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PubMed2002

Cisplatin-induced hyperactivity in the dorsal cochlear nucleus and its relation to outer hair cell loss: relevance to tinnitus.

Cisplatin causes both acute and chronic forms of tinnitus as well as increases in spontaneous neural activity (hyperactivity) in the dorsal cochlear nucleus (DCN) of hamsters. It has been hypothesized that the induction of hyperactivity in the DCN may be a consequence of cisplatin's effects on cochlear outer hair cells (OHCs); however, systematic studies testing this hypothesis have yet to appear in the literature. In the present investigation, the relationship between hyperactivity and OHC loss, induced by cisplatin, was examined in detail. Hamsters received five treatments of cisplatin at doses ranging from 1.5 to 3 mg. kg(-1). day(-1), every other day. Beginning 1 mo after initiation of treatment, electrophysiological recordings were carried out on the surface of the DCN to measure spontaneous multiunit activity along a set of coordinates spanning the medial-lateral (tonotopic) axis of the DCN. After recordings, cochleas were removed and studied histologically using a scanning electron microscope. The results revealed that cisplatin-treated animals with little or no loss of OHCs displayed levels of activity similar to those seen in saline-treated controls. In contrast, the majority (75%) of cisplatin-treated animals with severe OHC loss displayed well-developed hyperactivity in the DCN. The induced hyperactivity was seen mainly in the medial (high-frequency) half of the DCN of treated animals. This pattern was consistent with the observation that OHC loss was distributed mainly in the basal half of the cochlea. In several of the animals with severe OHC loss and hyperactivity, there was no significant damage to IHC stereocilia nor any observable irregularities of the reticular lamina that might have interfered with normal IHC function. Hyperactivity was also observed in the DCN of animals showing severe losses of OHCs accompanied by damage to IHCs, although the degree of hyperactivity in these animals was less than in animals with severe OHC loss but intact IHCs. These results support the view that loss of OHC function may be a trigger of tinnitus-related hyperactivity in the DCN and suggest that this hyperactivity may be somewhat offset by damage to IHCs.

Action Potentials↗
PubMed2001

Effects of divalent cations on voltage-gated Ca2+ channels and depolarization-induced [Ca2+], transients of freshly isolated pyramidal cells of the rat dorsal cochlear nucleus.

The effects of divalent cations on voltage-activated Ca2+ channels and depolarization-evoked cytoplasmic [Ca2+] elevations were studied in pyramidal neurones isolated from the dorsal cochlear nucleus of the rat. Ca2+ currents were recorded using the whole-cell configuration of the patch-clamp technique. 10 micromol x l(-1) Cd2+ exerted a greater blocking effect on the high-voltage activated (HVA) currents than on the low-voltage activated (LVA) ones (decrease to 26.6+/-2.5% and to 87.8+/-2.1%, respectively). The blocking effect of 200 micromol x l(-1) Cd2+ was more pronounced and the difference between the effect on the HVA and LVA currents became smaller (decrease to 11.7+/-2.1% and to 32.4+/-2.7%, respectively). 200 micromol x l(-1) Ni2+ reduced the LVA component more effectively (to 77.6+/-5.4%) than the HVA one (to 86.9+/-2.6%). Cytoplasmic [Ca2+] changes were measured applying a fluorimetric technique (Fura-2). 10 micromol x l(-1) Cd2+ decreased the peak values of 50 mmol x l(-1) K+ depolarization-induced [Ca2]+i transients to 30.4+/-1.4% while 200 micromol x l(-1) Cd2+ caused a drop to 2.5+/-0.2%. 200 micromol x l(-1) Ni2+ decreased the peak of the transients to 69.6+/-2.9%. Comparison of the blocking effects of divalent cations on Ca2+ currents and [Ca2+]i transients supports further the conclusion that the depolarization-induced [Ca2+]i changes are produced mainly by the activation of the HVA Ca2+ channels.

Animals↗
PubMed1996

Analysis of projections from the cochlear nucleus to the lateral paragigantocellular reticular nucleus in the rat.

Golgi-staining, retrograde and anterograde tract-tracing, and a two-color immunoperoxidase technique have been employed, at the light- and electron-microscopic levels, to analyze the auditory projections from the cochlear nucleus (CN) to the lateral paragigantocellular reticular nucleus (LPGi) in the rat. We have found that the auditory input originates predominantly in the posteroventral and cochlear root nuclei. The auditory axons terminate in the cell-poor, ventral portion of the LPGi, which is strongly invaded by beaded dendritic profiles, originating from parent cell bodies located in the dorsal half of the LPGi. Ultrastructural analysis has revealed that the anterogradely labeled auditory axons form functional synapses preferentially with dendritic shafts. These axo-dendritic contacts are apparently excitatory in nature. By means of a sequential two-color immunoperoxidase staining method, we have further characterized potential postsynaptic neurons in the LPGi. Black-stained auditory fibers intermingle with brown-stained serotonergic or adrenergic neurons. Varicose auditory axons are often closely apposed to immunoreactive dendritic profiles of serotonergic and adrenergic neurons, indicating the presence of possible synaptic contacts of auditory terminal fibers with these transmitter-classified cells. The monosynaptic auditory in- put from the CN may modulate the activity of B3 sero-tonergic and C1 adrenergic cells in the LPGi and may thus induce adaptive changes in response to acoustic stimuli.

Afferent Pathways↗
PubMed1990

Adaptations of synaptic form in an aberrant projection to the avian cochlear nucleus.

Surgical removal of the otocyst in chick embryos induces axons from the contralateral cochlear nucleus (nucleus magnocellularis, NM) to form, in addition to their normal endings in nucleus laminaris (NL), anomalous and persistent functional contacts in the ipsilateral NM (Jackson and Parks, 1988). We have examined how interaction between the abnormal synaptic partners during development influences the form of the axon terminal and its relation to the target neuron. In the light microscope, aberrant axon terminals labeled in vitro with HRP appear to form boutons quite unlike the large calycine endbulbs made by the normal cochlear nerve (CN) endings in NM. In the electron microscope, however, the anomalous endings appear embedded in the NM cells, something never seen normally in NM or NL. Morphometric analyses were performed on electron micrographs from NM and NL in animals aged embryonic day (E) 19 to posthatching day (P) 2 from which the right otocyst had been removed on E3 and in normal control animals. Aberrant endings appose 18% of the circumference of operated NM cells, versus 45% for CN axons in the normal NM at this age. The mean length of membrane apposition for the anomalous NM-to-NM endings was 215% greater than for normal NM-to-NL endings but 54% smaller than that in normal CN endings. These results support the idea that developmental interactions between synaptic partners can influence the form of the contact between the 2 neurons. The results also demonstrate, however, that formation of persistent and functional synapses with NM neurons throughout development is not sufficient to induce any axon to assume the calycine form of a cochlear nerve endbulb.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1995

Glutamate is concentrated in and released from parallel fiber terminals in the dorsal cochlear nucleus: a quantitative immunocytochemical analysis in guinea pig.

The present paper addresses the identity of the neurotransmitter(s) of the parallel fibers in the molecular layer of the dorsal cochlear nucleus, a brainstem center in the pathway for sound perception. The distribution of putative neurotransmitter amino acids was studied by using postembedding single- and double-immunolabeling procedures. Perfusion-fixed brains and immersion-fixed slices from in vitro release experiments were evaluated. Quantitative immunogold analyses revealed that the parallel fiber terminals were significantly enriched with glutamate immunoreactivity compared with other terminals, dendrites, and glial processes. Within the parallel fiber terminals, the gold particles signaling the presence of glutamate were concentrated over vesicle clusters relative to the axoplasmic matrix. Furthermore, the parallel fiber terminals, but not the parent granule cell bodies, could be depleted of glutamate immunoreactivity by exposure to depolarizing concentrations of K+ in vitro. This depletion was partly dependent on Ca2+. In double-labeled preparations, the glutamine:glutamate ratio was by far higher in glial processes than in other types of profile. Aspartate immunoreactivity was mainly concentrated in neuronal cell bodies and dendrites and was very low in fiber terminals, particularly in those of the parallel fibers. These data indicate that parallel fiber terminals contain a glutamate pool that is associated with synaptic vesicles and that can be subject to release. The glial processes that are found in proximity to the terminals may provide them with the glutamine required for glutamate replenishment. No evidence was found for a neurotransmitter role of aspartate in the parallel fibers.

Animals↗
PubMed2000

Hyperactivity in the dorsal cochlear nucleus after intense sound exposure and its resemblance to tone-evoked activity: a physiological model for tinnitus.

Intense tone exposure induces increased spontaneous activity (hyperactivity) in the dorsal cochlear nucleus (DCN) of hamsters. This increase may represent an important neural correlate of noise-induced tinnitus, a condition in which sound, typically of very high pitch, is perceived in the absence of a corresponding acoustic stimulus. Since high pitch sounds are thought to be represented in central auditory structures by the place of activation across the tonotopic array; it is therefore possible that the high pitch of noise-induced tinnitus occurs because intense sound exposure induces a tonotopic distribution of chronic hyperactivity in the DCN similar to that normally evoked only under conditions of high frequency stimulation. To investigate this possibility we compared this tone-induced hyperactivity with the activity evoked in normal animals by presentation of a tone. This comparison revealed that the activity in the DCN of animals which had been exposed to an intense 10 kHz tone 1 month previously showed a striking similarity to the activity in the DCN of normal animals during presentation of low to moderate level tonal stimuli of the same frequency. In both test conditions similar patterns were seen in the topographic distribution of the increased activity along the tonotopic axis. The magnitude of hyperactivity in exposed animals was similar to the evoked activity in the normal DCN responding to a stimulus at a level of 20 dB SL. These results suggest that the altered DCN following intense tone exposure behaves physiologically as though it is responding to a tone in the absence of a corresponding acoustic stimulus. The relevance of these findings to noise-induced tinnitus and their implications for understanding its underlying mechanisms are discussed.

Acoustic Stimulation↗
PubMed1995

Development of ectopic projections from the ventral cochlear nucleus to the superior olivary complex induced by neonatal ablation of the contralateral cochlea.

The ability of an animal to localize a sound in space requires the precise innervation of the superior olivary complex by the ventral cochlear nuclei on each side of the lower brainstem. This precise pattern of innervation could require an immutable recognition of appropriate targets by afferent processes arising from these nuclei. This possibility was investigated by destroying one cochlea of gerbil pups (Meriones unguiculatus) on the second postnatal day and assessing the projections from the ventral cochlear nucleus (VCN) on the unablated side to the superior olivary complex during the subsequent 2 weeks and after the animals had reached maturity. A crystal of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) was inserted into VCN on the unablated side in animals ranging in age from 3 to 14 days. To assess the permanence of any altered pattern of innervation, horseradish peroxidase was injected into VCN on the unablated side in adult, neonatally ablated animals. Finally, electrophysiological responses to acoustic stimuli delivered to the ear on the unablated side were recorded in the superior olivary complex of adult animals to assess whether altered innervation patterns were functional. Normative data were derived from our accompanying study of the development of VCN projections to the superior olivary complex in normal gerbils (Kil et al., this issue). Whereas VCN normally projects to the lateral aspect of the ipsilateral medial superior olive and to the medial aspect of the contralateral medial superior olive in control animals, in experimental animals VCN on the unablated side projects to both sides of these nuclei. Whereas in the gerbil, VCN normally projects only to the hilar area and to the ventrolateral limb of the contralateral lateral superior olive, in experimental animals VCN on the unablated side projects throughout this nucleus. This induced projection is specific in that the efferents to each limb of the contralateral nucleus are linked to the normal projection to the homotopic region of the ipsilateral nucleus. Whereas VCN innervates the contralateral medial nucleus of the trapezoid body in control animals, in experimental animals VCN on the unablated side provides calyces of Held in the ipsilateral nucleus as well. The induced projections to these three major subnuclei of the superior olivary complex first appear within 24 hours of the cochlear ablation and continue to develop over at least the subsequent 11 days. Thus, prior to the day when the cochlea becomes functional, VCN has established specific ectopic projections to loci normally innervated by VCN on the ablated side.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗
PubMed1992

Morphology of the dorsal cochlear nucleus in C57BL/6J and CBA/J mice across the life span.

The morphology of the dorsal cochlear nucleus (DCN) was evaluated across the life span in inbred C57BL/6J (C57) and CBA/J (CBA) mice using 5 age groups (young adult to very old). C57 mice exhibit progressive cochlear sensorineural pathology and hearing loss during middle age; CBA mice have only modest sensorineural pathology late in life. DCN layers I, II, and III were evaluated histologically with serial sections stained for Nissl and fibers. DCN volume decreased with age in C57 mice, but the change began earliest and was most pronounced in layer III. In CBA mice, volume increased during the first year of life and decreased only in the oldest mice. All major DCN cell types were found in both strains at all ages. There was an age-related decrease in the mean size of neurons in C57 mice that was first observed in layer III. In CBA mice, only a nonsignificant trend toward smaller neurons was observed in the oldest mice. An age-related decline in the number of neurons in layer III (but not in layers I and II) occurred in C57 mice. Aged CBA mice exhibited no significant loss of DCN neurons. Thus, age-related changes in the DCN were much more pronounced in C57 mice than in CBA mice, and the changes in C57 mice were most pronounced in layer III. Because layer III receives most of the DCN's primary auditory input, it would be directly affected by age-related hearing loss and degeneration of spiral ganglion cells in C57 mice. This suggests that the age-related changes observed in DCN layer III of C57 mice are affected by progressive peripheral degenerative changes; when peripheral loss is minimal (CBA mice), less substantial age-related changes are observed.

Aging↗
PubMed1984

Cartwheel neurons of the dorsal cochlear nucleus: a Golgi-electron microscopic study in rat.

Cartwheel neurons in rat dorsal cochlear nucleus (DCN) were studied by Golgi impregnation-electron microscopy. Usually situated in layers 1-2, cartwheel neurons (10-14 micrometers in mean cell body diameter) have dendritic trees predominantly in layer 1. The dendrites branch at wide angles. Most primary dendrites are short, nontapering, and bear only a few sessile spines. Secondary and tertiary dendrites are short, curved, and spine-laden. The perikaryon forms symmetric synapses with at least two kinds of boutons containing pleomorphic vesicles. The euchromatic nucleus is indented and has an eccentric nucleolus. The cytoplasm shows several small Nissl bodies, a conspicuous Golgi apparatus, and numerous subsurface and cytoplasmic cisterns of endoplasmic reticulum with a narrow lumen, joined by mitochondria in single or multiple assemblies. In primary dendrites mitochondria are situated peripherally, while in distal branches they become ubiquitous and relatively more numerous. Dendritic shafts usually form symmetric synapses with boutons that contain pleomorphic vesicles. The majority of the dendritic spines are provided with a vesiculo-saccular spine apparatus. All dendritic spines have asymmetric synapses. Most of these are formed with varicosities of thin, unmyelinated fibers (presumably axons of granule cells) running parallel to the long axis of the DCN or radially. These varicosities contain round, clear synaptic vesicles. On the initial axon segment few symmetric synapses are present. The axon acquires a thin myelin sheath after a short trajectory. Cartwheel neurons outnumber all other neurons in layers 1-2 (with the exception of granule cells), and presumably correspond to type C cells with thinly myelinated axons described by Lorente de Nó. The axons of these neurons provide a dense plexus in the superficial layers without leaving the DCN. The possible functional role of cartwheel neurons is discussed.

Animals↗
PubMed1990

Responses of single units in the anteroventral cochlear nucleus of the guinea pig.

Single unit responses have been recorded from the anteroventral cochlear nucleus of the anaesthetised guinea-pig. For each unit a response profile was obtained consisting of spike waveform shape, suprathreshold post-stimulus time histogram at characteristic frequency, frequency/intensity response area, a measure of phase-locking and where possible variation in post-stimulus time histogram shape as a function of position within the response area. Units were classified according to schemes based on both post-stimulus time histogram shape and response area. The majority of units with Type I response areas were primarylike and most with Type III response areas were choppers. One-to-one correspondence between the two classification schemes was found for units which were classified as onset by the post-stimulus time histogram scheme and Type I/III by the response area scheme. Primarylike units with a prepotential in their spike waveform most faithfully preserved the temporal information (as measured by phase-locking) present in the auditory nerve input. Primarylike units in which a prepotential was not detected showed varying abilities to phase-lock. Non-primarylike units do not phase-lock as well as auditory nerve fibres in the same species. Nonmonotonic rate-level functions for tones at characteristic frequency were observed across all unit types (with the exception of onset units) classified by the post-stimulus time histogram scheme. An unexpected finding was a small number of primarylike units characterised by reduced driven discharge rates within their response areas. We hypothesize that the mechanism for this reduction is centre-band inhibition.

Acoustic Stimulation↗
PubMedDate not supplied

Matching the neural adaptation in the rat ventral cochlear nucleus produced by artificial (electric) and acoustic stimulation of the cochlea.

To investigate neural adaptive properties, near-field evoked potentials were recorded from a chronically implanted electrode in the ventral cochlear nucleus in awake Long-Evans rats exposed to acoustic stimuli or receiving intracochlear electric stimulation. Stimuli were 250-ms trains of repetitive acoustic clicks (10, 30 and 50 dB SPL) or biphasic electric pulses (30, 50 and 70 microA) with intratrain pulse rates ranging from 100 to 1000 pulses per second (pps). The amplitude of the first negative (N(1)) to positive (P(1)) component of the average evoked potentials was measured for each consecutive individual pulse in the train. While a progressive exponential decrease in N(1)-P(1) amplitude was observed as a function of the position of the pulse within the train for both types of stimulation, the decrement of electric responses (adaptive pattern) was substantially less prominent than that observed for acoustic stimuli. Based on this difference, the present work was extended by modifying electric stimuli in order to try to restore normal adaptation phenomena. The results suggest the feasibility of mimicking acoustic adaptation by stimulation with exponentially decreasing electric pulse trains, which may be clinically applicable in the auditory implant field.

Acoustic Stimulation↗
PubMed1998

Effects of endogenous acetylcholine on spontaneous activity in rat dorsal cochlear nucleus slices.

We have examined the contribution of endogenous acetylcholine (ACh) release to the spontaneous firing of both regular (probably fusiform cells) and bursting neurons (probably cartwheel cells) in the dorsal cochlear nucleus (DCN) in rat brainstem slices. The muscarinic antagonists atropine, scopolamine, and tropicamide (1-2 microM) caused substantial decreases of firing rates in a majority of the neurons. Reversible acetylcholinesterase (AChE) inhibitors typically caused large transient increases in firing that decayed more slowly than responses to carbachol. The irreversible AChE inhibitor diisopropyl fluorophosphate (DFP) usually caused a sustained increase, with an initial peak followed by a gradual change to a final level higher than before DFP. Tropicamide caused large decreases in firing after DFP, confirming sustained ACh release. Both neostigmine and DFP applied after AChE inhibition by DFP sometimes elicited a transient response. We conclude that the level of sustained response to DFP is determined by the rate of endogenous ACh release, and that DFP and reversible AChE inhibitors exert an initial transient agonist effect that overlaps the initial effect of acetylcholinesterase inhibition. The slice experiments provide a model for cholinergic mechanisms in vivo, confirm that the release of endogenous ACh increases the firing rates of regular and bursting neurons in superficial DCN, and support the hypothesis that spontaneous firing of DCN neurons is sustained in part by cholinergic inputs.

Acetylcholine↗
PubMed1989

Classification of unit types in the anteroventral cochlear nucleus: PST histograms and regularity analysis.

1. The responses of neurons in the anteroventral cochlear nucleus (AVCN) of barbiturate-anesthetized cats are characterized with regard to features of their responses to short tone bursts (STBs; 25 ms). A "decision tree" is presented to partition AVCN units on the basis of post-stimulus time histogram (PSTH) shape, first spike latency, and discharge rate and regularity calculated as functions of time during responses to STBs. The major classes of AVCN units (primary-like, primary-like-with-notch, chopper, and onset) have been described previously; in this paper, special attention is given to clarifying and systematizing boundaries between classes. Certain types of "unusual" units that may be confused with units in one of the major classes are also examined. 2. When STBs are presented synchronously (constant phase at onset), PSTHs of responses to very-low-frequency (less than 1.0 kHz) tones are difficult if not impossible to resolve into the classes listed above because all unit types phase-lock to low-frequency tones. However, when STBs are presented asynchronously, the responses of units with low best frequencies can be categorized on the basis of PSTH shape and first spike latency. 3. Primary-like, primary-like-with-notch, and onset units are distinguished primarily on the basis of PSTH shape. These three unit types have comparable minimum first spke latencies and synchronization to tones. One type of "unusual" response poses a particular hazard with respect to the generation of uncontaminated primary-like populations. Such "unusual" units have PSTHs that appear primary-like; these units are, however, distinguished by their unusually long first spike latencies. Unlike primary-like units, these "unusual" units show extremely poor synchronization to tones. 4. Chopper units are defined as having an initial response that is highly regular, resulting in the characteristic multimodal PSTH. "Unusual" units with multimodal PSTHs but whose initial responses are not highly regular (measured by the reproducibility of the initial firing pattern in response to multiple repetitions of a STB) are eliminated from the chopper populations. 5. In barbiturate-anesthetized cats, at least three patterns of chopper response can be distinguished on the basis of temporal patterns of rate and regularity adaptation. "Sustained" choppers show no adaptation of instantaneous rate (measured by the inverse of the mean interspike interval), and their discharge remains highly regular throughout the response. "Transiently adapting" choppers undergo a very rapid (less than 10 ms) decrease in instantaneous rate accompanied by a sharp increase in discharge irregularity.(ABSTRACT TRUNCATED AT 400 WORDS)

Acoustic Stimulation↗
PubMed2000

Differential postsynaptic distribution of GluRs 1-4 on cartwheel and octopus cell somata in the gerbil cochlear nucleus.

Differences were demonstrated in the distribution of glutamate receptors (GluR) 1, 2, 2/3 and 4 postsynaptic immunoreactivity (PSIR) on the somata of cartwheel and octopus cells in the adult gerbil cochlear nucleus (CN). Montages of electron micrographs of cartwheel and octopus cells immunoreacted with antibodies to GluR 1, 2, 2/3 and 4 were prepared. The number of synaptic terminals with PSIR were counted on all cells for each antibody, normalized to the total length of somatic surface analyzed. The density of terminals apposed to PSIR on octopus cells was similar for the antibodies GluR1, 2/3 and 4, but significantly less for GluR2. On cartwheel somata the numbers of terminals apposed to immunoreactive postsynaptic specializations with GluR1, 2, 2/3 or 4 were not significantly different from each other. The density of terminals apposed to GluR2/3 and 4 positive postsynaptic specializations was significantly less on cartwheel cells than on octopus somata. The data suggest that the decreased presence of the GluR2 subunit, which confers calcium impermeability to the assembled receptor and slower gating kinetics to receptors with a high GluR4 content, is the major difference in the AMPA receptors on the somata of these cell types. The presence on cartwheel cells of a majority of AMPA receptors which contain GluR2 may account for the fact that cartwheel cells respond to shocks to the auditory nerve with 100 ms excitatory postsynaptic potentials (EPSPs), while octopus cells, most of whose AMPA receptors lack GluR2, respond with 1 ms EPSPs.

Animals↗
PubMed1991

Posteroventral cochlear nucleus projections to olivocochlear neurons.

The presence of ascending auditory inputs from the posteroventral cochlear nucleus (PVCN) to olivocochlear neurons was examined in guinea pig by using the combination Phaseolus vulgaris-leucoagglutinin (PHA-L) anterograde and horseradish peroxidase (HRP) retrograde tract-tracing technique. By labeling the somata of olivocochlear neurons after injection of HRP into the cochlea and simultaneously labeling terminal endings of PVCN efferent neurons after injection of PHA-L into PVCN, we observed neuronal connections between these two elements within all regions of the superior olivary complex known to contain olivocochlear neurons. These regions include the superior paraolivary nucleus, medial nucleus of the trapezoid body, lateral superior olive, and periolivary regions. All possible projection patterns regarding side of input and output of both large (four combinations) and small (two combinations) olivocochlear neurons were observed. However, the most frequently observed pattern was the PVCN projection to a contralaterally located and contralaterally projecting, large olivocochlear neuron. Thus the most prevalent pattern demonstrated a feedback pathway that crossed the brainstem twice. Additional patterns demonstrated pathways that fed back to the same cochlea as well as pathways that fed forward to the opposite cochlea.

Animals↗
PubMed1990

Recovery from short-term adaptation in single neurons in the cochlear nucleus.

Recovery from short-term adaptation was measured in single neurons in the cochlear nucleus using a forward masking stimulus paradigm. The response to a short-duration, low-level probe tone at a unit's characteristic frequency (CF) was measured before and after presentation of a masker tone at the unit's CF. The degree of adaptation was defined as the ratio of firing to the probe in the adapted and unadapted conditions. The level of the masker and time difference between the masker offset and probe onset ('DT') were varied. As DT increased, the response to the probe increased in most Primarylike, Primarylike-notch, and Chopper units. Recovery was approximately linear in log time for most of these units. However, approximately half the Pauser/Buildup and On units showed very different recovery patterns, ranging from no adaptation to very non-linear recovery patterns. The results suggest that little alteration in the recovery process occurs between the auditory nerve and Primarylike, Primarylike-notch, and Chopper units, but that significant changes in the recovery process occur in Pauser-Buildup and On units.

Acoustic Stimulation↗
PubMed1997

Membrane properties of mouse dorsal cochlear nucleus neurons in vitro.

Intracellular recordings were made from neurons of the mouse dorsal cochlear nucleus (DCN) in vitro using current clamp techniques in the presence or absence of different ion channel blocking drugs. Four electrophysiologically distinct cell groups were identified in the DCN. The groups were characterized on the basis of their spontaneous firing properties, the shape of the action potential (AP) and the pattern of firing, the shape of the current-voltage (I/V) relationship and the effects of channel blocking agents. By comparison with known histology, three of the four DCN groups were postulated to be cartwheel-like, fusiform-like, or tuberculoventral-like cells. The fourth group was postulated to be a stellate-like as it had similar properties to the spike train (stellate) cell of the AVCN. DCN stellate-like cells were spontaneously active, the action potentials (APs) were always followed by a large, brief hyperpolarization and the cells had linear current voltage relationships. The fusiform-like cells were spontaneously active and spontaneous IPSPs were also observed. The I/V relationship was linear for these cells. Tuberculoventral-like cells were not spontaneously active, but APs could be elicited by inward current injection. The I/V relationships for tuberculoventral-like cells were linear. Cartwheel-like cells were spontaneously active. These cells were characterized by the distinctive shape of their APs which were single, large amplitude, short duration APs sometimes followed by a series of complexes consisting of small, long duration APs. Cartwheel-like cells were the only cell type in the DCN which had non-linear I/V relationships. All cells in the DCN had APs which were abolished by tetrodotoxin. Different calcium dependent channels play a role in the formation of both the fast single AP and the slow complex AP in the cartwheel-like cells since all APs were abolished by the use of high concentrations of verapamil. Verapamil dramatically increased the duration of APs in fusiform-like cells and had no effect on tuberculoventral-like cells. In both tuberculoventral-like cells and cartwheel-like cells, 4-aminopyridine (4AP) depolarized the cells and all APs were abolished. Tetraethylammonium chloride (TEA) had a similar effect in cartwheel-like cells. In stellate-like, tuberculoventral-like and fusiform-like cells, the hyperpolarization which followed the AP was abolished by TEA. The AP duration in these cells was also increased by TEA. 4AP had a similar effect in stellate-like and fusiform-like cells. The data for DCN suggest that electrophysiological properties can be used to distinguish and identify neurons.

Action Potentials↗
PubMed1999

Organization of the disynaptic pathway from the anteroventral cochlear nucleus to the lateral superior olivary nucleus in the ferret.

The medial nucleus of the trapezoid body (MNTB) is one of three major nuclei of the superior olivary complex and provides an important inhibitory input from the contralateral ear to the lateral superior olivary nucleus (LSO) in the initial binaural pathway for coding interaural intensity differences. The major input to the MNTB from the contralateral anteroventral cochlear nucleus (AVCN) involves giant, calyx-like endings that have a one-to-one relationship with cells in the MNTB as confirmed in the ferret in this study. The main objective of the present study was to define the subsequent organization of projections from cells receiving these calyx-like endings. Several anatomical tracers (Phaseolus vulgaris leucoagglutinin, dextran-biotin, and biocytin) were used that are transported both anterogradely and retrogradely within neuronal projections in order to define the organization of MNTB connections with the LSO in the adult ferret. Analysis focused on determining the topography in both the transverse and longitudinal planes of the projections. Focal tracer injections in the LSO resulted in retrograde labeling of a long, narrow column of cells in the MNTB. The orientation and location of labeled cells was dependent on the medial-lateral position of the injection site. In the rostral-caudal dimension of MNTB, there was no such topographic relation between the injection site and the position of labeled cells. Labeled cells in the MNTB were distributed more or less evenly in a longitudinal column regardless of whether the injection site was restricted to the rostral, middle or caudal part of the LSO. In keeping with this pattern, tracer injections in the MNTB resulted in bands of labeled axons that distributed endings throughout the rostral-caudal axis of the LSO. These bands or sheets varied in medial-lateral position relative to the location of the injection site, but lacked any such rostral-caudal gradient. Thus, overall the MNTB-LSO projections have a convergent-divergent pattern of organization. While MNTB cells receive singular calyx-like endings from the AVCN, LSO cells receive projections from a long column of cells in the MNTB. Implications for processing interaural intensity differences are discussed.

Animals↗