scholarly journals Axonal Na+ channels detect and transmit levels of input synchrony in local brain circuits

2019 ◽  
Author(s):  
Mickaёl Zbili ◽  
Sylvain Rama ◽  
Pierre Yger ◽  
Yanis Inglebert ◽  
Norah Boumedine-Guignon ◽  
...  
Keyword(s):  
Sodium Channels ◽  
Sensory Processing ◽  
Coincidence Detection ◽  
Network Activity ◽  
Spike Threshold ◽  
Brain Circuits ◽  
Presynaptic Spike ◽  
Cortical Synapses ◽  
Powerful Mechanism ◽  
Local Brain

AbstractSensory processing requires mechanisms of fast coincidence-detection to discriminate synchronous from asynchronous inputs. Spike-threshold adaptation enables such a discrimination but is ineffective in transmitting this information to the network. We show here that presynaptic axonal sodium channels read and transmit precise levels of input synchrony to the postsynaptic cell by modulating the presynaptic action potential (AP) amplitude. As a consequence, synaptic transmission is facilitated at cortical synapses when the presynaptic spike is produced by synchronous inputs. Using dual soma-axon recordings, imaging, and modeling, we show that this facilitation results from enhanced AP amplitude in the axon due to minimized inactivation of axonal sodium-channels. Quantifying local circuit activity and using network modeling, we found that spikes induced by synchronous inputs produced a larger effect on network activity than spikes induced by asynchronous inputs. Therefore, this input-synchrony dependent facilitation (ISF) may constitute a powerful mechanism regulating spike transmission.

scholarly journals Axonal Na+ channels detect and transmit levels of input synchrony in local brain circuits

2020 ◽  
Vol 6 (19) ◽  
pp. eaay4313 ◽  
Author(s):  
Mickaël Zbili ◽  
Sylvain Rama ◽  
Pierre Yger ◽  
Yanis Inglebert ◽  
Norah Boumedine-Guignon ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Sodium Channels ◽  
Sensory Processing ◽  
Coincidence Detection ◽  
Network Activity ◽  
Brain Circuits ◽  
Presynaptic Spike ◽  
Cortical Synapses ◽  
Powerful Mechanism ◽  
Local Brain

Sensory processing requires mechanisms of fast coincidence detection to discriminate synchronous from asynchronous inputs. Spike threshold adaptation enables such a discrimination but is ineffective in transmitting this information to the network. We show here that presynaptic axonal sodium channels read and transmit precise levels of input synchrony to the postsynaptic cell by modulating the presynaptic action potential (AP) amplitude. As a consequence, synaptic transmission is facilitated at cortical synapses when the presynaptic spike is produced by synchronous inputs. Using dual soma-axon recordings, imaging, and modeling, we show that this facilitation results from enhanced AP amplitude in the axon due to minimized inactivation of axonal sodium channels. Quantifying local circuit activity and using network modeling, we found that spikes induced by synchronous inputs produced a larger effect on network activity than spikes induced by asynchronous inputs. Therefore, this input synchrony–dependent facilitation may constitute a powerful mechanism, regulating synaptic transmission at proximal synapses.

scholarly journals Mining the Virgin Land of Neurotoxicology: A Novel Paradigm of Neurotoxic Peptides Action on Glycosylated Voltage-Gated Sodium Channels

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Zhirui Liu ◽  
Jie Tao ◽  
Pin Ye ◽  
Yonghua Ji
Keyword(s):  
Sodium Channels ◽  
Network Activity ◽  
Voltage Gated ◽  
Virgin Land ◽  
Neuronal Network Activity ◽  
Voltage Gated Sodium Channels ◽  
Pharmacological Targets ◽  
Underlying Mechanisms ◽  
Posttranslation Modification

Voltage-gated sodium channels (VGSCs) are important membrane protein carrying on the molecular basis for action potentials (AP) in neuronal firings. Even though the structure-function studies were the most pursued spots, the posttranslation modification processes, such as glycosylation, phosphorylation, and alternative splicing associating with channel functions captured less eyesights. The accumulative research suggested an interaction between the sialic acids chains and ion-permeable pores, giving rise to subtle but significant impacts on channel gating. Sodium channel-specific neurotoxic toxins, a family of long-chain polypeptides originated from venomous animals, are found to potentially share the binding sites adjacent to glycosylated region on VGSCs. Thus, an interaction between toxin and glycosylated VGSC might hopefully join the campaign to approach the role of glycosylation in modulating VGSCs-involved neuronal network activity. This paper will cover the state-of-the-art advances of researches on glycosylation-mediated VGSCs function and the possible underlying mechanisms of interactions between toxin and glycosylated VGSCs, which may therefore, fulfill the knowledge in identifying the pharmacological targets and therapeutic values of VGSCs.

scholarly journals Oxytocin shapes spontaneous activity patterns in the developing visual cortex by activating somatostatin interneurons

2019 ◽  
Author(s):  
Paloma P Maldonado ◽  
Alvaro Nuno-Perez ◽  
Jan Kirchner ◽  
Elizabeth Hammock ◽  
Julijana Gjorgjieva ◽  
...  
Keyword(s):  
Visual Cortex ◽  
Spontaneous Activity ◽  
Sensory Processing ◽  
Activity Patterns ◽  
Network Activity ◽  
Synaptic Connections ◽  
Pairwise Correlations ◽  
Early Brain Development

SummarySpontaneous network activity shapes emerging neuronal circuits during early brain development, however how neuromodulation influences this activity is not fully understood. Here, we report that the neuromodulator oxytocin powerfully shapes spontaneous activity patterns. In vivo, oxytocin strongly decreased the frequency and pairwise correlations of spontaneous activity events in visual cortex (V1), but not in somatosensory cortex (S1). This differential effect was a consequence of oxytocin only increasing inhibition in V1 and increasing both inhibition and excitation in S1. The increase in inhibition was mediated by the depolarization and increase in excitability of somatostatin+ (SST) interneurons specifically. Accordingly, silencing SST+ neurons pharmacogenetically fully blocked oxytocin’s effect on inhibition in vitro as well its effect on spontaneous activity patterns in vivo. Thus, oxytocin decreases the excitatory/inhibitory ratio and modulates specific features of V1 spontaneous activity patterns that are crucial for refining developing synaptic connections and sensory processing later in life.

Downregulation of sodium channels during anoxia: a putative survival strategy of turtle brain

1992 ◽  
Vol 262 (4) ◽  
pp. R712-R715 ◽  
Author(s):  
M. A. Perez-Pinzon ◽  
M. Rosenthal ◽  
T. J. Sick ◽  
P. L. Lutz ◽  
J. Pablo ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Sodium Channels ◽  
Tissue Oxygenation ◽  
Mammalian Brain ◽  
Survival Strategy ◽  
Voltage Gated ◽  
Channel Density ◽  
Spike Threshold ◽  
Channel Arrest ◽  
Key Factor

In contrast to mammalian brain, which exhibits rapid degeneration during anoxia, the brains of certain species of turtles show an extraordinary capacity to survive prolonged anoxia. The decrease in energy expenditure shown by the anoxic turtle brain is likely to be a key factor for anoxic survival. The "channel arrest" hypothesis proposes that ion channels, which regulate brain electrical activity in normoxia, may be altered during anoxia in the turtle brain as a mechanism to spare energy. Goals of present research were to test this hypothesis and to determine whether down-regulation of sodium channels is a possible explanation for spike threshold shifts seen during anoxia in isolated turtle cerebellum. We report here that anoxia induced a significant (42%) decline in voltage-gated sodium channel density as determined by studies of the binding of a sodium channel ligand, [3H]brevetoxin. This study demonstrates that sodium channel densities in brain may be regulated by tissue oxygenation or by physiological events associated with anoxia. Moreover, it also suggests that downregulation of sodium channels may be a basis for changes in action potential thresholds, the electrical depression and energy conservation that provide the unique anoxic tolerance of turtle brain.

scholarly journals Extracellular GABA waves regulate coincidence detection in excitatory circuits

2020 ◽  
Author(s):  
Sergiy Sylantyev ◽  
Leonid P. Savtchenko ◽  
Nathanael O’Neill ◽  
Dmitri A. Rusakov
Keyword(s):  
Strong Dependence ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Underlying Mechanism ◽  
Brain Network ◽  
Coincidence Detection ◽  
Network Activity ◽  
Gaba Uptake ◽  
Signal Integration ◽  
Feed Forward

AbstractCoincidence detection of excitatory inputs by principal neurons underpins the rules of signal integration and Hebbian plasticity in the brain. In the hippocampal circuitry, detection fidelity is thought to depend on the GABAergic synaptic input through a feed-forward inhibitory circuit also involving the hyperpolarization-activated Ih current. However, afferent connections often bypass feed-forward circuitry, suggesting that a different GABAergic mechanism might control coincidence detection in such cases. To test whether fluctuations in the extracellular GABA concentration [GABA] could play a regulatory role here, we use a GABA ‘sniffer’ patch in acute hippocampal slices of the rat and document strong dependence of [GABA] on network activity. We find that blocking GABAergic signalling strongly reduces the coincidence detection window of direct excitatory inputs to pyramidal cells whereas increasing [GABA] through GABA uptake blockade expands it. The underlying mechanism involves membrane-shunting tonic GABAA receptor current; it does not have to rely on Ih but depends strongly on the neuronal GABA transporter GAT-1. We use dendrite-soma dual patch-clamp recordings to show that the strong effect of membrane shunting on coincidence detection relies on nonlinear amplification of changes in the decay of dendritic synaptic currents when they reach the soma. Our results suggest that, by dynamically regulating extracellular GABA, brain network activity can optimise signal integration rules in local excitatory circuits.

scholarly journals Hierarchical cross-scale analysis identifies parallel ventral striatal networks coding for dynamic and stabilized olfactory reward predictions

2021 ◽  
Author(s):  
Laurens Winkelmeier ◽  
Carla Filosa ◽  
Max Scheller ◽  
Renée Hartig ◽  
Markus Sack ◽  
...  
Keyword(s):  
Functional Differentiation ◽  
Network Activity ◽  
Olfactory Conditioning ◽  
Neuronal Populations ◽  
Brain Circuits ◽  
Reward Prediction ◽  
History Of ◽  
Transient Network ◽  
Uncertain Outcomes ◽  
Prediction Coding

SUMMARYThe unbiased identification of brain circuits responsible for behavior and their local cellular computations is a challenge for neuroscience. We establish here a hierarchical cross-scale approach from behavioral modeling and fMRI in task-performing mice to cellular network dynamics to identify how reward predictions are represented in the forebrain upon olfactory conditioning. fMRI identified functional segregation in reward prediction and error computations among olfactory cortices and subcortical circuits. Among them, the olfactory tubercle contributed both to dynamic reward predictions and prediction error. In this region, cellular recordings revealed two parallel neuronal populations for prediction coding. One population produced stabilized predictions as distributed stimulus-bound transient network activity; the other evolved during anticipatory waiting and fully reflected predicted value in single-units, dynamically integrating the recent cue-specific history of uncertain outcomes. Thus, the cross-scale approach revealed regional functional differentiation among the distributed forebrain circuits with a limbic hotspot for multiple non-redundant reward prediction coding.

scholarly journals Neocortex Network Activation and Deactivation States Controlled by the Thalamus

2010 ◽  
Vol 103 (3) ◽  
pp. 1147-1157 ◽  
Author(s):  
Akio Hirata ◽  
Manuel A. Castro-Alamancos
Keyword(s):  
Brain Stem ◽  
Sensory Processing ◽  
Basal Forebrain ◽  
Barrel Cortex ◽  
Sensory Information ◽  
Network Activity ◽  
Tonic Firing ◽  
Network Activation ◽  
Activated State

Neocortex network activity varies from a desynchronized or activated state typical of arousal to a synchronized or deactivated state typical of quiescence. Such changes are usually attributed to the effects of neuromodulators released in the neocortex by nonspecific activating systems originating in basal forebrain and brain stem reticular formation. As a result, the only role attributed to thalamocortical cells projecting to primary sensory areas, such as barrel cortex, is to transmit sensory information. However, thalamocortical cells can undergo significant changes in spontaneous tonic firing as a function of state, although the role of such variations is unknown. Here we show that the tonic firing level of thalamocortical cells, produced by cholinergic and noradrenergic stimulation of the somatosensory thalamus in urethane-anesthetized rats, controls neocortex activation and deactivation. Thus in addition to its well-known role in the relay of sensory information, the thalamus can control the state of neocortex activation, which may complement the established roles in this regard of basal forebrain and brain stem nuclei. Because of the topographical organization of primary thalamocortical pathways, this mechanism provides a means by which area-specific neocortical activation can occur, which may be useful for modality-specific sensory processing or selective attention.

scholarly journals Subhypnotic Doses of Isoflurane Impair Auditory Discrimination in Rats

2007 ◽  
Vol 106 (4) ◽  
pp. 754-762 ◽  
Author(s):  
Rita H. Burlingame ◽  
Sneha Shrestha ◽  
Michael R. Rummel ◽  
Matthew I. Banks
Keyword(s):  
Sensory Processing ◽  
Stimulus Pair ◽  
Auditory Processing ◽  
Time Trial ◽  
Auditory Pathway ◽  
Auditory Discrimination ◽  
Network Activity ◽  
Neural Responses ◽  
Short Stimulus ◽  
And Performance

Background Isoflurane at subhypnotic doses is known to affect cellular and network activity in the auditory pathway, but the behavioral effects of these concentrations of isoflurane on auditory processing have not been tested previously. The authors tested the hypothesis that subhypnotic doses of isoflurane would impair auditory discrimination in rats. Methods Rats were tested on their ability to discriminate up versus down frequency-modulated sweeps using three different pairs of sweeps ("Long," "Med," "Short"), whose frequency range and duration were varied systematically to make the discrimination more difficult. Rats were tested daily in the absence and presence of isoflurane at 0.2% or 0.4%. The effects of isoflurane (0%, 0.2%, and 0.4%) on performance (= % correct) and efficiency (= time/trial) were assessed using regression analysis. Results The effect of isoflurane was stimulus-dependent: performance for the Long stimulus pair was unaffected by isoflurane, performance on the Med stimulus pair was impaired only by 0.4% isoflurane, and performance on the Short stimulus pair was impaired by both 0.2% and 0.4% isoflurane. In contrast, isoflurane decreased efficiency equally for all stimulus pairs at 0.4% and had no effect at 0.2%. Conclusions The stimulus dependence of the effect of isoflurane on performance suggests that it is unlikely this effect was secondary to effects on memory, motivation, or motor function. These data indicate that doses of isoflurane known to produce modest effects on neural responses alter cortical sensory processing.

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