scholarly journals Sparsely Distributed, Pre-synaptic Kv3 K+ Channels Control Spontaneous Firing and Cross-Unit Synchrony via the Regulation of Synaptic Noise in an Auditory Brainstem Circuit

2021 ◽  
Vol 15 ◽  
Author(s):  
Timothy OIsen ◽  
Alberto Capurro ◽  
Maša Švent ◽  
Nadia Pilati ◽  
Charles Large ◽  
...  
Keyword(s):  
Spontaneous Activity ◽  
Calcium Influx ◽  
Auditory Brainstem ◽  
Spike Timing ◽  
Dorsal Cochlear Nucleus ◽  
Current Modulation ◽  
Transgenic Mouse Line ◽  
Synaptic Modulation ◽  
Acoustic Information ◽  
Synaptic Noise

Spontaneous subthreshold activity in the central nervous system is fundamental to information processing and transmission, as it amplifies and optimizes sub-threshold signals, thereby improving action potential initiation and maintaining reliable firing. This form of spontaneous activity, which is frequently considered noise, is particularly important at auditory synapses where acoustic information is encoded by rapid and temporally precise firing rates. In contrast, when present in excess, this form of noise becomes detrimental to acoustic information as it contributes to the generation and maintenance of auditory disorders such as tinnitus. The most prominent contribution to subthreshold noise is spontaneous synaptic transmission (synaptic noise). Although numerous studies have examined the role of synaptic noise on single cell excitability, little is known about its pre-synaptic modulation owing in part to the difficulties of combining noise modulation with monitoring synaptic release. Here we study synaptic noise in the auditory brainstem dorsal cochlear nucleus (DCN) of mice and show that pharmacological potentiation of Kv3 K+ currents reduces the level of synaptic bombardment onto DCN principal fusiform cells. Using a transgenic mouse line (SyG37) expressing SyGCaMP2-mCherry, a calcium sensor that targets pre-synaptic terminals, we show that positive Kv3 K+ current modulation decreases calcium influx in a fifth of pre-synaptic boutons. Furthermore, while maintaining rapid and precise spike timing, positive Kv3 K+ current modulation increases the synchronization of local circuit neurons by reducing spontaneous activity. In conclusion, our study identifies a unique pre-synaptic mechanism which reduces synaptic noise at auditory synapses and contributes to the coherent activation of neurons in a local auditory brainstem circuit. This form of modulation highlights a new therapeutic target, namely the pre-synaptic bouton, for ameliorating the effects of hearing disorders which are dependent on aberrant spontaneous activity within the central auditory system.

scholarly journals Dynamic modulation of spike timing-dependent calcium influx during corticostriatal upstates

2013 ◽  
Vol 110 (7) ◽  
pp. 1631-1645 ◽  
Author(s):  
R. C. Evans ◽  
Y. M. Maniar ◽  
K. T. Blackwell
Keyword(s):  
Synaptic Plasticity ◽  
Slow Wave Sleep ◽  
Calcium Influx ◽  
Spike Timing ◽  
Medium Spiny Neuron ◽  
Calcium Transients ◽  
Biophysical Model ◽  
Published Data ◽  
High Calcium

The striatum of the basal ganglia demonstrates distinctive upstate and downstate membrane potential oscillations during slow-wave sleep and under anesthetic. The upstates generate calcium transients in the dendrites, and the amplitude of these calcium transients depends strongly on the timing of the action potential (AP) within the upstate. Calcium is essential for synaptic plasticity in the striatum, and these large calcium transients during the upstates may control which synapses undergo plastic changes. To investigate the mechanisms that underlie the relationship between calcium and AP timing, we have developed a realistic biophysical model of a medium spiny neuron (MSN). We have implemented sophisticated calcium dynamics including calcium diffusion, buffering, and pump extrusion, which accurately replicate published data. Using this model, we found that either the slow inactivation of dendritic sodium channels (NaSI) or the calcium inactivation of voltage-gated calcium channels (CDI) can cause high calcium corresponding to early APs and lower calcium corresponding to later APs. We found that only CDI can account for the experimental observation that sensitivity to AP timing is dependent on NMDA receptors. Additional simulations demonstrated a mechanism by which MSNs can dynamically modulate their sensitivity to AP timing and show that sensitivity to specifically timed pre- and postsynaptic pairings (as in spike timing-dependent plasticity protocols) is altered by the timing of the pairing within the upstate. These findings have implications for synaptic plasticity in vivo during sleep when the upstate-downstate pattern is prominent in the striatum.

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.

Auditory processing of complex sounds: an overview

1992 ◽  
Vol 336 (1278) ◽  
pp. 295-306 ◽  
Keyword(s):  
Auditory System ◽  
Auditory Processing ◽  
Dynamic Range ◽  
Auditory Brainstem ◽  
Frequency Selectivity ◽  
Dorsal Cochlear Nucleus ◽  
Cochlear Nerve ◽  
Complex Sounds ◽  
Wide Range ◽  
Time Coding

The past 30 years has seen a remarkable development in our understanding of how the auditory system - particularly the peripheral system - processes complex sounds. Perhaps the most significant has been our understanding of the mechanisms underlying auditory frequency selectivity and their importance for normal and impaired auditory processing. Physiologically vulnerable cochlear filtering can account for many aspects of our normal and impaired psychophysical frequency selectivity with important consequences for the perception of complex sounds. For normal hearing, remarkable mechanisms in the organ of Corti, involving enhancement of mechanical tuning (in mammals probably by feedback of electro-mechanically generated energy from the hair cells), produce exquisite tuning, reflected in the tuning properties of cochlear nerve fibres. Recent comparisons of physiological (cochlear nerve) and psychophysical frequency selectivity in the same species indicate that the ear’s overall frequency selectivity can be accounted for by this cochlear filtering, at least in band width terms. Because this cochlear filtering is physiologically vulnerable, it deteriorates in deleterious conditions of the cochlea - hypoxia, disease, drugs, noise overexposure, mechanical disturbance - and is reflected in impaired psychophysical frequency selectivity. This is a fundamental feature of sensorineural hearing loss of cochlear origin, and is of diagnostic value. This cochlear filtering, particularly as reflected in the temporal patterns of cochlear fibres to complex sounds, is remarkably robust over a wide range of stimulus levels. Furthermore, cochlear filtering properties are a prime determinant of the ‘place’ and ‘time’ coding of frequency at the cochlear nerve level, both of which appear to be involved in pitch perception. The problem of how the place and time coding of complex sounds is effected over the ear’s remarkably wide dynamic range is briefly addressed. In the auditory brainstem, particularly the dorsal cochlear nucleus, are inhibitory mechanisms responsible for enhancing the spectral and temporal contrasts in complex sounds. These mechanisms are now being dissected neuropharmacologically. At the cortical level, mechanisms are evident that are capable of abstracting biologically relevant features of complex sounds. Fundamental studies of how the auditory system encodes and processes complex sounds are vital to promising recent applications in the diagnosis and rehabilitation of the hearing impaired.

Physiological studies on neurons in the dorsal cochlear nucleus of cat

1986 ◽  
Vol 56 (2) ◽  
pp. 287-307 ◽  
Author(s):  
W. S. Rhode ◽  
P. H. Smith
Keyword(s):  
Spontaneous Activity ◽  
Cochlear Nucleus ◽  
Response Pattern ◽  
Phase Locking ◽  
Molecular Layer ◽  
Dorsal Cochlear Nucleus ◽  
Fusiform Cell ◽  
Graded Response ◽  
Temporal Encoding ◽  
Onset Response

Results reported here support the conclusion that an individual neuron in the dorsal cochlear nucleus (DCN) can exhibit pauser, buildup, and chopper patterns in response to tone pips. Fusiform cells have been previously identified as the principal cell exhibiting these patterns. Fusiform cells can also exhibit an onset response followed by suppression of spontaneous activity at their characteristic frequency (CF). Off CF only suppression is seen. These neurons are characterized by a restricted excitatory region near threshold. All these cells can exhibit nonmonotonic rate curves, narrow excitatory regions, and inhibitory sidebands. Nonmonotonicity occurred in 34% of pausers, 52% of buildup, 89% of onsets with a graded response, and 50% overall in the DCN cells. Chopper units occur as often as the other types combined in the DCN. Only 14% show nonmonotonic rate curves. Those with high-spontaneous activity also show inhibitory sidebands. Cells with a predominant buildup pattern occur most frequently in the fusiform cell layer, whereas pausers occur throughout the DCN below the molecular layer. Intracellular potentials often reflect the average response pattern. Sharply delimited response areas indicate that these cells may be useful for performing a spectral analysis. These cells show almost no phase locking suggesting that temporal encoding is an unlikely function. It is suggested that the effects of anesthetic on the function of the DCN is not as marked as previously indicated.

scholarly journals Effect of changes in action potential shape on calcium currents and transmitter release in a calyx–type synapse of the rat auditory brainstem

1999 ◽  
Vol 354 (1381) ◽  
pp. 347-355 ◽  
Author(s):  
J. G. G. Borst ◽  
B. Sakmann
Keyword(s):  
Action Potential ◽  
Transmitter Release ◽  
Time Course ◽  
Calcium Influx ◽  
Auditory Brainstem ◽  
Calcium Currents ◽  
Medial Nucleus ◽  
Potential Shape ◽  
Presynaptic Calcium ◽  
Rat Brainstem

We studied the relation between the size of presynaptic calcium influx and transmitter release by making simultaneous voltage clamp recordings from presynaptic terminals, the calyces of Held and postsynaptic cells, the principal cells of the medial nucleus of the trapezoid body, in slices of the rat brainstem. Calyces were voltage clamped with different action potential waveforms. The amplitude of the excitatory postsynaptic currents depended supralinearly on the size of the calcium influx, in the absence of changes in the time–course of the calcium influx. This result is in agreement with the view thact at this synapse most vesicles are released by the combined action of multiple calcium channels.

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

1998 ◽  
Vol 783 (2) ◽  
pp. 219-226 ◽  
Author(s):  
Kejian Chen ◽  
Hardress J Waller ◽  
Donald A Godfrey
Keyword(s):  
Spontaneous Activity ◽  
Cochlear Nucleus ◽  
Dorsal Cochlear Nucleus

scholarly journals Where’s the noise? Key features of neuronal variability and inference emerge from self-organized learning

2014 ◽  
Author(s):  
Christoph Hartmann ◽  
Andreea Lazar ◽  
Jochen Triesch
Keyword(s):  
Spontaneous Activity ◽  
Network Model ◽  
Neural Circuit ◽  
Intrinsic Noise ◽  
Spike Timing ◽  
Homeostatic Plasticity ◽  
Neural Recordings ◽  
Self Organized ◽  
Key Features ◽  
Neural Variability

AbstractTrial-to-trial variability and spontaneous activity of cortical recordings have been suggested to reflect intrinsic noise. This view is currently challenged by mounting evidence for structure in these phenomena: Trial-to-trial variability decreases following stimulus onset and can be predicted by previous spontaneous activity. This spontaneous activity is similar in magnitude and structure to evoked activity and can predict decisions. Allof the observed neuronal properties described above can be accounted for, at an abstract computational level, by the sampling-hypothesis, according to which response variability reflects stimulus uncertainty. However, a mechanistic explanation at the level of neural circuit dynamics is still missing.In this study, we demonstrate that all of these phenomena can be accounted for by a noise-free self-organizing recurrent neural network model (SORN). It combines spike-timing dependent plasticity (STDP) and homeostatic mechanisms in a deterministic network of excitatory and inhibitory McCulloch-Pitts neurons. The network self-organizes to spatio-temporally varying input sequences.We find that the key properties of neural variability mentioned above develop in this model as the network learns to perform sampling-like inference. Importantly, the model shows high trial-to-trial variability although it is fully deterministic. This suggests that the trial-to-trial variability in neural recordings may not reflect intrinsic noise. Rather, it may reflect a deterministic approximation of sampling-like learning and inference. The simplicity of the model suggests that these correlates of the sampling theory are canonical properties of recurrent networks that learn with a combination of STDP and homeostatic plasticity mechanisms.Author SummaryNeural recordings seem very noisy. If the exact same stimulus is shown to an animal multiple times, the neural response will vary. In fact, the activity of a single neuron shows many features of a stochastic process. Furthermore, in the absence of a sensory stimulus, cortical spontaneous activity has a magnitude comparable to the activity observed during stimulus presentation. These findings have led to a widespread belief that neural activity is indeed very noisy. However, recent evidence indicates that individual neurons can operate very reliably and that the spontaneous activity in the brain is highly structured, suggesting that much of the noise may in fact be signal. One hypothesis regarding this putative signal is that it reflects a form of probabilistic inference through sampling. Here we show that the key features of neural variability can be accounted for in a completely deterministic network model through self-organization. As the network learns a model of its sensory inputs, the deterministic dynamics give rise to sampling-like inference. Our findings show that the notorious variability in neural recordings does not need to be seen as evidence for a noisy brain. Instead it may reflect sampling-like inference emerging from a self-organized learning process.

scholarly journals Cerebellar Golgi cell models predict dendritic processing and mechanisms of synaptic plasticity

2020 ◽  
Vol 16 (12) ◽  
pp. e1007937
Author(s):  
Stefano Masoli ◽  
Alessandra Ottaviani ◽  
Stefano Casali ◽  
Egidio D’Angelo
Keyword(s):  
Initial Segment ◽  
Calcium Influx ◽  
Spike Timing ◽  
Axon Initial Segment ◽  
Inhibitory Synapses ◽  
Golgi Cells ◽  
Basal Dendrites ◽  
Dendritic Processing ◽  
Dendritic Organization ◽  
Apical Dendrites

The Golgi cells are the main inhibitory interneurons of the cerebellar granular layer. Although recent works have highlighted the complexity of their dendritic organization and synaptic inputs, the mechanisms through which these neurons integrate complex input patterns remained unknown. Here we have used 8 detailed morphological reconstructions to develop multicompartmental models of Golgi cells, in which Na, Ca, and K channels were distributed along dendrites, soma, axonal initial segment and axon. The models faithfully reproduced a rich pattern of electrophysiological and pharmacological properties and predicted the operating mechanisms of these neurons. Basal dendrites turned out to be more tightly electrically coupled to the axon initial segment than apical dendrites. During synaptic transmission, parallel fibers caused slow Ca-dependent depolarizations in apical dendrites that boosted the axon initial segment encoder and Na-spike backpropagation into basal dendrites, while inhibitory synapses effectively shunted backpropagating currents. This oriented dendritic processing set up a coincidence detector controlling voltage-dependent NMDA receptor unblock in basal dendrites, which, by regulating local calcium influx, may provide the basis for spike-timing dependent plasticity anticipated by theory.

scholarly journals Noise-induced hyperactivity in the inferior colliculus: its relationship with hyperactivity in the dorsal cochlear nucleus

2012 ◽  
Vol 108 (4) ◽  
pp. 976-988 ◽  
Author(s):  
N. F. Manzoor ◽  
F. G. Licari ◽  
M. Klapchar ◽  
R. L. Elkin ◽  
Y. Gao ◽  
...  
Keyword(s):  
Spontaneous Activity ◽  
Inferior Colliculus ◽  
Cochlear Nucleus ◽  
Time Course ◽  
Noise Exposure ◽  
Dorsal Cochlear Nucleus ◽  
Control Group ◽  
Before And After ◽  
Intense Noise ◽  
And Control

Intense noise exposure causes hyperactivity to develop in the mammalian dorsal cochlear nucleus (DCN) and inferior colliculus (IC). It has not yet been established whether the IC hyperactivity is driven by hyperactivity from extrinsic sources that include the DCN or instead is maintained independently of this input. We have investigated the extent to which IC hyperactivity is dependent on input from the contralateral DCN by comparing recordings of spontaneous activity in the IC of noise-exposed and control hamsters before and after ablation of the contralateral DCN. One group of animals was binaurally exposed to intense sound (10 kHz, 115 dB SPL, 4 h), whereas the control group was not. Both groups were studied electrophysiologically 2–3 wk later by first mapping spontaneous activity along the tonotopic axis of the IC to confirm induction of hyperactivity. Spontaneous activity was then recorded at a hyperactive IC locus over two 30-min periods, one with DCNs intact and the other after ablation of the contralateral DCN. In a subset of animals, activity was again mapped along the tonotopic axis after the time course of the activity was recorded before and after DCN ablation. Following recordings, the brains were fixed, and histological evaluations were performed to assess the extent of DCN ablation. Ablation of the DCN resulted in major reductions of IC hyperactivity. Levels of postablation activity in exposed animals were similar to the levels of activity in the IC of control animals, indicating an almost complete loss of hyperactivity in exposed animals. The results suggest that hyperactivity in the IC is dependent on support from extrinsic sources that include and may even begin with the DCN. This finding does not rule out longer term compensatory or homeostatic adjustments that might restore hyperactivity in the IC over time.

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