Bushy Cells Research Articles

Modeling the precedence effect in inferior colliculus neurons using converging excitatory and inhibitory inputs

Responses of a population model of low‐frequency inferior colliculus (IC) neurons to a pair of broadband clicks were evaluated. IC inputs came from Hodgkin‐Huxley models of medial superior olive (MSO) and cochlear nucleus bushy cells driven by a stochastic auditory nerve model. Each IC cell received converging inputs that were excitatory from ipsilateral MSO and inhibitory from contralateral MSO. Convergence of multiple excitatory, ipsilateral MSO inputs with similar interaural time difference (ITD) tuning improved ITD sensitivity and reduced the influence of MSO onset responses caused by monaural, rather than binaural, coincidences. Inhibition that lasted over several milliseconds suppressed IC responses to the lagging click. The effect of the inhibition depended on the ITD tuning of the excitation and inhibition converging on a given IC neuron. With appropriate convergence, the IC population showed no response to the lagging click at short delays, and responded to the lagging click but did not encode its ITD at intermediate delays. Only at longer inter‐click delays did IC responses show sensitivity to the lagging click ITD, consistent with the perceptual phenomenon of the precedence effect. [Work supported by NSF and NIH].

Relative Roles of Different Mechanisms of Depression at the Mouse Endbulb of Held

Several mechanisms can underlie short-term synaptic depression, including vesicle depletion, receptor desensitization, and changes in presynaptic release probability. To determine which mechanisms affect depression under physiological conditions, we studied the synapse formed by auditory nerve fibers onto bushy cells in the anteroventral cochlear nucleus (the "endbulb of Held") using voltage-clamp recordings of brain slices from P15-P21 mice near physiological temperatures. Depression of both alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) excitatory postsynaptic currents (EPSCs) showed two phases of recovery. The fast component of depression for the AMPA EPSC was eliminated by cyclothiazide and aniracetam, suggesting it results from desensitization. The fast component of depression for the NMDA EPSC was reduced by the low-affinity antagonist l-AP5, suggesting it results from saturation. The remaining depression in AMPA and NMDA components is identical and therefore presynaptic in origin. It is likely to result from presynaptic vesicle depletion. Recovery from depression after trains of activity was slowed by the application of EGTA-AM, suggesting that the endbulb has a residual-calcium-dependent form of recovery. We developed a model that incorporates depletion, desensitization, and calcium-dependent recovery. This model replicated experimental findings over a range of experimental conditions. The model further indicated that desensitization plays only a minor role during prolonged activity, in large part because presynaptic release is so depleted. Thus depletion appears to be the dominant mechanism of depression at the endbulb during normal activity. Furthermore, calcium-dependent recovery at the endbulb is critical to prevent complete rundown during high activity and to preserve the reliability of information transmission.

The medial nucleus of the trapezoid body: Comparative physiology

Principal cells of the medial nucleus of the trapezoid body (MNTB) receive their excitatory input through large somatic terminals, the calyces of Held, which arise from axons of globular bushy cells located in the contralateral ventral cochlear nucleus. Discharges of MNTB neurons are characterized by high stimulus evoked firing rates, temporally precise onset responses, and a high degree of phase-locking to either pure tones or stimulus envelopes. Since the calyx of Held synapse is accessible to in vitro and to in vivo recordings, it serves as one of the most elaborate models for studying synaptic transmission in the mammalian brain. Although in such studies, the major emphasis is on synaptic physiology, the interpretation of the data will benefit from an understanding of the MNTB's contribution to auditory signal processing, including possible functional differences in different species. This implies the consideration of possible functional differences in different species. Here, we compare single unit recordings from MNTB principal cells in vivo in three different rodent species: gerbil, mouse and rat. Because of their good low-frequency hearing gerbils are often used in in vivo preparations, while mice and rats are predominantly used in slice preparations. We show that MNTB units in all three species exhibit high firing rates and precise onset-timing. Still there are species-specific specializations that might suggest the preferential use of one species over the others, depending on the scope of the respective investigation.

In the ventral cochlear nucleus Kv1.1 and subunits of HCN1 are colocalized at surfaces of neurons that have low-voltage-activated and hyperpolarization-activated conductances

Principal cells of the ventral cochlear nucleus (VCN) differ in the magnitudes of low-voltage-activated potassium (gKL) and hyperpolarization-activated (gh) conductances that determine the time course of signaling. Octopus cells in mice have large gKL (500 nS) and gh (150 nS), bushy cells have smaller gKL (80 nS) and gh (30 nS), and T stellate cells have little gKL and a small gh (20 nS). gKL Arises through potassium channels of which ∼60% contain Kv1.1 (potassium channels in the shaker or KCNA family) subunits; gh arises through channels that include hyperpolarization and cyclic nucleotide gated (HCN) 1 subunits. The surfaces of cell bodies and dendrites of octopus cells in the dorsocaudal pole, and of similar cells along the ventrolateral edge of the PVCN, were brightly labeled by an antibody against HCN1 that was colocalized with labeling for Kv1.1. More anteriorly neurons with little surface labeling were intermingled among cell bodies and dendrites with surface labeling for both proteins, likely corresponding to T stellate and bushy cells. The membrane-associated labeling patterns for Kv1.1 and HCN1 were consistent with what is known about the distribution and the electrophysiological properties of the principal cells of the VCN. The cytoplasm of large cells and axonal paranodes contained immunofluorescent labeling for only Kv1.1.

Auditory nerve inputs to cochlear nucleus neurons studied with cross-correlation

The strength of synapses between auditory nerve (AN) fibers and ventral cochlear nucleus (VCN) neurons is an important factor in determining the nature of neural integration in VCN neurons of different response types. Synaptic strength was analyzed using cross-correlation of spike trains recorded simultaneously from an AN fiber and a VCN neuron in anesthetized cats. VCN neurons were classified as chopper, primarylike, and onset using previously defined criteria, although onset neurons usually were not analyzed because of their low discharge rates. The correlograms showed an excitatory peak (EP), consistent with monosynaptic excitation, in AN–VCN pairs with similar best frequencies (49% 24/49 of pairs with best frequencies within ±5%). Chopper and primarylike neurons showed similar EPs, except that the primarylike neurons had shorter latencies and shorter-duration EPs. Large EPs consistent with end bulb terminals on spherical bushy cells were not observed, probably because of the low probability of recording from one. The small EPs observed in primarylike neurons, presumably spherical bushy cells, could be derived from small terminals that accompany end bulbs on these cells. EPs on chopper or primarylike-with-notch neurons were consistent with the smaller synaptic terminals on multipolar and globular bushy cells. Unexpectedly, EPs were observed only at sound levels within about 20 dB of threshold, showing that VCN responses to steady tones shift from a 1:1 relationship between AN and VCN spikes at low sound levels to a more autonomous mode of firing at high levels. In the high level mode, the pattern of output spikes seems to be determined by the properties of the postsynaptic spike generator rather than the input spike patterns. The EP amplitudes did not change significantly when the presynaptic spike was preceded by either a short or long interspike interval, suggesting that synaptic depression and facilitation have little effect under the conditions studied here.

Characterization of cochlear nucleus principal cells of Meriones unguiculatus and Monodelphis domestica by use of calcium-binding protein immunolabeling

Antibodies directed against calcium-binding proteins (CaBPs) parvalbumin, calbindin-D28k and calretinin were used as neuronal markers to identify and characterize different principal cell types in the mammalian cochlear nucleus. For this purpose, double immunofluorescence labeling and the combination of CaBP-labeling with pan-neuronal markers were applied to analyze the CaBPs distribution in neurons of the cochlear nucleus (CN) of the Mongolian gerbil ( Meriones unguiculatus) and the gray short-tailed opossum ( Monodelphis domestica). Despite of the fact, that these two mammalian species are not closely related, principal cell types in the CN of the two species showed many corresponding morphological features and similarities in immunolabeling of the CaBPs. Parvalbumin seems not to be suited as a differential neuronal marker in the CN since it is expressed by almost all neurons. In contrast, calbindin and calretinin were more restricted to specific cell types and showed a mostly complementary labeling pattern. As one of the most interesting findings, calbindin and calretinin were predominantly found in subpopulations of globular bushy cells and octopus cells in the ventral CN. Such a neuron-specific CaBP-expression in subpopulations of morphologically defined cell types argues for a more refined classification of CN cell types in Meriones and Monodelphis. Additionally, other cell types (cartwheel cells, unipolar brush cells, fusiform cells) were marked with calbindin or calretinin as well. Calretinin staining was predominantly observed in auditory nerve fibers and their endings including endbulbs of Held in Meriones. Spherical bushy cells showed a different calretinin-immunolabeling in Meriones and Monodelphis. This species-specific difference may be related to adaptive differences in auditory function.

Math5 expression and function in the central auditory system

The basic helix–loop–helix (bHLH) transcription factor Math5 ( Atoh7) is required for retinal ganglion cell (RGC) and optic nerve development. Using Math5-lacZ knockout mice, we have identified an additional expression domain for Math5 outside the eye, in functionally connected structures of the central auditory system. In the adult hindbrain, the cytoplasmic Math5-lacZ reporter is expressed within the ventral cochlear nucleus (VCN), in a subpopulation of neurons that project to medial nucleus of the trapezoid body (MNTB), lateral superior olive (LSO), and lateral lemniscus (LL). These cells were identified as globular and small spherical bushy cells based on their morphology, abundance, distribution within the cochlear nucleus (CN), co-expression of Kv1.1, Kv3.1b and Kcnq4 potassium channels, and projection patterns within the auditory brainstem. Math5- lacZ is also expressed by cochlear root neurons in the auditory nerve. During embryonic development, Math5-lacZ was detected in precursor cells emerging from the caudal rhombic lip from embryonic day (E)12 onwards, consistent with the time course of CN neurogenesis. These cells co-express MafB and are post-mitotic. Math5 expression in the CN was verified by mRNA in situ hybridization, and the identity of positive neurons was confirmed morphologically using a Math5-Cre BAC transgene with an alkaline phosphatase reporter. The hindbrains of Math5 mutants appear grossly normal, with the exception of the CN. Although overall CN dimensions are unchanged, the lacZ-positive cells are significantly smaller in Math5 −/− mice compared to Math5 +/− mice, suggesting these neurons may function abnormally. The auditory brainstem response (ABR) of Math5 mutants was evaluated in a BALB/cJ congenic background. ABR thresholds of Math5 −/− mice were similar to those of wild-type and heterozygous mice, but the interpeak latencies for Peaks II–IV were significantly altered. These temporal changes are consistent with a higher-level auditory processing disorder involving the CN, potentially affecting the integration of binaural sensory information.

Development of Chloride-Mediated Inhibition in Neurons of the Anteroventral Cochlear Nucleus of Gerbil (Meriones unguiculatus)

At the initial stages in neuronal development, GABAergic and glycinergic neurotransmission exert depolarizing responses, assumed to be of importance for maturation, which in turn shift to hyperpolarizing in early postnatal life due to development of the chloride homeostasis system. Spherical bushy cells (SBC) of the mammalian cochlear nucleus integrate excitatory glutamatergic inputs with inhibitory (GABAergic and glycinergic) inputs to compute signals that contribute to sound localization based on interaural time differences. To provide a fundamental understanding of the properties of GABAergic neurotransmission in mammalian cochlear nucleus, we investigated the reversal potential of the GABA-evoked currents (E GABA) by means of gramicidin-perforated-patch recordings in developing SBC. The action of GABA switches from depolarizing to hyperpolarizing by the postnatal day 7 due to the negative shift in E GABA. Furthermore, we studied the expression pattern of the K+-Cl(-)-extruding cotransporter KCC2, previously shown to induce a switch from neonatal Cl(-) efflux to the mature Cl(-) influx in various neuron types, thereby causing a shift from depolarizing to hyperpolarizing GABA action. The KCC2 protein is expressed in SBC already at birth, yet its activity is attained toward the end of the first postnatal week as indicated by pharmacological inhibition. Interruption of the Cl(-) extrusion by [(dihydroindenyl)oxy] alkanoic acid or furosemide gradually shifted E(GABA) in positive direction with increasing maturity, suggesting that KCC2 could be involved in maintaining low [Cl(-)]i after the postnatal day 7 thereby providing the hyperpolarizing Cl(-)-mediated inhibition in SBC.

The role of spontaneous activity in development of the endbulb of Held synapse

In the mouse brainstem cochlear nucleus, the auditory nerve to bushy cell synapse (endbulb of Held) is specialised for rapid, high-fidelity transmission. Development of this synapse is modulated by auditory nerve activity. Here we investigate the role of spontaneous auditory nerve activity in synaptic transmission using deafness ( dn/ dn) mutant mice that have abnormal hair cells and lack spontaneous auditory nerve activity. Evoked and miniature alpha amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor-mediated excitatory post-synaptic currents (eEPSCs, mEPSCs) were compared in deafness and normal mice before the age of hearing onset (postnatal day 7–11: P7–11) using variance-mean, miniature event and tetanic depression analyses. Amplitudes were significantly greater in deafness mice for eEPSCs (2.1-fold), mEPSCs (1.4-fold) and quantal amplitudes (1.5-fold). eEPSCs in deafness mice decayed more rapidly with increasing age, indicating an input-independent transition in post-synaptic AMPA receptor properties. A comparison of normal mice before and after the onset of hearing showed a change in synaptic parameters with an increase in eEPSC (1.7-fold), mEPSC (1.6-fold) and quantal amplitude (1.7-fold) after hearing onset while release probability remained constant (0.5). Overall, the results in deafness mice suggest that synaptic strength is altered in the absence of spontaneous auditory nerve activity.

Bipolar cells in the “grouped retina” of the elephantnose fish (Gnathonemus petersii)

To elucidate the specific properties of retinae with grouped photoreceptors the neural pathways in the outer and inner plexiform layer were studied. Photoreceptor bundles in this species consist of more than 100 rods and up to 50 cones, and are usually regarded as functional units. Golgi impregnation in thick and thin sections and light microscopy were used to identify bipolar cell types linking photoreceptors to amacrine and/or ganglion cells. Nine different types were distinguished based on their dendritic morphology and the position of the axon terminal in the inner plexiform layer. Small cells have dendritic fields smaller than the diameter of a photoreceptor bundle and are contacted mostly by cones. The dendritic field size of bushy cells matches that of a photoreceptor bundle; they are contacted mainly by rods. Flat cells receive about equal input from rods and cones; their dendritic field size exceeds the bundle diameter. Within the three major classes there are subtypes addressing three sublaminae of the inner plexiform layer, the proximal On-centre region (sl b), the distal Off-centre region (sl a) and a central sublayer (sl c) probably with transient activity. These observations suggest that cone vision has a spatial acuity better than the "bundle grain". In rod dominated vision the resolution matches that of the bundles; for this pathway, the hypothesis of the bundle as a functional unit is confirmed. The mesopic flat cell pathway has a resolution inferior to the "bundle grain"; it may therefore be dedicated to movement detection.

Voltage-Sensitive Conductances of Bushy Cells of the Mammalian Ventral Cochlear Nucleus

Bushy cells in the ventral cochlear nucleus convey firing of auditory nerve fibers to neurons in the superior olivary complex that compare the timing and intensity of sounds at the two ears and enable animals to localize sound sources in the horizontal plane. Three voltage-sensitive conductances allow bushy cells to convey acoustic information with submillisecond temporal precision. All bushy cells have a low-voltage-activated, alpha-dendrotoxin (alpha-DTX)-sensitive K(+) conductance (g(KL)) that was activated by depolarization past -70 mV, was half-activated at -39.0 +/- 1.7 (SE) mV, and inactivated approximately 60% over 5 s. Maximal g(KL) varied between 40 and 150 nS (mean: 80.8 +/- 16.7 nS). An alpha-DTX-insensitive, tetraethylammonium (TEA)-sensitive, K(+) conductance (g(KH)) was activated at voltages positive to -40 mV, was half-activated at -18.1 +/- 3.8 mV, and inactivated by 90% over 5 s. Maximal g(KH) varied between 35 and 80 nS (mean: 58.2 +/- 6.5 nS). A ZD7288-sensitive, mixed cation conductance (g(h)) was activated by hyperpolarization greater than -60 mV and half-activated at -83.1 +/- 1.1 mV. Maximum g(h) ranged between 14.5 and 56.6 nS (mean: 30.0 +/- 5.5 nS). 8-Br-cAMP shifted the voltage sensitivity of g(h) positively. Changes in temperature stably altered the steady-state magnitude of I(h). Both g(KL) and g(KH) contribute to repolarizing action potentials and to sharpening synaptic potentials. Those cells with the largest g(h) and the largest g(KL) fired least at the onset of a depolarization, required the fastest depolarizations to fire, and tended to be located nearest the nerve root.

A Developmental Switch to GABAergic Inhibition Dependent on Increases in Kv1-Type K+Currents

Mature nucleus magnocellularis (NM) neurons, the avian homolog of bushy cells of the mammalian anteroventral cochlear nucleus, maintain high [Cl-]i and depolarize in response to GABA. Depolarizing GABAergic postsynaptic potentials (GPSPs) activate both the synaptic conductance and large outward currents, which, when coupled together, inhibit spikes via shunting and spike threshold accommodation. We studied the maturation of the synaptic and voltage-dependent components of inhibition in embryonic NM neurons using whole-cell and gramicidin-perforated patch-clamp techniques to measure Cl- reversal potential, GABAergic synaptic responses, and voltage-dependent outward currents. We found that GABA enhanced excitability in immature NM neurons, undergoing a switch to inhibitory between embryonic day 14 (E14) and E18. Low-voltage-activated Kv1-type (dendrotoxin-I sensitive) K+ currents increased in amplitude between E14 and E18, whereas Cl- reversal potential and synaptic conductances remained relatively stable during this period. GABA was rendered inhibitory because of this increase in low-voltage activated outward currents. GPSPs summed with other inputs to increase spike probability at E14. GPSPs shunted spikes at E18, but blocking Kv1 channels transformed this inhibition to excitation, similar to E14 neurons. Subthreshold depolarizing current steps, designed to activate outward currents similar to depolarizing GPSPs, enhanced excitability at E14 but inhibited spiking in E18 neurons. Blocking Kv1 channels reversed this effect, rendering current steps excitatory. We present the novel finding that the developmental transition of GABAergic processing from increasing neuronal excitability to inhibiting spiking can depend on changes in the expression of voltage-gated channels rather than on a change in Cl- reversal potential.

The commissural pathway and cochlear nucleus bushy neurons: An in vivo intracellular investigation

A direct commissural connection formed between cochlear nuclei allows information from the contralateral ear to rapidly influence the processing of the ascending auditory signal. Among the neuronal groups proposed to both receive, and contribute to, commissural input is the bushy cell population in the ventral cochlear nucleus (VCN). In this in vivo electrophysiological study we examine the intracellular recordings of bushy neurons during electrical stimulation of the contralateral cochlear nucleus (CN) for evidence of both their contribution to, and input from commissural projections. Activation of the commissural pathway revealed short-latency fast hyperpolarisation in 19.5% of the 41 bushy neurons examined. The hyperpolarising potentials were small in amplitude, displayed a highly variable time course between neurons, and in some cases were eliminated with injection of depolarising current. There was no indication of antidromic activity, or short-latency excitatory potentials. These results suggest that i) bushy neurons do not contribute projections to the commissural connection, and ii) a small portion of bushy neurons are hyperpolarised following commissural stimulation.

Frequency Selectivity Behaviour in the Auditory Midbrain:Implications of Model Study

By numerical simulations on frequency dependence of the spikingthreshold, i.e. on the critical amplitude of periodic stimulus, for aneuron to fire, we find that bushy cells in the cochlear nuclear exhibitfrequency selectivity behaviour. However, the selective frequency bandof a bushy cell is far away from that of the preferred spectral range inhuman and mammal auditory perception. The mechanism underlying thisneural activity is also discussed. Further studies show that the ionchannel densities have little impact on the selective frequency band ofbushy cells. These findings suggest that the neuronal behaviour offrequency selectivity in bushy cells at both the single cell andpopulation levels may be not functionally relevant to frequencydiscrimination. Our results may reveal a neural hint to thereconsideration on the bushy cell functional role in auditoryinformation processing of sound frequency.

Development of Spontaneous Miniature EPSCs in Mouse AVCN Neurons During a Critical Period of Afferent-Dependent Neuron Survival

During a critical period prior to hearing onset, cochlea ablation leads to massive neuronal death in the mouse anteroventral cochlear nucleus (AVCN), where cell survival is believed to depend on glutamatergic input. We investigated the development of spontaneous miniature excitatory postsynaptic currents (mEPSCs) in AVCN neurons using whole cell patch-clamp techniques during [postnatal day 7 (P7)] and after (P14, P21) this critical period. We also examined the effects of unilateral cochlea ablation on mEPSC development. The two main AVCN neuron types, bushy and stellate cells, were distinguished electrophysiologically. Bushy cell mEPSCs became more frequent and faster between P7 and P14/P21 but with little change in amplitude. Dendritic filtering of mEPSCs was not detected as indicated by the lack of correlation between 10 and 90% rise times and decay time constants. Seven days after cochlea ablation at P7 or P14, mEPSCs in surviving bushy cells were similar to controls, except that rise and decay times were positively correlated (R = 0.31 and 0.14 for surgery at P7 and P14, respectively). Consistent with this evidence for a shift of synaptic activity from the somata to the dendrites, SV2 staining (a synaptic vesicle marker) forms a ring around somata of control but not experimental bushy cells. In contrast, mEPSCs of stellate cells showed few significant changes over these ages with or without cochlea ablation. Taken together, mEPSCs in mouse AVCN bushy cells show dramatic developmental changes across this critical period, and cochlea ablation may lead to the emergence of excitatory synaptic inputs impinging on bushy cell dendrites.

Temporal Coding by Cochlear Nucleus Bushy Cells in DBA/2J Mice with Early Onset Hearing Loss

The bushy cells of the anterior ventral cochlear nucleus (AVCN) preserve or improve the temporal coding of sound information arriving from auditory nerve fibers (ANF). The critical cellular mechanisms entailed in this process include the specialized nerve terminals, the endbulbs of Held, and the membrane conductance configuration of the bushy cell. In one strain of mice (DBA/2J), an early-onset hearing loss can cause a reduction in neurotransmitter release probability, and a smaller and slower spontaneous miniature excitatory postsynaptic current (EPSC) at the endbulb synapse. In the present study, by using a brain slice preparation, we tested the hypothesis that these changes in synaptic transmission would degrade the transmission of timing information from the ANF to the AVCN bushy neuron. We show that the electrical excitability of bushy cells in hearing-impaired old DBA mice was different from that in young, normal-hearing DBA mice. We found an increase in the action potential (AP) firing threshold with current injection; a larger AP afterhyperpolarization; and an increase in the number of spikes produced by large depolarizing currents. We also tested the temporal precision of bushy cell responses to high-frequency stimulation of the ANF. The standard deviation of spikes (spike jitter) produced by ANF-evoked excitatory postsynaptic potentials (EPSPs) was largely unaffected in old DBA mice. However, spike entrainment during a 100-Hz volley of EPSPs was significantly reduced. This was not a limitation of the ability of bushy cells to fire APs at this stimulus frequency, because entrainment to trains of current pulses was unaffected. Moreover, the decrease in entrainment is not attributable to increased synaptic depression. Surprisingly, the spike latency was 0.46 ms shorter in old DBA mice, and was apparently attributable to a faster conduction velocity, since the evoked excitatory postsynaptic current (EPSC) latency was shorter in old DBA mice as well. We also tested the contribution of the low-voltage-activated K+ conductance (g (KLV)) on the spike latency by using dynamic clamp. Alteration in g (KLV) had little effect on the spike latency. To test whether these changes in DBA mice were simply a result of continued postnatal maturation, we repeated the experiments in CBA mice, a strain that shows normal hearing thresholds through this age range. CBA mice exhibited no reduction in entrainment or increased spike jitter with age. We conclude that the ability of AVCN bushy neurons to reliably follow ANF EPSPs is compromised in a frequency-dependent fashion in hearing-impaired mice. This effect can be best explained by an increase in spike threshold.

Rate thresholds determine the precision of temporal integration in principal cells of the ventral cochlear nucleus

The three types of principal cells of the ventral cochlear nucleus (VCN), bushy, octopus, and T stellate, differ in the detection of coincidence among synaptic inputs. To explore the role of the action-potential-generation mechanism in the detection of coincident inputs, we examined responses to depolarizing currents that increased at varying rates. To fire an action potential, bushy cells, likely of the globular subtype, had to be depolarized faster than 4.8 ± 2.8 mV/ms, octopus cells faster than 9.5 ± 3.6 mV/ms, and T stellate cells fired irrespective of the rate of depolarization. The threshold rate of depolarization permitted definition of a time window over which depolarization could contribute to generating action potentials. This integration window differed between cell types. It was 5.3 ± 1.8 ms for bushy cells and 1.4 ± 0.3 ms for octopus cells. T Stellate cells fired action potentials in response to even slow depolarizations, showing that their integration window was unlimited so that temporal summation in these cells is limited by the time course of synaptic potentials. The rate of depolarization threshold in octopus and bushy cells was decreased by α-dendrotoxin while T stellate cells were largely insensitive to α-dendrotoxin indicating that low-voltage-activated K + conductances ( g KL) are important determinants of the integration window.

Differential expression of cytoskeletal genes in the cochlear nucleus

The relationship between structure and function is clearly illustrated by emerging evidence demonstrating the role of the neuronal cytoskeleton in physiological processes. For example, alterations in axonal caliber, a feature of the cytoskeleton, have been shown to affect reflex arc latencies and are prominent features of several neuropathological disorders. Even in the nonpathologic situation, however, axonal diameter may be a crucial element for the normal function of specialized auditory neurons. To investigate this relationship, we used serial analysis of gene expression and microarray analyses to characterize the expression of cytoskeletal genes in the central auditory system. These data, confirmed by real-time RT-PCR, identified differential expression of intermediate neurofilament transcripts (i.e., Nefh, Nef3, and Nfl) among the subdivisions of the cochlear nucleus. In situ hybridization was used to identify specific classes of neurons within the cochlear nucleus expressing these neurofilament genes. Robust neurofilament expression was seen in bushy cells and cochlear nerve root neurons, suggesting an association between cytoskeletal structure and rapid conduction velocities. Gene expression data were also identified for other classes of cytoskeletal and structural genes important in neuronal function. These results may help to explain some causes of hearing loss in hereditary neuropathies and provide an anatomic basis for understanding normal neuronal function in the central auditory system.

Postnatal development of a large auditory nerve terminal: The endbulb of Held in cats

The endbulbs of Held are formed by the ascending branches of myelinated auditory nerve fibers and represent one of the largest synaptic endings in the brain. Most of the developmental changes in structure occur during the first 30 postnatal days of age. The neonatal endbulb begins as a flattened expansion with many filopodia, resembling a growth cone and characterized by numerous puncta adherentia and synapses associated with small postsynaptic densities; the most impressive feature of the ending at this age is its highly irregular plasma membrane that interdigitates with that of the postsynaptic spherical bushy cell. During these first 30 days, the number of puncta adherentia diminishes, postsynaptic densities nearly double in size, intermembraneous cisternae emerge, and plasma membranes flatten. These features endow the endbulb with an adult-like appearance. On the other hand, synaptic vesicle density increases progressively from approximately 50/μm 2 at birth to 100/μm 2 at adulthood. Mitochondria size remains constant over this developmental period but mitochondrial volume fraction increases until 60 days postnatal. Although many features of endbulb morphology stabilize by 30 days, other features suggest that endbulb development continues into the third month of age. Many of these observations correlate with the maturation of physiological response properties and suggest issues for further study.

Temporal Coding by Cochlear Nucleus Bushy Cells in DBA/2J Mice with Early Onset Hearing Loss

Temporal Coding by Cochlear Nucleus Bushy Cells in DBA/2J Mice with Early Onset Hearing Loss