scholarly journals Dynamic-Clamp Analysis of the Effects of Convergence on Spike Timing. II. Few Synaptic Inputs

2005 ◽  
Vol 94 (4) ◽  
pp. 2526-2534 ◽  
Author(s):  
Matthew A. Xu-Friedman ◽  
Wade G. Regehr

Sensory pathways in the nervous system possess mechanisms for decreasing spike-timing variability (“jitter”), probably to increase acuity. Most studies of jitter reduction have focused on convergence of many subthreshold inputs. However, many neurons receive only a few active inputs at any given time, and jitter reduction under these conditions is not well understood. We examined this issue using dynamic-clamp recordings in slices from mouse auditory brain stem. Significant jitter reduction was possible with as few as two inputs, provided the inputs had several features. First, jitter reduction was greatest and most reliable for supra-threshold inputs. Second, significant jitter reduction occurred when the distribution of input times had a rapid onset, i.e., for alpha- but not for Gaussian-distributed inputs. Third, jitter reduction was compromised unless late inputs were suppressed by the refractory period of the cell. These results contrast with the finding in the previous paper in which many subthreshold inputs contribute to jitter reduction, whether alpha- or Gaussian-distributed. In addition, convergence of many subthreshold inputs could fail to elicit any postsynaptic response when the input distribution outlasted the refractory period of the cell. These significant differences indicate that each means of reducing jitter has advantages and disadvantages and may be more effective for different neurons depending on the properties of their inputs.

2005 ◽  
Vol 94 (4) ◽  
pp. 2512-2525 ◽  
Author(s):  
Matthew A. Xu-Friedman ◽  
Wade G. Regehr

Precise action potential timing is crucial in sensory acuity and motor control. Convergence of many synaptic inputs is thought to provide a means of decreasing spike-timing variability (“jitter”), but its effectiveness has never been tested in real neurons. We used the dynamic-clamp technique in mouse auditory brain stem slices to examine how convergence controls spike timing. We tested the roles of several synaptic properties that are influenced by ongoing activity in vivo: the number of active inputs ( N), their total synaptic conductance ( Gtot), and their timing, which can resemble an alpha or a Gaussian distribution. Jitter was reduced most with large N, up to a factor of over 20. Variability in N is likely to occur in vivo, but this added little jitter. Jitter reduction also depended on the timing of inputs: alpha-distributed inputs were more effective than Gaussian-distributed inputs. Furthermore, the two distributions differed in their sensitivity to synaptic conductance: for Gaussian-distributed inputs, jitter was most reduced when Gtot was 2–3 times threshold, whereas alpha-distributed inputs showed continued jitter reduction with higher Gtot. However, very high Gtot caused the postsynaptic cell to fire multiple times, particularly when the input jitter outlasted the cell's refractory period, which interfered with jitter reduction. Gtot also greatly affected the response latency, which could influence downstream computations. Changes in Gtot are likely to arise in vivo through activity-dependent changes in synaptic strength. High rates of postsynaptic activity increased the number of synaptic inputs required to evoke a postsynaptic response. Despite this, jitter was still effectively reduced, particularly in cases when this increased threshold eliminated secondary spikes. Thus these studies provide insight into how specific features of converging inputs control spike timing.


Author(s):  
C.J. Wilson

Most central nervous system neurons receive synaptic input from hundreds or thousands of other neurons, and the computational function of such neurons results from the interactions of inputs on a large and complex scale. In most situations that have yielded to a partial analysis, the synaptic inputs to a neuron are not alike in function, but rather belong to distinct categories that differ qualitatively in the nature of their effect on the postsynaptic cell, and quantitatively in the strength of their influence. Many factors have been demonstrated to contribute to synaptic function, but one of the simplest and best known of these is the geometry of the postsynaptic neuron. The fundamental nature of the relationship between neuronal shape and synaptic effectiveness was established on theoretical grounds prior to its experimental verification.


2015 ◽  
Vol 25 (07) ◽  
pp. 1540005
Author(s):  
Ilya Prokin ◽  
Ivan Tyukin ◽  
Victor Kazantsev

The work investigates the influence of spike-timing dependent plasticity (STDP) mechanisms on the dynamics of two synaptically coupled neurons driven by additive external noise. In this setting, the noise signal models synaptic inputs that the pair receives from other neurons in a larger network. We show that in the absence of STDP feedbacks the pair of neurons exhibit oscillations and intermittent synchronization. When the synapse connecting the neurons is supplied with a phase selective feedback mechanism simulating STDP, induced dynamics of spikes in the coupled system resembles a phase locked mode with time lags between spikes oscillating about a specific value. This value, as we show by extensive numerical simulations, can be set arbitrary within a broad interval by tuning parameters of the STDP feedback.


1999 ◽  
Vol 202 (2) ◽  
pp. 103-113 ◽  
Author(s):  
R.M. Johnston ◽  
C. Consoulas ◽  
H. Pflüger ◽  
R.B. Levine

The unpaired median neurons are common to the segmental ganglia of many insects. Although some of the functional consequences of their activation, among them the release of octopamine to modulate muscle contraction, have been described, less is understood about how and when these neurons are recruited during movement. The present study demonstrates that peripherally projecting unpaired median neurons in the abdominal and thoracic ganglia of the larval tobacco hornworm Manduca sexta are recruited rhythmically during the fictive crawling motor activity that is produced by the isolated central nervous system in response to pilocarpine. Regardless of the muscles to which they project, the efferent unpaired median neurons in all segmental ganglia are depolarized together during the phase of the crawling cycle when the thoracic leg levator motoneurons are active. During fictive crawling, therefore, the unpaired median neurons are not necessarily active in synchrony with the muscles to which they project. The rhythmical synaptic drive of the efferent unpaired median neurons is derived, at least in part, from a source within the subesophageal ganglion, even when the motor pattern is evoked by exposing only the more posterior ganglia to pilocarpine. In pairwise intracellular recordings from unpaired median neurons in different ganglia, prominent excitatory postsynaptic potentials, which occur with an anterior-to-posterior delay in both neurons, are seen to underlie the rhythmic depolarizations. One model consistent with these findings is that one or more neurons within the subesophageal ganglion, which project posteriorly to the segmental ganglia and ordinarily provide unpatterned synaptic inputs to all efferent unpaired median neurons, become rhythmically active during fictive crawling in response to ascending information from the segmental pattern-generating network.


Cephalalgia ◽  
1981 ◽  
Vol 1 (4) ◽  
pp. 209-216 ◽  
Author(s):  
David Russell

A detailed clinical study of 77 spontaneous cluster headache attacks has been carried out. The information was recorded during a period when patients were without medication and with the use of methods which were not dependent on the patients' memory of events. The findings stress the usual rapid onset and termination of attacks, and their short duration. There was a preponderance of attacks beginning during sleep and the majority of daytime attacks began when patients were physically relaxed. No significant difference between nocturnal and daytime attacks was found as regards severity or temporal profiles. A significant positive correlation was found between severity of maximal pain and both duration of maximal pain and total duration of attacks. “Abortive attacks” accounted for 16% of attacks. The apparent spontaneous arrest of these attacks does not appear to be due to special features of patient activity prior to or during attacks, nor are they restricted to a refractory period following more severe attacks.


Part of the Oxford Textbooks in Clinical Neurology series, the Oxford Textbook of Neuromuscular Disorders covers the scientific basis, clinical diagnosis, and treatment of neuromuscular disorders with a particular focus on the most clinically relevant disorders. The resource is organized into seven sections, starting with the general approach to the patient with neuromuscular disorders and then focusing on specific neuromuscular conditions affecting the peripheral nervous system from its origins at the spinal cord anterior horn on its outward course to their effector muscles and the inbound sensory pathways. Chapters on specific neuromuscular conditions are illustrated with typical case histories and their presenting features, allowing readers to put rarer conditions into their clinical context more easily.


2009 ◽  
Vol 102 (5) ◽  
pp. 2627-2637 ◽  
Author(s):  
Lioudmila Pliss ◽  
Hua Yang ◽  
Matthew A. Xu-Friedman

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.


2009 ◽  
Vol 102 (3) ◽  
pp. 1699-1710 ◽  
Author(s):  
Hua Yang ◽  
Matthew A. Xu-Friedman

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.


Neuroscience ◽  
2004 ◽  
Vol 126 (4) ◽  
pp. 1063-1073 ◽  
Author(s):  
A Szűcs ◽  
Á Vehovszky ◽  
G Molnár ◽  
R.D Pinto ◽  
H.D.I Abarbanel

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