scholarly journals Context-Dependent Effects of NMDA Receptors on Precise Timing Information at the Endbulb of Held in the Cochlear Nucleus

2009 ◽  
Vol 102 (5) ◽  
pp. 2627-2637 ◽  
Author(s):  
Lioudmila Pliss ◽  
Hua Yang ◽  
Matthew A. Xu-Friedman
Keyword(s):  
Cochlear Nucleus ◽  
Spike Timing ◽  
Temporal Information ◽  
Synaptic Activity ◽  
Dynamic Clamp ◽  
Fast Kinetics ◽  
Precise Timing ◽  
Endbulb Of Held ◽  
Slow Kinetics ◽  
Bushy Cells

Many synapses contain both AMPA receptors (AMPAR) and N-methyl-d-aspartate receptors (NMDAR), but their different roles in synaptic computation are not clear. We address this issue at the auditory nerve fiber synapse (called the endbulb of Held), which is formed on bushy cells of the cochlear nucleus. The endbulb refines and relays precise temporal information to nuclei responsible for sound localization. The endbulb has a number of specializations that aid precise timing, including AMPAR-mediated excitatory postsynaptic currents (EPSCs) with fast kinetics. Voltage-clamp experiments in mouse brain slices revealed that slow NMDAR EPSCs are maintained at mature endbulbs, contributing a peak conductance of around 10% of the AMPAR-mediated EPSC. During repetitive synaptic activity, AMPAR EPSCs depressed and NMDAR EPSCs summated, thereby increasing the relative importance of NMDARs. This could impact temporal precision of bushy cells because of the slow kinetics of NMDARs. We tested this by blocking NMDARs and quantifying bushy cell spike timing in current clamp when single endbulbs were activated. These experiments showed that NMDARs contribute to an increased probability of firing, shorter latency, and reduced jitter. Dynamic-clamp experiments confirmed this effect and showed it was dose-dependent. Bushy cells can receive inputs from multiple endbulbs. When we applied multiple synaptic inputs in dynamic clamp, NMDARs had less impact on spike timing. NMDAR conductances much higher than mature levels could disrupt spiking, which may explain its downregulation during development. Thus mature NMDAR expression can support the conveying of precise temporal information at the endbulb, depending on the stimulus conditions.

scholarly journals Impact of Synaptic Depression on Spike Timing at the Endbulb of Held

2009 ◽  
Vol 102 (3) ◽  
pp. 1699-1710 ◽  
Author(s):  
Hua Yang ◽  
Matthew A. Xu-Friedman
Keyword(s):  
Brain Slices ◽  
Temporal Distribution ◽  
Response Probability ◽  
Spike Timing ◽  
Lower Probability ◽  
Dynamic Clamp ◽  
Timing Information ◽  
Highly Active ◽  
Endbulb Of Held ◽  
Activity Dependent

Many synapses show short-term depression, but it is not well understood what functional purpose depression serves and whether its effects are beneficial or detrimental to information processing. We study this issue at the synapse made by auditory-nerve (AN) fibers onto bushy cells (BCs) of the cochlear nucleus, called the “endbulb of Held.” AN fibers carry timing information about sounds and converge on BCs, which relay timing information to brain areas responsible for sound localization. Dynamic-clamp recordings of BCs in mouse brain slices indicated that nonphase-locked inputs influenced the contribution of phase-locked inputs when all inputs had equal strength. We evaluated whether this situation depended on activity-dependent synaptic plasticity. Voltage-clamp recordings indicated that the amount of depression varied over the population of endbulbs, but sibling endbulbs terminating on the same BC had similar plasticity. We tested the effects of endbulb depression on BC spiking using dynamic clamp. Under most conditions, increasing depression led to lower probability of BC spiking. However, the effects on spike timing were highly context dependent. When all inputs carried uniform timing information, depression indirectly affected BC spike precision, by determining how many inputs were required to cross threshold. Earlier work has indicated that this interacts with the temporal distribution of inputs to determine BC spike precision. When inputs carried different timing information, depression greatly improved BC precision by suppressing highly active inputs carrying little phase-locked information. These data suggest that endbulbs with different depression characteristics could produce BCs that enhance response probability or timing under different stimulus conditions.

Differential contributions of voltage-gated potassium channel subunits in enhancing temporal coding in the bushy cells of the ventral cochlear nucleus

2021 ◽  
Author(s):  
Mingyu Fu ◽  
Lu Zhang ◽  
Xiao Xie ◽  
Ningqian Wang ◽  
Zhongju Xiao
Keyword(s):  
Cochlear Nucleus ◽  
Spike Timing ◽  
Temporal Coding ◽  
Membrane Properties ◽  
Membrane Excitability ◽  
Patch Clamp Recording ◽  
Voltage Gated ◽  
Ventral Cochlear Nucleus ◽  
Kv Channels ◽  
Bushy Cells

Temporal coding precision of bushy cells in the ventral cochlear nucleus (VCN), critical for sound localization and communication, depends on the generation of rapid and temporally precise action potentials (APs). Voltage-gated potassium (Kv) channels are critically involved in this. The bushy cells in rat VCN express Kv1.1, 1.2, 1.3, 1.6, 3.1, 4.2 and 4.3 subunits. The Kv1.1 subunit contributes to the generation of a temporally precise single AP. However, the understanding of the functions of other Kv subunits expressed in the bushy cells is limited. Here, we investigated the functional diversity of Kv subunits concerning their contributions to temporal coding. We characterized the electrophysiological properties of the Kv channels with different subunits using whole-cell patch-clamp recording and pharmacological methods. The neuronal firing pattern changed from single to multiple APs only when the Kv1.1 subunit was blocked. The Kv subunits, including the Kv1.1, 1.2, 1.6 or 3.1, were involved in enhancing temporal coding by lowering membrane excitability, shortening AP latencies, reducing jitter and regulating AP kinetics. Meanwhile, all the Kv subunits contributed to rapid repolarization and sharpening peaks by narrowing half-width and accelerating fall rate, while the Kv1.1 subunit also affected the depolarization of AP. The Kv1.1, 1.2 and 1.6 subunits endowed bushy cells with a rapid time constant and a low input resistance of membrane for enhancing spike timing precision. The present results indicate that the Kv channels differentially affect intrinsic membrane properties to optimize the generation of rapid and reliable APs for temporal coding.

Fast Inhibition Alters First Spike Timing in Auditory Brainstem Neurons

2004 ◽  
Vol 92 (4) ◽  
pp. 2615-2621 ◽  
Author(s):  
Antonio G. Paolini ◽  
Janine C. Clarey ◽  
Karina Needham ◽  
Graeme M. Clark
Keyword(s):  
Lateral Inhibition ◽  
Cochlear Nucleus ◽  
Stellate Cell ◽  
Discharge Rate ◽  
Stellate Cells ◽  
Auditory Pathway ◽  
Auditory Brainstem ◽  
Spike Timing ◽  
Inhibitory Neurons

Within the first processing site of the central auditory pathway, inhibitory neurons (D stellate cells) broadly tuned to tonal frequency project on narrowly tuned, excitatory output neurons (T stellate cells). The latter is thought to provide a topographic representation of sound spectrum, whereas the former is thought to provide lateral inhibition that improves spectral contrast, particularly in noise. In response to pure tones, the overall discharge rate in T stellate cells is unlikely to be suppressed dramatically by D stellate cells because they respond primarily to stimulus onset and provide fast, short-duration inhibition. In vivo intracellular recordings from the ventral cochlear nucleus (VCN) showed that, when tones were presented above or below the characteristic frequency (CF) of a T stellate neuron, they were inhibited during depolarization. This resulted in a delay in the initial action potential produced by T stellate cells. This ability of fast inhibition to alter the first spike timing of a T stellate neuron was confirmed by electrically activating the D stellate cell pathway that arises in the contralateral cochlear nucleus. Delay was also induced when two tones were presented: one at CF and one outside the frequency response area of the T stellate neuron. These findings suggest that the traditional view of lateral inhibition within the VCN should incorporate delay as one of its principle outcomes.

Mechanisms of Onset Responses in Octopus Cells of the Cochlear Nucleus: Implications of a Model

1997 ◽  
Vol 78 (2) ◽  
pp. 872-883 ◽  
Author(s):  
Yidao Cai ◽  
Edward J. Walsh ◽  
JoAnn McGee
Keyword(s):  
Cochlear Nucleus ◽  
Response Pattern ◽  
Compartment Model ◽  
Ionic Channels ◽  
Nerve Fibers ◽  
Threshold Channel ◽  
Slow Kinetics ◽  
Low Threshold ◽  
Onset Response ◽  
Onset Responses

Cai, Yidao, Edward J. Walsh, and JoAnn McGee. Mechanisms of onset responses in octopus cells of the cochlear nucleus: implications of a model. J. Neurophysiol. 78: 872–883, 1997. The octopus cells of the posteroventral cochlear nucleus receive inputs from auditory-nerve fibers and form one of the major ascending auditory pathways. They respond to acoustic and electrical stimulation transiently and are believed to carry temporal information in the precise timing of their action potentials. The mechanism whereby onset responses are generated is not clear. Proposals aimed at elucidating the mechanism range from neural circuitry and/or inhibition, “depolarization block” (or inactivation of Na+ channels), and the involvement of a 4-aminopyridine (4-AP)–sensitive, low-threshold channel (KLT). In the present study, we used a compartment model to investigate possible mechanisms. The model cell contains a soma, an axon, and four passive dendrites. Four kinds of ionic channels were included in the soma compartment: the Hodgkin-Huxley–like Na+ and K+ channels, a 4-AP–sensitive, low-threshold channel, KLT, and a Cs+-sensitive, hyperpolarization-activated inward rectifier, I h . DC currents and half-wave–rectified sinewaves were used as stimuli. Our results showed that an onset response can be generated in the absence of neuronal circuitry of any form, thus suggesting that the onset response in octopus cells is regulated intrinsically. Among the many factors involved, low-input impedance, partly contributed by I h , appears to be essential to the basic onset response pattern; also, the KLT conductance plays a major role, whereas the inactivation of Na+ channels probably plays only a secondary role. The dynamics of I h also can modify the response pattern, but due to its slow kinetics, its role is probably limited to longer-term regulation under the conditions simulated in this study.

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

2007 ◽  
Vol 97 (1) ◽  
pp. 635-646 ◽  
Author(s):  
Yong Lu ◽  
Julie A. Harris ◽  
Edwin W. Rubel
Keyword(s):  
Critical Period ◽  
Stellate Cells ◽  
Synaptic Activity ◽  
Developmental Changes ◽  
Synaptic Inputs ◽  
Whole Cell Patch Clamp ◽  
Bushy Cell ◽  
Anteroventral Cochlear Nucleus ◽  
Decay Times ◽  
Bushy Cells

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.

scholarly journals Synaptic Transmission at the Cochlear Nucleus Endbulb Synapse During Age-Related Hearing Loss in Mice

2005 ◽  
Vol 94 (3) ◽  
pp. 1814-1824 ◽  
Author(s):  
Yong Wang ◽  
Paul B. Manis
Keyword(s):  
Hearing Loss ◽  
Synaptic Transmission ◽  
Cochlear Nucleus ◽  
Auditory Nerve ◽  
High Frequency ◽  
Nerve Activity ◽  
Synaptic Release ◽  
Endbulb Of Held ◽  
Age Related ◽  
Age Related Hearing Loss

Age-related hearing loss (AHL) typically starts from high-frequency regions of the cochlea and over time invades lower-frequency regions. During this progressive hearing loss, sound-evoked activity in spiral ganglion cells is reduced. DBA mice have an early onset of AHL. In this study, we examined synaptic transmission at the endbulb of Held synapse between auditory nerve fibers and bushy cells in the anterior ventral cochlear nucleus (AVCN). Synaptic transmission in hearing-impaired high-frequency areas of the AVCN was altered in old DBA mice. The spontaneous miniature excitatory postsynaptic current (mEPSC) frequency was substantially reduced (about 60%), and mEPSCs were significantly slower (about 115%) and smaller (about 70%) in high-frequency regions of old (average age 45 days) DBA mice compared with tonotopically matched regions of young (average age 22 days) DBA mice. Moreover, synaptic release probability was about 30% higher in high-frequency regions of young DBA than that in old DBA mice. Auditory nerve–evoked EPSCs showed less rectification in old DBA mice, suggesting recruitment of GluR2 subunits into the AMPA receptor complex. No similar age-related changes in synaptic release or EPSCs were found in age-matched, normal hearing young and old CBA mice. Taken together, our results suggest that auditory nerve activity plays a critical role in maintaining normal synaptic function at the endbulb of Held synapse after the onset of hearing. Auditory nerve activity regulates both presynaptic (release probability) and postsynaptic (receptor composition and kinetics) function at the endbulb synapse after the onset of hearing.

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