCN内Caspase-3免疫反应性及Apaf-1 mRNA含量与NS组差异无显著性（P＞0.05）。而6d时间点CBP组蜗神经核Apaf-1 mRNA含量显示强于3d时间点。结论 卡铂诱导听神经损伤的同时,也可引起大鼠脑干蜗神经核细胞凋亡倾向,而地塞米松具有神经保护作用,减弱上述的凋亡效应。
     

Effects of contralateral sound stimulation on unit activity of ventral cochlear nucleus neurons

The cochlear nucleus (CN) commissural connection represents the first opportunity for convergence of binaural information in the auditory brainstem. All major neuron types in the ventral CN (VCN) are innervated by a diverse population of cells in the contralateral VCN. This study examined the effect of contralateral sound stimulation on the spontaneous rates (SRs) of neurons in the VCN. Unit activity was recorded with silicon-substrate multichannel probes which allowed recordings from up to 16 sites simultaneously. On average, 30% of units showed short-latency (often only 2 ms greater than the latencies of ipsilateral sound-evoked responses) inhibition of SR by wideband contralateral noise bursts. Fewer units (4.5%) were excited by contralateral noise at sound levels low enough to exclude excitation by acoustic crossover. Both regular and irregular units in the anterior VCN (AVCN) and posterior VCN (PVCN) were inhibited by contralateral sound. Decrements in SR followed a monotonic function with increases in contralateral sound level, except where responses could be attributed to acoustic crossover. Restricting the contralateral noise bandwidth resulted in a frequency-specific inhibition, dominated by frequencies at and below the ipsilateral BF of the unit, consistent with anatomical findings of the tonotopic organization of the CN commissural pathway. The latencies of these effects are compatible with mono, di and tri-synaptic connections reflecting CN commissural pathway effects.     

Expression of GABA(A) receptor subunits in rat brainstem auditory pathways: cochlear nuclei, superior olivary complex and nucleus of the lateral lemniscus

Inhibition by GABA is important for auditory processing, but any adaptations of the ionotropic type A receptors are unknown. Here we describe, using in situ hybridization, the subunit expression patterns of GABA(A) receptors in the rat cochlear nucleus, superior olivary complex, and dorsal and ventral nuclei of the lateral lemniscus. All neurons express the beta3 and gamma2L subunit messenger RNAs, but use different alpha subunits. In the dorsal cochlear nucleus, fusiform (pyramidal) and giant cells express alpha1, alpha3, beta3 and gamma2L. Dorsal cochlear nucleus interneurons, particularly vertical or tuberculoventral cells and cartwheel cells, express alpha3, beta3 and gamma2L. In the ventral cochlear nucleus, octopus cells express alpha1, beta3, gamma2L and delta. Spherical cells express alpha1, alpha3, alpha5, beta3 and gamma2L. In the superior olivary complex, the expression profile is alpha3, alpha5, beta3 and gamma2L. Both dorsal and ventral cochlear nucleus granule cells express alpha1, alpha6, beta3 and gamma2L; unlike their cerebellar granule cell counterparts, they do not express beta2, gamma2S or the delta subunit genes. The delta subunit's absence from cochlear nucleus granule cells may mean that tonic inhibition mediated by extrasynaptic GABA(A) receptors is less important for this cell type. In both the dorsal and ventral nuclei of the lateral lemniscus, alpha1, beta3 and gamma2L are the main subunit messenger RNAs; the ventral nucleus also expresses the delta subunit. We have mapped, using in situ hybridization, the subunit expression patterns of the GABA(A) receptor in the auditory brainstem nuclei. In contrast to many brain regions, the beta2 subunit gene and gamma2S splice forms are not highly expressed in auditory brainstem nuclei. GABA(A) receptors containing beta3 and gamma2L may be particularly well suited to auditory processing, possibly because of the unique phosphorylation profile of this subunit combination.     

Anatomy of the cochlear nuclear complex of guinea pig

Summary The cyto-and fibre-architecture of the cochlear nuclear complex of the guinea-pig has been studied in serial sections using Nissl, Golgi and combined cellmyelin staining of normal material, and a silver degeneration method after cochlear ablation. The nuclear subdivisions and major cell types can be recognised on the basis of those found in the cat, but there are some differences between the two species in the precise distribution and morphology of the neurons. The rostrodorsal part of the anteroventral cochlear nucleus (AVCN) contains predominantly spherical bushy cells, but these cannot be readily divided into large and small types as in the cat. Globular bushy cells are seen in the caudal region of the AVCN, but the majority occur in the posteroventral cochlear nucleus (PVCN), in an area extending from the nerve root right up to the boundary of the dorsal cochlear nucleus (DCN). The octopus cells constitute a distinct region in the most dorsomedial part of the PVCN underneath the DCN. Giant cells are seen scattered around the nerve root region. Multipolar and small cells are seen throughout the non-granular regions of the ventral cochlear nucleus (VCN) except for the octopus cell area, but occur mainly in the more rostral regions of the PVCN. Small cells occur in greatest abundance in the thin cap area at the dorsal edge of the VCN below a superficial granule cell layer. The latter covers the dorsolateral surface of the VCN, and a lamina of granule cells partially separates the PVCN from the DCN. The DCN can be divided into four layers. The outermost molecular layer (layer 1) is separated from the deeper regions by a prominent layer of granule cells (layer 2) which also contains the pyramidal cells. Molecular layer stellate cells are seen in layer 1 and a staggered row of cartwheel neurons is found at the boundary between layers 1 and 2. Layer 3 contains the basal dendrites of the pyramidal cells and some small (vertical) cells, and is innervated by the descending branches of the cochlear nerve. The deepest layer 4, which contains multipolar cells and giant cells, does not appear to receive this direct cochlear input.Abbreviations ab ascending branches of cochlear nerve fibres - AVCN anteroventral cochlear nucleus - BIC brachium of the inferior colliculus - BP brachium pontis - C caudal - cap cap area - Cb cerebellum - Cbgr cerebellar granule cells - CNC cochlear nuclear complex - Co cochlea - CoN cochlear nerve - Cp cerebellar peduncles - Cx cerebral cortex - D dorsal (for direction), also dorsal acoustic stria - db descending branches of cochlear nerve fibres - DCN dorsal cochlear nucleus - DFT descending fibre tract of Lorente de Nó - DL dorsolateral - ep ependyma - Fl flocculus - g globular cell - gca globular cell area - gr granule cell - I intermediate acoustic stria - IC inferior colliculus - L lateral - lam granule cell lamina - LL lateral lemniscus - LSO lateral nucleus of the superior olivary complex - M medial - m multipolar cell - MGB medial geniculate body - N5 trigeminal nerve - nr cochlear nerve root - oca octopus cell area - P pons - PVCN posteroventral cochlear nucleus - py pyramidal cell - R rostral - RB restiform body - s spherical cell - SC superior colliculus - sca spherical cell area - sgrl superficial granule cell layer - TB trapezoid body - tc taenia choroidea - V ventral - VCN ventral cochlear nucleus - VeN vestibular nerve - VM ventromedial - VTT ventrotubercular tract - IV fourth ventricle - 1–4 layers of DCN     

GABAergic inhibition upon auditory response properties of neurons in the dorsal cochlear nucleus of the rat

Summary It is well known that the superficial layers of the dorsal cochlear nucleus (DCN) are rich in GABAergic neurons. We investigated the effects of topical application of GABA receptor agonists and/or antagonists upon the auditory response properties of DCN neurons in rats anesthetized with alpha chloralose-urethane. Auditory stimuli consisted of 20 ms tone bursts presented in a free field. Response properties of DCN neurons were studied before and during iontophoretic application of GABA, bicuculline methiodide (BIC) and muscimol (MUS) alone and GABA with MUS or BIC through triple barrel electrodes glued to the recording microelectrode. Of 68 DCN neurons studied, 27 were sensitive to topical application of the GABA agonists or antagonist. In these neurons, BIC enhanced spontaneous activity as well as auditory responses and decreased the Q-30 quality factor values. MUS reduced auditory responses. BIC often increased the width of the tuning curve but GABA and/or MUS reduced it. Without drug application, GABA sensitive neurons tended to have longer response latencies and larger tuning widths at 30 dB above threshold as well as larger Q-30 values as compared with neurons that were insensitive to GABA. These findings suggest that: 1) GABAergic neurons determine the width of the tuning curve in neurons with GABA receptors by curtailing the excitatory response area, and 2) such neurons receive tonic inhibition from intrinsic GABAergic neurons.