Cells In Cochlear Nucleus Research Articles

Transient Potassium Currents Regulate the Discharge Patterns of Dorsal Cochlear Nucleus Pyramidal Cells

Pyramidal cells in the dorsal cochlear nucleus (DCN) show three distinct temporal discharge patterns in response to sound: "pauser," "buildup," and "chopper." Similar discharge patterns are seen in vitro and depend on the voltage from which the cell is depolarized. It has been proposed that an inactivating A-type K+ current (IKI) might play a critical role in generating the three different patterns. In this study we examined the characteristics of transient currents in DCN pyramidal cells to evaluate this hypothesis. Morphologically identified pyramidal cells in rat brain slices (P11-P17) exhibited the three voltage-dependent discharge patterns. Two inactivating currents were present in outside-out patches from pyramidal cells: a rapidly inactivating (IKIF, tau approximately 11 msec) current insensitive to block by tetraethylammonium (TEA) and variably blocked by 4-aminopyridine (4-AP) with half-inactivation near -85 mV, and a slowly inactivating TEA- and 4-AP-sensitive current (IKIS, tau approximately 145 msec) with half-inactivation near -35 mV. Recovery from inactivation at 34 degrees C was described by a single exponential with a time constant of 10-30 msec, similar to the rate at which first spike latency increases with the duration of a hyperpolarizing prepulse. Acutely isolated cells also possessed a rapidly activating (<1 msec at 22 degrees C) transient current that activated near -45 mV and showed half-inactivation near -80 mV. A model demonstrated that the deinactivation of IKIF was correlated with the discharge patterns. Overall, the properties of the fast inactivating K+ current were consistent with their proposed role in shaping the discharge pattern of DCN pyramidal cells.

The mechanisms underlying temporal pitch perception studied with sequences of filtered clicks

In order to probe the mechanisms underlying temporal pitch perception it is necessary to eliminate all spectral cues from the stimulus, i.e., to use stimuli that cannot be resolved by the cochlea. High-pass filtered clicks combined with the corresponding low-pass filtered noise prove to be especially suitable for the construction of stimuli with specific temporal properties. These stimuli allow for the testing of specific hypotheses concerning temporal processing in the auditory system. The present study compares psychophysical results, obtained with periodic and aperiodic click sequences with single-cell simulations of chopper cells in the ventral cochlear nucleus. The latter are thought to explain the observed sensitivity to temporal regularity.

Role of acoustic striae in hearing: Reflexive responses to elevated sound-sources

This report is the fourth in a series describing the results of ablation-behavior experiments directed to the ascending output of the cochlear nuclei as it is conducted centrally within the acoustic striae. This fourth report focuses on the unique physiology of the fusiform or ‘output’ cells of the dorsal cochlear nucleus whose axons course through the dorsal acoustic stria (DAS). Because electrophysiological studies have shown that the cues for sensing the elevation of a sound source would seem to be best analyzed by the dorsal cochlear nucleus and projected centrally via its DAS, we tested normal cats and cats deprived of DAS for their ability to orient to elevated sources of broad-band noise. For behavioral testing, we made use of reflexive or unconditioned orienting responses to elevated sound sources using a similar method to one we have used previously for azimuth testing (Thompson GC, Masterton RB. Brainstem auditory pathways involved in reflexive head orientation to sound. J Neurophysiol 1978;41:1183–1202). The results show that cats deprived of their DAS do indeed have a marked deficit in their ability to orient to an elevated sound source. Further behavioral testing indicated that this deficit is not the secondary result of an attentional or peripheral motor deficit. Although the present results do not prove that the reflexive deficit is strictly auditory in nature, the deficit is notable in that it is the only one yet known to result from a lesion of the dorsal cochlear nucleus or its central projections.

Contrasting Ca2+ channel subtypes at cell bodies and synaptic terminals of rat anterioventral cochlear bushy neurones

1. Whole-cell patch clamp recordings were made from bushy cells of the anterioventral cochlear nucleus (aVCN) and their synaptic terminals (calyx of Held) in the medial nucleus of the trapezoid body (MNTB). 2. Both high voltage-activated (HVA) and low voltage-activated (LVA) calcium currents were present in acutely dissociated aVCN neurones and in identified bushy neurones from a cochlear nucleus slice. 3. The transient LVA calcium current activated rapidly on depolarization (half-activation, -59 mV) and inactivated during maintained depolarization (half-inactivation, -89 mV). This T-type current was observed in somatic recordings but was absent from presynaptic terminals. 4. On the basis of their pharmacological sensitivity, P/Q-type Ca2+ channels accounted for only 6 % of the somatic HVA, while L-, N- and R-type Ca2+ channels each accounted for around one-third of the somatic calcium current. 5. The divalent permeabilities of these native calcium channels were compared. The Ba2+/Ca2+ conductance ratios of the somatic HVA and LVA channels were 1.4 and 0.7, respectively. The conductance ratio of the presynaptic HVA current was 0.9, significantly lower that that of the somatic HVA current. 6. We conclude that LVA currents are expressed in the bushy cell body, but are not localized to the excitatory synaptic terminal. All of the HVA current subtypes are expressed in bushy cells, but there is a strong polarity to their localization; P-type contribute little to somatic currents but predominate at the synaptic terminal; L-, N- and R-types dominate at the soma, but contribute negligibly to calcium currents in the terminal.

Ultrastructural and immunocytochemical characterization of commissural neurons in the ventral cochlear nucleus of the rat

Medium to large-giant multipolar neurons in the rat ventral cochlear nucleus were retrograde labelled after injection of the tracer Wheat Germ Agglutinin conjugated to Horse Radish Peroxidase into the contralateral cochlear nucleus. Light microscopy immunocytochemistry showed that 42.45% of these retrograde labelled neurons, generally strongly labelled with the tracer, were markedly glycine immunopositive, and that 57.55%, usually weakly retrograde labelled neurons, were immunonegative or weakly positive for glycine. These commissural neurons were generally GABA negative and variably immunopositive for glutamate. About 1/3rd of the commissural neurons had variably developed a rough endoplasmic reticulum whilst axo-somatic boutons covered 20-40% of the cell body. These cells were recognized as multipolar neurons of type I. Most of them were weakly glycine positive or even negative and a few appeared glycinergic. A little less than the remaining 2/3rds of the whole commissural population in the postero-ventral cochlear nucleus presented a surface which was 65-85% covered with synaptic boutons, among which some also appeared labelled. These cells were recognized as multipolar neurons of type II. Many microtubules and neurofilaments were present, free ribosomes being more numerous around Nissl bodies with short cisternae. A few low retrograde labelled type II were weakly or non glycinergic. A small number of large to giant neurons type II, strongly retrograde labelled, appeared to be glycine positive, consistently GABA negative and variably glutamate positive. A very small proportion of retrograde labelled neurons appeared having the characteristics of globular bushy neurons. Their weak labelling, however, suggests that they project by collaterals or thin axons to the contralateral cochlear nucleus. Spherical bushy cells in the rat anteroventral cochlear nucleus lack the nuclear capping of rough endoplasmic reticulum observed in the cat, and none was labelled after injection into the contralateral cochlear nucleus. Globular and spherical neurons were variably glutamate positive but glycine and GABA negative. In conclusion, the present study suggests that commissural neurons include a small number of strongly labelled large to giant glycinergic and presumably inhibitory type II and, less frequently type I. A large group of less heavily labelled commissural neurons of type I and II contain low levels or no glycine, which is probably used for metabolic purposes rather than as a neurotransmitter. This suggests that these neurons are presumably excitatory.

Facilitation of acoustic responses of cartwheel neurons of the cat dorsal cochlear nucleus.

Responses to clicks were increased in cartwheel cells of the dorsal cochlear nucleus of cats after pairing presentations of the clicks with local iontophoretic delivery of glutamate. The cells were identified by bursting discharges, and were recorded intracellularly in vivo. The findings indicate that inhibitory interneurons such as cartwheel cells can participate in complex adaptive acoustic signal processing. Each cell displayed doublet discharges of > 800 Hz. In 70% of the cells, some of the doublet discharges reached rates > 1000 Hz.

Ultrastructure of neurons and large synaptic terminals in the lateral nucleus of the trapezoid body of the cat.

Neurons of the lateral nucleus of the trapezoid body (LNTB), the most prominent periolivary nucleus of the cat superior olivary complex, form an important component of the descending auditory pathways and also innervate the medial superior olive. Cells forming the posteroventral subnucleus (pvLNTB), when investigated by light microscopy, exhibit morphological similarities with globular bushy cells of the cochlear nucleus and principal cells of the medial nucleus of the trapezoid body. These latter two cell types are integral components of brainstem circuitry mediating the early stages of sound localization. In this report, ultrastructural features of LNTB neurons are described. pvLNTB cell bodies are characterized by a round to oval shape, smooth nuclear membrane, and the relative paucity of stacks of rough endoplasmic reticulum. In addition, pvLNTB cell bodies and proximal dendrites are contacted by large synaptic terminals which contain round synaptic vesicles and form multiple asymmetric synaptic junctions. These ultrastructural characteristics are similar to those previously described for globular and principal cells and distinguish pvLNTB cells from cells of the main subnucleus. Large terminals contacting pvLNTB cells contain a specialized organelle assembly, including an adherens plaque associated by filamentous strands with a mitochondrion. We name this organelle assembly the mitochondria-associated adherens complex (MAC) and note its proximity to synaptic junctions. Because high activity rates are characteristic of large terminals in the lower auditory system, the MAC may play a specialized role in membrane stabilization at synapses which generate high rates of vesicle membrane turnover.

Postnatal development of GABA- and glycine-like immunoreactivity in the cochlear nucleus of the Mongolian gerbil (Meriones unguiculatus).

The maturation of the morphological substrate for inhibitory interactions was investigated in the cochlear nucleus of the gerbil with immunocytochemistry for gamma aminobutyric acid (GABA) and glycine on alternating vibratome sections. The patterns of immunostaining obtained with both antibodies in the adult closely conformed to the general mammalian scheme. Qualitative analyses revealed an age-related increase in staining intensity and in the relative numbers of immunolabelled cells after birth up to the age of 3-4 weeks. As early as birth and in all subdivisions of the cochlear nucleus, a few labelled cells and puncta in the sections were stained either with the GABA or the glycine antibody. Immunoreactive puncta and cells were, however, far less abundant than in the adult, and the staining intensity of cells was only weak. The most strikingly GABA-immunolabelled cells at birth were the Golgi cells of the granule-cell domains. The numbers of weakly GABA- and glycine-immunostained cells of the dorsal cochlear nucleus clearly increased between birth and the third postnatal week. At approximately the onset of hearing (postnatal day 12-14), some cells of the dorsal cochlear nucleus and small cells of the ventral cochlear nucleus gained adult-like GABA-staining properties. Almost adult-like labelling intensity was observed in glycine-immunoreactive cells of the deep dorsal cochlear nucleus and in some small cells of the ventral cochlear nucleus. Puncta staining to both antibodies appeared adult-like throughout the cochlear nucleus. About 2 weeks after the onset of hearing (at the latest), adult-like staining of all subsets of immunoreactive cells occurred throughout the cochlear nucleus in all specimens.

Role of acoustic striae in hearing: discrimination of sound-source elevation

After years of systematic experimentation, we finally uncovered one thing the dorsal system contributes to hearing which the ventral system may not – the mechanism for orienting to an elevated sound source [Sutherland, D.P., Masterton, R.B., Glendenning, K.K. (1998) Behav. Brain Res. in press]. This paper follows up this one positive result on a historical background of uniformly negative results. The focus of this report is on the fusiform cells of the dorsal cochlear nucleus whose axons course through the dorsal acoustic stria (DAS). Because electrophysiological studies have shown that the cues for sensing the elevation of a sound source would seem to be best analyzed by the dorsal cochlear nucleus, we tested, behaviorally, normal cats and cats deprived of their DAS or intermediate acoustic stria, bilaterally or ipsilaterally (with or without their contralateral ear deafened), for their ability to orient to elevated sources of broad-band noise. For behavioral testing, we made use of a conventional shock-avoidance procedure. The results lead to the conclusion that DCN and DAS may play no role in learned elevation discriminations. This result builds on that of another of our papers which suggests that a deficit in reflexive discrimination of elevation is strictly auditory in nature [Sutherland, D.P., Masterton, R.B., Glendenning, K.K. (1998) Behav. Brain Res. in press].

Differential distribution of NMDA receptor subunit mRNA in the rat cochlear nucleus

The distribution and expression of mRNAs for different subunits of the N-methyl-D-aspartate receptor (NMDAR) were examined in the cochlear nucleus (CN) of the rat using radioactive in situ hybridization methods. Heavy labeling for NMDAR1 subunit mRNA was observed in all major CN neuronal types with lower labeling for NMDAR2A, 2B, 2C, and 2D mRNA. Silver grain counting was used to compare expression of different NMDAR2 subunits between six of the major CN cell types. Small cells of the small cell cap/shell area had the highest expression of NMDAR2A–C subunit mRNAs of the cell types assessed. These small cells as well as fusiform and corn cells of the dorsal cochlear nucleus had higher NMDAR2C than other NMDAR2 subunits, providing these neuron types with a distinct expression pattern or profile. The other three cell types assessed, spherical bushy cells, granule cells, and octopus cells had relatively equivalent levels of NMDAR2A–C subunit expressions, providing a second distinct profile. NMDAR2D mRNA had low expression in all six cell types assessed. Microsc. Res. Tech. 41:217–223, 1998. © 1998 Wiley-Liss, Inc.

Differential distribution of NMDA receptor subunit mRNA in the rat cochlear nucleus.

The distribution and expression of mRNAs for different subunits of the N-methyl-D-aspartate receptor (NMDAR) were examined in the cochlear nucleus (CN) of the rat using radioactive in situ hybridization methods. Heavy labeling for NMDAR1 subunit mRNA was observed in all major CN neuronal types with lower labeling for NMDAR2A, 2B, 2C, and 2D mRNA. Silver grain counting was used to compare expression of different NMDAR2 subunits between six of the major CN cell types. Small cells of the small cell cap/shell area had the highest expression of NMDAR2A-C subunit mRNAs of the cell types assessed. These small cells as well as fusiform and corn cells of the dorsal cochlear nucleus had higher NMDAR2C than other NMDAR2 subunits, providing these neuron types with a distinct expression pattern or profile. The other three cell types assessed, spherical bushy cells, granule cells, and octopus cells had relatively equivalent levels of NMDAR2A-C subunit expressions, providing a second distinct profile. NMDAR2D mRNA had low expression in all six cell types assessed.

Differential expression of the metabotropic glutamate receptor mGluR1alpha by neurons and axons in the cochlear nucleus: in situ hybridization and immunohistochemistry.

mGluR1alpha is a metabotropic glutamate receptor involved in synaptic modifiability. A differential expression in specific neuronal types could reflect their different connections and response properties in central auditory processing. Using in situ hybridization and immunohistochemistry, we studied mGluR1alpha receptor expression throughout the cochlear nucleus. Robust labeling occurred in the dorsal cochlear nucleus and small cell shell, with less in the ventral cochlear nucleus. Among the most intensely labeled were the granule cells of the small cell shell. In the dorsal cochlear nucleus, most cell types expressed message and receptor protein, except granule cells. High levels of receptor were expressed by corn cells and cartwheel cells. The terminal dendrites and synaptic spines of cartwheel and fusiform cells contained receptor protein in the molecular layer, where they could synapse with parallel fibers. Fusiform dendrites also expressed mRNA for mGluR1alpha. The basal dendrites of fusiform cells contained receptor protein in the region where they receive cochlear nerve synapses. Immunostaining of terminal axons was prominent in the molecular layer and the small cell shell, where they were associated with synaptic nests, structures thought to provide long-term changes in excitability. Differential expression levels may reflect different functional requirements of specific cell types, including inhibitory interneurons, like corn cells and cartwheel cells, and excitatory interneurons, like granule cells in the small cell shell, which may participate in local circuits involved in modulatory or gating functions, such as stimulus enhancement or suppression. In presynaptic axons, mGluR1alpha may relate to the long-term signaling requirements of their modulatory functions.

Spatiotemporal Tuning of Low-Frequency Cells in the Anteroventral Cochlear Nucleus

Low-frequency cells in the anteroventral cochlear nucleus (AVCN) can be sensitive to changes in the spatiotemporal pattern of discharges across their auditory nerve (AN) inputs (). This sensitivity suggests that these cells may be tuned to particular spatiotemporal patterns, or features, in the discharge patterns of populations of AN fibers. To evaluate and characterize this sensitivity, we developed a technique whereby the physiological responses of AVCN cells to wide-band noise were analyzed using the simulated response of a population of AN fibers to the same noise stimulus. By averaging the simulated two-dimensional spatiotemporal pattern of AN activity that preceded each AVCN discharge, it was possible to derive a two-dimensional reverse-correlation function that characterized the spatiotemporal tuning of each AVCN cell. The derived spatiotemporal tuning pattern represented a feature in the AN population response that was most likely to precede discharges of the AVCN cell. To test the spatiotemporal tuning characterizations, we used these patterns to predict the responses of cells to noise stimuli statistically independent from the stimuli used to characterize the cells. This technique provides a general tool for the study of any neural system that involves the analysis of spatiotemporal input patterns.

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 μM) 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.

Synaptic inputs to stellate cells in the ventral cochlear nucleus.

Auditory information is carried from the cochlear nuclei to the inferior colliculi through six parallel ascending pathways, one of which is through stellate cells of the ventral cochlear nuclei (VCN) through the trapezoid body. To characterize and identify the synaptic influences on T stellate cells, intracellular recordings were made from anatomically identified stellate cells in parasagittal slices of murine cochlear nuclei. Shocks to the auditory nerve consistently evoked five types of synaptic responses in T stellate cells, which reflect sources intrinsic to the cochlear nuclear complex. 1) Monosynaptic excitatory postsynaptic potentials (EPSPs) that were blocked by 6,7-dinitroquinoxaline-2,3-dione (DNQX), an antagonist of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, probably reflected activation by auditory nerve fibers. Electrophysiological estimates indicate that about five auditory nerve fibers converge on one T stellate cell. 2) Disynaptic, glycinergic inhibitory postsynaptic potentials (IPSPs) arise through inhibitory interneurons in the VCN or in the dorsal cochlear nucleus (DCN). 3) Slow depolarizations, the source of which has not been identified, that lasted between 0.2 and 1 s and were blocked by -2-amino-5-phosphonovaleric acid (APV), the N-methyl-D-aspartate (NMDA) receptor antagonist. 4) Rapid, late glutamatergic EPSPs are polysynaptic and may arise from other T stellate cells. 5) Trains of late glycinergic IPSPs after single or repetitive shocks match the responses of D stellate cells, showing that D stellate cells are one source of glycinergic inhibition to T stellate cells. The source of late, polysynaptic EPSPs and IPSPs was assessed electrophysiologically and pharmacologically. Late synaptic responses in T stellate cells were enhanced by repetitive stimulation, indicating that the interneurons from which they arose should fire trains of action potentials in responses to trains of shocks. Late EPSPs and late IPSPs were blocked by APV and enhanced by the removal of Mg2+, indicating that the interneurons were driven at least in part through NMDA receptors. Bicuculline, a gamma-aminobutyric acid-A (GABAA) receptor antagonist, enhanced the late PSPs, indicating that GABAergic inhibition suppresses both the glycinergic interneurons responsible for the trains of IPSPs in T-stellate cells and the interneuron responsible for late EPSPs in T stellate cells. The glycinergic interneurons that mediate the series of IPSPs are intrinsic to the ventral cochlear nucleus because long series of IPSPs were recorded from T stellate cells in slices in which the DCN was removed. These experiments indicate that T stellate cells are a potential source of late EPSPs and that D stellate cells are a potential source for trains of late IPSPs.

A quantitative profile of the synapses on the stellate cell body and axon in the cochlear nucleus of the chinchilla.

One of the most numerous neurons in the cochlear nucleus is the type I stellate cell. Previous attempts to understand the structural basis for its signal coding assumed that integration of synaptic potentials arising from axodendritic synapses should account for the generation of its response properties. However, the present study documents the importance of excitatory and inhibitory types of synapses on the soma and axon. Retrograde transport of cholera toxin B subunit, injected in the inferior colliculus of chinchillas, was used to label exclusively type I stellate cells in the anteroventral cochlear nucleus. The relative distribution of terminal types by vesicle morphology was pleomorphic > large spherical > flattened > smaller spherical. The somatic perimeter covered by endings ranged from almost none to nearly half. More flattened-vesicle terminals contacted somata in the high-frequency than in the low-frequency region. Eight of twenty axons received endings that contained large spherical vesicles and made asymmetric junctions; half of these extensively apposed the initial segment, forming a collar of presumed excitatory input. Thus, type I stellate cells are a heterogeneous group. Inhibitory synapses probably compose the majority of terminals. Some cells receive mostly inhibitory synapses near the presumed site of the spike generator, but others also have a prominent excitatory input. These findings call for a new look at the mechanisms for signal coding in stellate cells in the auditory system in particular and raise issues concerning the stochastic nature of information processing in sensory systems in general.

PEP-19 immunoreactivity in the cochlear nucleus and superior olive of the cat

We applied antiserum to PEP-19, a presumptive calcium-binding polypeptide, to the auditory brainstem of cats to determine whether this antiserum would selectively reveal cochlear nucleus neurons and their projections. We report that the entire populations of ventral cochlear nucleus bushy and multipolar cells, but not octopus cells, express this peptide in their somata and dendrites. Presumed axons of spherical bushy cells located dorsally and thicker globular bushy cell fibers located ventrally in the trapezoid body are immunostained, as are thin fibers presumed to represent the axons of multipolar cells. Large calyceal endings in the medial nucleus of the trapezoid body are densely immunoreactive as are smaller punctate profiles that outline immunonegative neuronal profiles in the medial and lateral superior olives. These features of immunolabeling indicate that PEP-19 is expressed in all neuronal compartments. Within the entire superior olivary complex, relatively few neurons are immunolabeled, and the vast majority of these are found in the periolivary nuclei. There are many more immunostained neurons in lateral than in medial periolivary cell groups, but their combined numbers are dwarfed by the numbers of immunolabeled cells in the ventral cochlear nucleus. The borders of the principal nuclei and some of the periolivary cell groups are well defined by the distribution of PEP-19-immunoreactive fibers and puncta. Since ventral cochlear nucleus bushy cells comprise the predominant input to principal nuclei of the superior olive, and the entire bushy cell population is immunolabeled by PEP-19 antiserum, the numbers and distribution of their inputs can be quantified. In this study we report that immunoreactive puncta apposed to the cell bodies and proximal dendrites of neurons in the medial superior olive occur at a density of 20/100μm2. Moreover, we demonstrate by pre-embedding immunoelectron microscopy that the PEP-19-immunoreactive punctate profiles observed in the medial superior olive by light microscopy represent presynaptic terminal boutons that contain round synaptic vesicles and form asymmetric synaptic junctions, features traditionally associated with excitatory synapses.Thus, this antiserum represents a useful tool for investigating the distribution of ventral cochlear nucleus fibers and synaptic terminals within their target nuclei in the superior olive.

Firing properties of spherical bushy cells in the anteroventral cochlear nucleus of the gerbil

In gerbils, spherical bushy cells (SBCs) encode low frequency sound signals into a temporal firing pattern. To investigate the support for the timing in this temporal code, we characterized the membrane electrical properties of visually identified SBCs in brainstem slices. A brief depolarizing subthreshold transient potential (TP) triggered, with relatively invariant latency, a single spike at the onset of a response to depolarizing current pulses. The activation of a subthreshold Na+-conductance, sensitive to blockade with tetrodotoxin, and a high threshold Ca 2+-conductance, sensitive to blockade with Co 2+ or Cd 2+, accelerated the rising phase and amplified the TP. A K +-conductance, sensitive to blockade by 4-aminopyridine (4-AP, 50 μM), shaped the decay of the TP. Following a single spike, voltage-gated activation of transient and sustained K +-conductances suppressed any tendency to repetitively discharge. A reduction in either K +-conductance due to application of 4-AP or etraethylammonium (TEA, 10 mM), converted the single spike mode to repetitive firing during the depolarizing pulses. A persistent, tetrodotoxin-sensitive Na +-conductance amplified steady-state depolarizing responses. A hyperpolarization-activated conductance, greatly decreased by extracellular Cs + (3 mM) but resistant to Ba 2+ (up to 1 mM), filtered the responses to hyperpolarizing current inputs. A depolarized membrane potential promoted repetitive firing in SBCs. This state, expected in pathophysiological conditions, would corrupt the temporal code.

Membrane currents influencing action potential latency in granule neurons of the rat cochlear nucleus.

Granule cells are the most numerous neurons in the cochlear nucleus, but, because of their small size, little information on their membrane properties and ionic currents is available. We used an in vitro slice preparation of the rat ventral cochlear nucleus to make whole-cell recordings from these cells. Under current clamp, some granule neurons fired spontaneous action potentials and all generated a train of action potentials on depolarization (threshold current, 10-35 pA). Hyperpolarization increased the latency to the first action potential evoked during a subsequent depolarization. We examined which voltage-gated currents might underlie this latency shift. In addition to a fast inward Na+ current, depolarization activated two outward potassium currents. A transient current was rapidly inactivated by membrane potentials positive to -60 mV, while a second, more slowly inactivating current was observed following the decay of the transient current. No hyperpolarization-activated conductances were observed in these cells. Modelling of the currents suggests that removal of inactivation on hyperpolarization accounts for the increased action potential latency in granule cells. Such a mechanism could account for the 'pauser'-type firing patterns of the fusiform cells which receive a prominent projection from the granule cells in the dorsal cochlear nucleus.

Cochlear nucleus cell size changes in the dalmatian: Model of congenital deafness

We assessed cellular changes in one population of neurons of the cochlear nucleus associated with a form of genetic deafness in deaf dalmatians. Spheric cells from deaf dalmatians and age-matched control (hearing) dogs were analyzed morphometrically. The somatic silhouette of these cells was reduced by 22.1% to 38.1%. The effect on cell size was greater with increased duration of deafness. Because the deaf dalmatian exhibits progressive degeneration of the auditory periphery, shrinkage of spheric cells may reflect the initial influence of attenuated activity of auditory nerve fibers, and sensorineural degeneration with longer periods of deafness. (Otolaryngol Head Neck Surg 1997;117:229-35.)