Spike Frequency Adaptation In Neurons Research Articles

Theoretical analysis of effects of transcranial magneto-acoustical stimulation on neuronal spike-frequency adaptation

BackgroundTranscranial magneto-acoustical stimulation (TMAS) is a noninvasive technique that has advantages in spatial resolution and penetration depth. It changes the firing properties of neurons through the current generated by focused ultrasound and a static magnetic field. Spike-frequency adaptation is an important dynamic characteristic of neural information processing.MethodsTo address the effects of TMAS on neural spike-frequency adaptation, this study employs some ultrasound and magnetic field parameters, such as magnetic flux density, ultrasonic intensity, fundamental ultrasonic frequency, modulation frequency, and duty cycle. Using these different ultrasound and magnetic field parameters, membrane potential curves, spike-frequency curves, and adapted onset spike-frequency curves are exhibited and analyzed.ResultsThe results show that spike-frequency adaptation is strongly dependent on ultrasonic intensity and magnetic flux density and is rarely affected by other parameters. However, modulation frequency and duty cycle influence membrane potentials and spike frequencies to some degree.ConclusionsThis study reveals the mechanism of the effects of TMAS on neural spike-frequency adaptation and serves as theoretical guidance for TMAS experiments.

A Brain-Inspired Homeostatic Neuron Based on Phase-Change Memories for Efficient Neuromorphic Computing.

One of the main goals of neuromorphic computing is the implementation and design of systems capable of dynamic evolution with respect to their own experience. In biology, synaptic scaling is the homeostatic mechanism which controls the frequency of neural spikes within stable boundaries for improved learning activity. To introduce such control mechanism in a hardware spiking neural network (SNN), we present here a novel artificial neuron based on phase change memory (PCM) devices capable of internal regulation via homeostatic and plastic phenomena. We experimentally show that this mechanism increases the robustness of the system thus optimizing the multi-pattern learning under spike-timing-dependent plasticity (STDP). It also improves the continual learning capability of hybrid supervised-unsupervised convolutional neural networks (CNNs), in terms of both resilience and accuracy. Furthermore, the use of neurons capable of self-regulating their fire responsivity as a function of the PCM internal state enables the design of dynamic networks. In this scenario, we propose to use the PCM-based neurons to design bio-inspired recurrent networks for autonomous decision making in navigation tasks. The agent relies on neuronal spike-frequency adaptation (SFA) to explore the environment via penalties and rewards. Finally, we show that the conductance drift of the PCM devices, contrarily to the applications in neural network accelerators, can improve the overall energy efficiency of neuromorphic computing by implementing bio-plausible active forgetting.

Study of neuronal spike-frequency adaptation with transcranial magneto-acoustical stimulation

Transcranial magneto-acoustical stimulation (TMAS), utilizing focused ultrasound and a magnetostatic field to generate an electric current in tissue fluid to regulate the activities of neurons, has high spatial resolution and penetration depth. The neuronal spike-frequency adaptation plays an important role in the treatment of neural information. In this paper, we study the effects of ultrasonic intensity, magnetostatic field intensity and ultrasonic frequency on the neuronal spike-frequency adaptation based on the Ermentrout neuron model. The simulation results show that, the peak time interval becomes smaller, the interspike interval becomes shorter and the time of the firing of the neuron is shortened with the increasing of the magnetostatic field intensity. With the increase of the adaptive variables, the initial spike-frequency is shifted to the right with the magnetostatic field intensity, and the spike-frequency is linearly related to the increase of the magnetostatic field intensity in steady state. The simulation effect with change of the ultrasonic intensity is consistent with the change of magnetostatic field intensity. The change of the ultrasonic frequency has no effect on the neuronal spike-frequency adaptation. Under the different adaptive variables, with the increase of the adaptive variables, the initial spike-frequency amplitude decreased with the increasing of the ultrasonic frequency, and the spike-frequency is linearly related to the increase of the ultrasonic frequency in steady state. These results of the study can help us to reveal the mechanism of transcranial magneto-acoustical stimulation on the neuronal spike-frequency adaptation, and provide a theoretical basis for its application in the treatment of neurological disorders.

Spike Frequency Adaptation in Neurons of the Central Nervous System.

Neuronal firing patterns and frequencies determine the nature of encoded information of the neurons. Here we discuss the molecular identity and cellular mechanisms of spike-frequency adaptation in central nervous system (CNS) neurons. Calcium-activated potassium (KCa) channels such as BKCa and SKCa channels have long been known to be important mediators of spike adaptation via generation of a large afterhyperpolarization when neurons are hyper-activated. However, it has been shown that a strong hyperpolarization via these KCa channels would cease action potential generation rather than reducing the frequency of spike generation. In some types of neurons, the strong hyperpolarization is followed by oscillatory activity in these neurons. Recently, spike-frequency adaptation in thalamocortical (TC) and CA1 hippocampal neurons is shown to be mediated by the Ca2+-activated Cl- channel (CACC), anoctamin-2 (ANO2). Knockdown of ANO2 in these neurons results in significantly reduced spike-frequency adaptation accompanied by increased number of spikes without shifting the firing mode, which suggests that ANO2 mediates a genuine form of spike adaptation, finely tuning the frequency of spikes in these neurons. Based on the finding of a broad expression of this new class of CACC in the brain, it can be proposed that the ANO2-mediated spike-frequency adaptation may be a general mechanism to control information transmission in the CNS neurons.

Fast-onset long-term open-state block of sodium channels by A-type FHFs mediates classical spike accommodation in hippocampal pyramidal neurons.

Classical accommodation is a form of spike frequency adaptation in neurons whereby excitatory drive results in action potential output of gradually decreasing frequency. Here we describe an essential molecular component underlying classical accommodation in juvenile mouse hippocampal CA1 pyramidal neurons. A-type isoforms of fibroblast growth factor homologous factors (FHFs) bound to axosomatic voltage-gated sodium channels bear an N-terminal blocking particle that drives some associated channels into a fast-onset, long-term inactivated state. Use-dependent accumulating channel blockade progressively elevates spike voltage threshold and lengthens interspike intervals. The FHF particle only blocks sodium channels from the open state, and mutagenesis studies demonstrate that this particle uses multiple aliphatic and cationic residues to both induce and maintain the long-term inactivated state. The broad expression of A-type FHFs in neurons throughout the vertebrate CNS suggests a widespread role of these sodium channel modulators in the control of neural firing.

Odor segmentation and identification in an abstract large-scale model of the mammalian olfactory system

We integrate an olfactory epithelium and bulb (OB) model with an olfactory (piriform) cortex (OC) model, all comprising abstract graded units representing local populations of neurons, to demonstrate the overall system's applicability to odor recognition tasks. Large-scale simulations on a cluster computer allow us to evaluate an instance of the model with the size matching that of the olfactory system of a small mammal. The input data is synthesized with the intention to resemble the distribution of various features of early olfactory response patterns to naturalistic odor stimuli, e.g. [1,2]. Self-organization of the feedforward connectivity from the OB to the piriform cortex based on statistical properties of synthetic olfactory stimuli with the support of synaptic plasticity provide the capacity for generating sparse and distributed cortical representations [3]. At the cortical level, associative functions resulting from recurrent connectivity with Hebbian plasticity implement attractor memory storage and pattern processing, e.g. completion and rivalry [4]. Adaptation in cortical units, mimicking neuronal spike frequency adaptation, serves as an underlying mechanism for odor segmentation. We also investigate how backprojecting connections from the OC to the OB facilitate context dependent stimulus identification. The model is evaluated in real-world scenarios involving odor classification and segmentation in noisy environments. Firstly, the network is trained to perform concentration invariant odor recognition. Secondly, the model identifies single-ligand components of odor mixtures it is subjected to in a testing phase. Finally, the effect of context dependence is evaluated by examining the system's capability to recognize specific low intensity stimuli when it is forced into an arousal state. Preliminary results show the dependence of performance on the network size, the number of odors and the complexity of their early olfactory activation patterns. In a broader context, the proposed large-scale abstract models of holistic olfactory processing implements a multiscale approach to modeling olfaction. After the network has been trained, its connection matrices are utilized in simulating a more biophysically realistic model of the mammalian olfactory system (for details see poster by Kaplan et al.).

Ca 2+ Dependent Activation of Large Conductance Ca 2+ Activated Potassium (BK) Channels by Binding to the RCK1 Domain

BK channels sense intracellular Ca2+ and are important modulators of muscle contraction, neuronal spike frequency adaptation, neurotransmitter release and circadian pacemaker output. The cytosolic domain (CTD) of BK channels contains two structural sub-domains, RCK1 and RCK2. Mutagenesis studies have identified a series of Asp residues in the RCK2 domain (termed as the Ca2+ bowl) and Asp367 in the RCK1 domain as two putative Ca2+ binding sites. A recently published crystal structure of the BK CTD showed Ca2+ binding to the Ca2+ bowl but, surprisingly, provided less further information about the Ca2+ binding site in RCK1. We have performed mutational scan in the RCK1 domain to search for the residues that are necessary for Ca2+ binding in addition to Asp367. Here we show that the mutations of Glu535 in the RCK1 domain produce nearly identical functional consequences on the Ca2+ dependent activation as the mutations of Asp367. Therefore, Glu535, same as Asp367, may be one of binding coordinators for Ca2+ binding in RCK1. We also show that mutations of Met513, some of which have been previously shown to reduce Ca2+ sensitivity, result in a different pattern of functional consequences than those of Glu535 and Asp367, which suggest that Met513 is not part of the Ca2+ binding site. Molecular modeling and experimental data suggest that the binding of Ca2+ by the side chains of Glu535 and Asp367 changes the conformation around the binding site and turns the side chain of Met513 into a hydrophobic core, thereby opening the activation gate of BK channels. We have also investigated Cd2+ dependent activation of BK channels and found that Ca2+ and Cd2+ interact with different sets of residues to activate BK channels.

Modification of activation kinetics of delayed rectifier K+ currents and neuronal excitability by methyl-β-cyclodextrin

The effects of methyl-β-cyclodextrin (MβCD), an oligosaccharide, on ion currents were investigated in differentiated NG108-15 neuronal cells. In NG108-15 cells treated with dibutyryl cyclic AMP, the expression level of the KV3.1 mRNA was elevated. Depletion of membrane cholesterol by exposing cells to MβCD (1 mM) resulted in a significant reduction of the activation kinetics of delayed rectifier K+ current (IK(DR)) in these cells. However, neither activation nor inactivation curve of IK(DR) was altered following MβCD treatment. In current-clamp recordings, in MβCD-treated cells, the instantaneous frequency of the firing in response to long-lasting current stimuli was reduced. In a modified Hodgkin-Huxley neuron, the upward shift in the relationship of activation/deactivation time constant of IK(DR) versus membrane potential causes a reduction of IK(DR) amplitude accompanied by an increase in the width of action potentials. In the studies from a high-frequency modeled neuron, reduction of voltage-dependent activation of IK(DR) can also facilitate spike-frequency adaptation. In a simulated network of spiking neurons, the increased activation/deactivation time constant of IK(DR) slowed repetitive firing. Taken together, MβCD may slow activation kinetics of IK(DR) and confer a trigger for the propensity to develop spike-frequency adaptation in neurons or neuroendocrine cells.

Slow Spike Frequency Adaptation in Neurons of the Rat Subthalamic Nucleus

Neurons of the subthalamic nucleus (STN) are very sensitive to applied currents, firing at 10-20/s during spontaneous activity, but increasing to peak firing rates of 200/s with applied currents <0.5 nA. They receive a powerful tonic excitatory input from neurons in the cerebral cortex, yet in vivo maintain an irregular firing rate only slightly higher than the autonomous firing rate seen in slices. Spike frequency adaptation acts to normalize background firing rate by removing slow trends in firing due to changes in average input. Subthalamic neurons have been previously described as showing little spike frequency adaptation, but this was based on tests using brief stimuli. We applied long-duration depolarizing current steps to STN neurons in slices and observed a very strong spike frequency adaptation with a time constant of 20 s and that recovered at a similar rate. This adaptation could return firing to near-baseline levels during prolonged current pulses that transiently drove the cells at high rates. The current responsible for adaptation was studied in voltage clamp during and after high-frequency driving of the cell and was determined to be a slowly accumulating K(+) current. This current was independent of calcium or sodium entry and could be induced with long-duration voltage steps after blockade of action potentials. In addition to the adaptation current, driven firing produced slow inactivation of the persistent Na(+) current, which also contributed to the reduced excitability of STN cells during and after driven firing.

BK potassium channels facilitate high‐frequency firing and cause early spike frequency adaptation in rat CA1 hippocampal pyramidal cells

Neuronal potassium (K(+)) channels are usually regarded as largely inhibitory, i.e. reducing excitability. Here we show that BK-type calcium-activated K(+) channels enhance high-frequency firing and cause early spike frequency adaptation in neurons. By combining slice electrophysiology and computational modelling, we investigated functions of BK channels in regulation of high-frequency firing in rat CA1 pyramidal cells. Blockade of BK channels by iberiotoxin (IbTX) selectively reduced the initial discharge frequency in response to strong depolarizing current injections, thus reducing the early spike frequency adaptation. IbTX also blocked the fast afterhyperpolarization (fAHP), slowed spike rise and decay, and elevated the spike threshold. Simulations with a computational model of a CA1 pyramidal cell confirmed that the BK channel-mediated rapid spike repolarization and fAHP limits activation of slower K(+) channels (in particular the delayed rectifier potassium current (I(DR))) and Na(+) channel inactivation, whereas M-, sAHP- or SK-channels seem not to be important for the early facilitating effect. Since the BK current rapidly inactivates, its facilitating effect diminishes during the initial discharge, thus producing early spike frequency adaptation by an unconventional mechanism. This mechanism is highly frequency dependent. Thus, IbTX had virtually no effect at spike frequencies < 40 Hz. Furthermore, extracellular field recordings demonstrated (and model simulations supported) that BK channels contribute importantly to high-frequency burst firing in response to excitatory synaptic input to distal dendrites. These results strongly support the idea that BK channels play an important role for early high-frequency, rapidly adapting firing in hippocampal pyramidal neurons, thus promoting the type of bursting that is characteristic of these cells in vivo, during behaviour.

Differential Effects of Amino-Terminal Distal and Proximal Domains in the Regulation of Human erg K + Channel Gating

The participation of amino-terminal domains in human ether-a-go-go ( eag)- related gene (HERG) K + channel gating was studied using deleted channel variants expressed in Xenopus oocytes. Selective deletion of the HERG-specific sequence (HERG Δ138–373) located between the conserved initial amino terminus (the eag or PAS domain) and the first transmembrane helix accelerates channel activation and shifts its voltage dependence to hyperpolarized values. However, deactivation time constants from fully activated states and channel inactivation remain almost unaltered after the deletion. The deletion effects are equally manifested in channel variants lacking inactivation. The characteristics of constructs lacking only about half of the HERG-specific domain (Δ223–373) or a short stretch of 19 residues (Δ355–373) suggest that the role of this domain is not related exclusively to its length, but also to the presence of specific sequences near the channel core. Deletion-induced effects are partially reversed by the additional elimination of the eag domain. Thus the particular combination of HERG-specific and eag domains determines two important HERG features: the slow activation essential for neuronal spike-frequency adaptation and maintenance of the cardiac action potential plateau, and the slow deactivation contributing to HERG inward rectification.

Involvement of apamin-sensitive SK channels in spike frequency adaptation of neurons in nucleus tractus solitarii of the rat.

We delineated the role of Ca(2+)-activated K(+) channels in the phenomenon of spike frequency adaptation (SFA) exhibited by neurons in the caudal region of nucleus tractus solitarius (cNTS) using intracellular recording coupled with the current-clamp technique in rat brain slices. Intracellular injection of a constant depolarizing current evoked a train of action potentials whose discharge frequency declined rapidly to a lower steady-state level of irregular discharges. This manifested phenomenon of SFA was found to be related to extracellular Ca(2+). Low Ca(2+) (0.25 mM) or Cd(2+) (0.5 mM) in the perfusing medium resulted in a significant increase in the adaptation time constant (tau(adap)) and an appreciable reduction in the percentage adaptation of spike frequency (F(adap)). In addition, the evoked discharges were converted from an irregular to a regular pattern, accompanied by a profound increase in mean firing rate. Intriguingly, similar alterations in tau(adap), F(adap), discharge pattern and discharge rate were elicited by apamin (1 microM), a selective blocker for small-conductance Ca(2+)-activated K(+) (SK) channels. On the other hand, charybdotoxin (0.1 microM), a selective blocker for large-conductance Ca(2+)-activated K(+) channels, was ineffective. Our results suggest that SK channels of cNTS neurons may subserve the generation of both SFA and irregular discharge patterns displayed by action potentials evoked with a prolonged depolarizing current.

Involvement of Apamin-Sensitive SK Channels in Spike Frequency Adaptation of Neurons in Nucleus tractus solitarii of the Rat

We delineated the role of Ca²⁺-activated K⁺ channels in the phenomenon of spike frequency adaptation (SFA) exhibited by neurons in the caudal region of nucleus tractus solitarius (cNTS) using intracellular recording coupled with the current-clamp technique in rat brain slices. Intracellular injection of a constant depolarizing current evoked a train of action potentials whose discharge frequency declined rapidly to a lower steady-state level of irregular discharges. This manifested phenomenon of SFA was found to be related to extracellular Ca²⁺. Low Ca²⁺ (0.25 mM) or Cd²⁺ (0.5 mM) in the perfusing medium resulted in a significant increase in the adaptation time constant (τ_adap) and an appreciable reduction in the percentage adaptation of spike frequency (F_adap). In addition, the evoked discharges were converted from an irregular to a regular pattern, accompanied by a profound increase in mean firing rate. Intriguingly, similar alterations in τ_adap, F_adap, discharge pattern and discharge rate were elicited by apamin (1 μM), a selective blocker for small-conductance Ca²⁺-activated K⁺ (SK) channels. On the other hand, charybdotoxin (0.1 μM), a selective blocker for large-conductance Ca²⁺-activated K⁺ channels, was ineffective. Our results suggest that SK channels of cNTS neurons may subserve the generation of both SFA and irregular discharge patterns displayed by action potentials evoked with a prolonged depolarizing current.