Discharge Patterns Of Neurons Research Articles

Human sympathetic neuronal discharge and recruitment patterns regulate neuropeptide Y bioavailability.

What is the purpose of sympathetic neuronal action potential (AP) discharge and recruitment patterns for human vascular regulation? This study tested the hypothesis that sympathetic neuronal discharge and recruitment patterns regulate neuropeptide Y (NPY) bioavailability. We used microneurography to record muscle sympathetic nerve activity (MSNA) and a continuous wavelet transform to detect sympathetic APs during a baseline condition and intravenous dexmedetomidine infusion (α2-adrenergic agonist, 10 min loading infusion of 0.225 µg kg-1; maintenance infusion of 0.1-0.5 µg kg h-1) in six healthy individuals (5 females, 27 ± 6 years). Arterial blood samples provided NPY (enzyme-linked immunosorbent assay) and norepinephrine (Liquid Chromatography Tandem Mass Spectrometry) levels during baseline and the dexmedetomidine maintenance infusion. Linear mixed model regressions assessed the relationships between AP discharge, recruitment, and neurotransmitter levels. Across baseline and the dexmedetomidine condition, NPY levels were positively related to mean arterial pressure (β = 1.63 [0.34], P = 0.002), total AP clusters (β = 0.90 [0.22], P = 0.005), and AP frequency (β = 0.11 [0.03], P = 0.003). Norepinephrine levels were not related to mean arterial pressure (β = 0.03 [0.02], P = 0.133) but were positively related to total AP clusters (β = 19.50 [7.07], P = 0.030) and AP frequency (β = 2.66 [0.81], P = 0.014). These data suggest that sympathetic neuronal discharge and recruitment patterns regulate NPY and norepinephrine bioavailability in healthy adults. As such, sympathetic neuronal firing strategies are important for human vascular regulation.

A Novel Coupled Memristive Izhikevich Neuron Model and Its Complex Dynamics

This paper proposes a novel, five-dimensional memristor synapse-coupled Izhikevich neuron model under electromagnetic induction. Firstly, we analyze the global exponential stability of the presented system by constructing an appropriate Lyapunov function. Furthermore, the Hamilton energy functions of the model and its corresponding error system are derived by using Helmholtz’s theorem. In addition, the influence of external current and system parameters on the dynamical behavior are investigated. The numerical simulation results indicate that the discharge pattern of excitatory and inhibitory neurons changes significantly when the amplitude and frequency of the external stimulus current are applied at different degrees. And the crucial dynamical behavior of the neuronal system is determined by the intensity of modulation of the induced current and the gain in the electromagnetic induction. Moreover, the amount of Hamilton energy released by the model could be evaluated during the conversion between the distinct dynamical behaviors.

Dorsal and median raphe neuronal firing dynamics characterized by nonlinear measures.

The dorsal (DRN) and median (MRN) raphe are important nuclei involved in similar functions, including mood and sleep, but playing distinct roles. These nuclei have a different composition of neuronal types and set of neuronal connections, which among other factors, determine their neuronal dynamics. Most works characterize the neuronal dynamics using classic measures, such as using the average spiking frequency (FR), the coefficient of variation (CV), and action potential duration (APD). In the current study, to refine the characterization of neuronal firing profiles, we examined the neurons within the raphe nuclei. Through the utilization of nonlinear measures, our objective was to discern the redundancy and complementarity of these measures, particularly in comparison with classic methods. To do this, we analyzed the neuronal basal firing profile in both nuclei of urethane-anesthetized rats using the Shannon entropy (Bins Entropy) of the inter-spike intervals, permutation entropy of ordinal patterns (OP Entropy), and Permutation Lempel-Ziv Complexity (PLZC). Firstly, we found that classic (i.e., FR, CV, and APD) and nonlinear measures fail to distinguish between the dynamics of DRN and MRN neurons, except for the OP Entropy. We also found strong relationships between measures, including the CV with FR, CV with Bins entropy, and FR with PLZC, which imply redundant information. However, APD and OP Entropy have either a weak or no relationship with the rest of the measures tested, suggesting that they provide complementary information to the characterization of the neuronal firing profiles. Secondly, we studied how these measures are affected by the oscillatory properties of the firing patterns, including rhythmicity, bursting patterns, and clock-like behavior. We found that all measures are sensitive to rhythmicity, except for the OP Entropy. Overall, our work highlights OP Entropy as a powerful and useful quantity for the characterization of neuronal discharge patterns.

Spike Dynamics Analysis in Semiconductor Ring Laser

In this paper, a method of generating controllable spikes utilizing symmetric semiconductor ring lasers (SRLs) is investigated, and various optical behaviors of biological neurons are successfully emulated on a faster timescale. We demonstrate the synchronized spike phenomena in two directions, generated in both the clockwise (CW) and counterclockwise (CCW) modes of the tunable laser (TL)-injected SRL. The size of the peaks and the interval between them can be manipulated by adjusting the output complex amplitude of the TL and bias current. At the same time, we also analyzed the CW mode of the TL-injected SRL and successfully replicated the four distinct discharge patterns of biological neurons. These findings offer promising prospects for future neuromorphic research.

Resilience of FEF neuronal saccade code to V4 perturbations.

The frontal eye field (FEF) plays a key role in initiating rapid eye movements known as saccades. Accumulation models have been proposed to explain the dynamic of these neurons and how they may enable the initiation of saccades. To update the scope of the viability of this model, we studied single neurons recorded from the FEF of two rhesus monkeys while they performed a memory-guided saccade task. We evaluated the degree to which each type of FEF neuron complied with these models by quantifying how precisely their discharge predicted an imminent saccade based on their immediate presaccadic activity. We found that decoders trained on single neurons with a stronger motor component performed better than decoders trained on neurons with a stronger visual component in predicting the saccade. Importantly, despite a dramatic effect on the reaction times, the perturbations delivered to the FEF neurons via area V4 did not impact their saccade predictability. Our results demonstrate a high degree of resilience of the FEF neuronal presaccadic discharge patterns, fulfilling the predictions of accumulation models.NEW & NOTEWORTHY We studied neurons in the brain's frontal eye field (FEF) to understand how these neurons predict swift eye shifts called saccades. We found that neurons with more movement-related activity were better at predicting saccades than those with sensory-related activity. Interestingly, electrical disruptions of this region strongly impacted saccade onset times but did not affect the individual neuron's saccade predictability, consistent with models suggesting that a specific threshold in neural activity triggers the saccade.

Central alpha-2 adrenergic mechanisms affect human sympathetic neuronal discharge strategies

The central neural mechanisms affecting sympathetic neuronal discharge strategies supporting homeostatic adjustments in human muscle sympathetic nerve activity (MSNA) remain unclear. This study investigated the hypothesis that central alpha-2 adrenergic mechanisms affect sympathetic action potential (AP) discharge, recruitment, and latency patterns within human MSNA (peroneal nerve microneurography and continuous wavelet transform). An alpha-2 adrenergic agonist (dexmedetomidine) was infused in eight healthy male and female participants (5 females; 28 ± 7years). Data were recorded during a 5-minute resting control condition, a 10-minute intravenous dexmedetomidine loading dose (0.225 μg/kg), and a dexmedetomidine maintenance dose (~0.1 μg/kg/hr). Data are reported as mean (SD) for the 5-minute control condition and 2-minutes of the dexmedetomidine infusion when MSNA bursting activity was demonstrably reduced. Two-tailed paired t-tests were performed. Dexmedetomidine reduced mean pressure (92 ± 7 to 80 ± 8 mmHg; P < 0.01) but did not affect heart rate (61 ± 13 to 60 ± 14 bpm; P = 0.75). Dexmedetomidine reduced integrated MSNA burst frequency (14 ± 6 to 4 ± 3 bursts/min; P < 0.01), sympathetic AP frequency (75 ± 46 to 16 ± 14 AP/min; P < 0.01), APs per burst (5 ± 1 to 4 ± 1 AP/burst; P = 0.01), AP clusters per burst (3.5 ± 0.7 to 3.0 ± 0.7 clusters/burst; P = 0.03), and de-recruited the largest AP clusters (12 ± 3 to 7 ± 2 AP clusters; P < 0.01). Despite de-recruiting large AP clusters with short conduction times, dexmedetomidine elicited shorter sympathetic AP conduction times (1.18 ± 0.12 to 1.14 ± 0.13 s; P = 0.03). Six participants performed a Valsalva Maneuver (20 s, 40 mmHg mouth pressure) during the control condition and during the dexmedetomidine maintenance dose. Data are reported as mean (SD) change (Δ) from the 2-minute period preceding the Valsalva Maneuver to the Valsalva Maneuver for each condition. During the control condition, Valsalva Maneuver increased AP frequency (Δ 311 ± 317 AP/min; P = 0.048), recruited larger previously silent AP clusters (Δ 2 ± 1 AP clusters; P < 0.01), and elicited shorter AP conduction times (Δ ‑0.09 ± 0.07 s; P = 0.02). Compared to the control condition, Valsalva Maneuver performed during the dexmedetomidine maintenance dose condition elicited lesser increases in AP frequency (Δ 116 ± 189 AP/min; P vs. control = 0.02) and lesser recruitment of larger previously silent AP clusters (Δ 0 ± 1 AP clusters; P vs. control = 0.02). Dexmedetomidine did not affect the latency reduction elicited by Valsalva Maneuver (Δ ‑0.07 ± 0.14 s; P vs. control = 0.61). These data suggest that human central alpha-2 adrenergic mechanisms affect: i) sympathetic postganglionic neuronal discharge and recruitment patterns, and ii) synaptic delays within the sympathetic neurocircuitry influencing AP latency. This work was supported by the Natural Sciences and Engineering Research Council of Canada (NSERC) and the National Institutes of Health (NIH). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Locus Coeruleus Neurons’ Firing Pattern Is Regulated by ERG Voltage-Gated K+ Channels

Locus coeruleus (LC) neurons, with their extensive innervations throughout the brain, control a broad range of physiological processes. Several ion channels have been characterized in LC neurons that control intrinsic membrane properties and excitability. However, ERG (ether-à-go-go-related gene) K+ channels that are particularly important in setting neuronal firing rhythms and automaticity have not as yet been discovered in the LC. Moreover, the neurophysiological and pathophysiological roles of ERG channels in the brain remain unclear despite their expression in several structures. By performing immunohistochemical investigations, we found that ERG-1A, ERG-1B, ERG-2 and ERG-3 are highly expressed in the LC neurons of mice. To examine the functional role of ERG channels, current-clamp recordings were performed on mouse LC neurons in brain slices under visual control. ERG channel blockade by WAY-123,398, a class III anti-arrhythmic agent, increased the spontaneous firing activity and discharge irregularity of LC neurons. Here, we have shown the presence of distinct ERG channel subunits in the LC which play an imperative role in modulating neuronal discharge patterns. Thus, we propose that ERG channels are important players behind the changes in, and/or maintenance of, LC firing patterns that are implicated in the generation of different behaviors and in several disorders.

Interactive effects of apneic and baroreflex stress on neuronal coding strategies in human muscle sympathetic nerve activity

The sympathetic nervous system exhibits patterns of action potential (AP) discharge in human muscle sympathetic nerve activity that suggest coding strategies express reflex specificity. This study explored the interactive effects of baroreceptor unloading using lower body negative pressure (LBNP) and volitional end-expiratory apnea (APN) on sympathetic postganglionic neuronal discharge patterns inferred from the firing patterns of differently sized sympathetic AP clusters. Seven individuals were studied using multiunit microneurography (fibular) and a continuous wavelet approach to quantify AP discharge probability, recruitment, and latency during APN performed under ambient conditions, -10, and -40 mmHg LBNP. Compared with the ambient condition, LBNP increased AP discharge rate at -10 and -40 mmHg and recruited larger previously silent sympathetic neurons at -40 mmHg. Compared with spontaneous breathing, APN increased AP discharge when performed during the ambient condition (Δ351 ± 132 AP/min), -10 mmHg (Δ423 ± 184 AP/min), and -40 mmHg (Δ355 ± 278 AP/min; main effect APN: P < 0.01; LBNP-by-APN interaction: P = 0.55). APN recruited larger previously silent AP clusters during the ambient condition (Δ4 ± 3; P < 0.02) and -10 mmHg (Δ4 ± 3; P < 0.01), but not -40 mmHg (Δ0 ± 2; P = 0.53; LBNP-by-APN: P < 0.01). LBNP did not affect AP latency. However, APN reduced AP latency similarly during all conditions (ambient pressure: Δ-0.04 ± 0.04s, -10 mmHg: Δ-0.03 ± 0.03s, -40 mmHg: Δ-0.03 ± 0.04s; main effect APN: P < 0.01; LBNP-by-APN: P = 0.48). These data indicate that apneic and baroreflex mechanisms appear to additively modify the axonal discharge rate of previously active sympathetic postganglionic neurons and interact to affect recruitment of previously silent sympathetic neurons. Reductions in AP latency due to apneic stress were not impacted by baroreflex unloading.NEW & NOTEWORTHY Discrete physiological stressors differentially affect sympathetic postganglionic neuronal rate-, population-, and temporal-coding strategies. When performing end-expiratory apnea (APN) during graded baroreflex unloading via lower body negative pressure (LBNP), we found: 1) augmented sympathetic axonal firing probability, 2) recruitment of larger and previously silent sympathetic postganglionic neurons at ambient and -10 mmHg, but not -40 mmHg LBNP, and 3) APN reduced axonal discharge latency similarly across all conditions, independent of the level of baroreflex unloading.

A New Spike Sorting Algorithm Based on Continuous Wavelet Transform and Investigating Its Effect on Improving Neural Decoding Accuracy

Spike sorting is an essential step in extracting neuronal discharge patterns which help to decode different activities in the neural system. Therefore, improving the spike sorting accuracy can improve neural decoding performance subsequently. Although many methods are suggested for spike sorting, few studies have evaluated their effect on neural decoding performance. In this paper, a method of spike sorting based on an optimized selection of the parameters in the continuous wavelet transform (CWT) is proposed. The proposed algorithm was tested on a simulated dataset and two publicly available benchmark datasets to evaluate its performance in spike sorting. To evaluate the effect of utilizing different spike sorting algorithms on neural decoding performance, real data was used in which the aim was to decode the force applied by the rat's hand to a pedal continuously from the intra-cortical data of the primary motor area of the cortex. The extracted neuronal firing rates by the spike sorting algorithms were applied to a partial least squares regression to decode the force signal. In the simulation study, the proposed spike sorting algorithm based on optimized wavelet parameter selection outperformed both the WaveClus spike sorting and traditional PCA-based spike sorting algorithms. The results showed the superiority of the spike sorting algorithm based on optimal wavelet parameters compared to classical discrete wavelet transform (DWT) or PCA-based spike sorting methods in decoding real intracortical data. Overall, the results indicate that it is possible to improve neural decoding performance by improving the spike sorting accuracy.

On the Origin of Paroxysmal Depolarization Shifts: The Contribution of Cav1.x Channels as the Common Denominator of a Polymorphous Neuronal Discharge Pattern

Since their discovery in the 1960s, the term paroxysmal depolarization shift (PDS) has been applied to a wide variety of reinforced neuronal discharge patterns. Occurrence of PDS as cellular correlates of electrographic spikes during latent phases of insult-induced rodent epilepsy models and their resemblance to giant depolarizing potentials (GDPs) nourished the idea that PDS may be involved in epileptogenesis. Both GDPs and – in analogy – PDS may lead to progressive changes of neuronal properties by generation of pulsatile intracellular Ca2+ elevations. Herein, a key element is the gating of L-type voltage gated Ca2+ channels (LTCCs, Cav1.x family), which may convey Ca2+ signals to the nucleus. Accordingly, the present study investigates various insult-associated neuronal challenges for their propensities to trigger PDS in a LTCC-dependent manner. Our data demonstrate that diverse disturbances of neuronal function are variably suited to induce PDS-like events, and the contribution of LTCCs is essential to evoke PDS in rat hippocampal neurons that closely resemble GDPs. These PDS appear to be initiated in the dendritic sub-compartment. Their morphology critically depends on the position of recording electrodes and on their rate of occurrence. These results provide novel insight into induction mechanisms, origin, variability, and co-existence of PDS with other discharge patterns and thereby pave the way for future investigations regarding the role of PDS in epileptogenesis.

The hidden, period-adding, mixed-mode oscillations and control in a HR neuron under electromagnetic induction

Abstract Researching the discharge patterns of neurons under electromagnetic induction is of great practical significance for understanding the complex nervous system. In this paper, the discharge patterns of a HR neuron under electromagnetic induction(here called magnetic flux HR neuron system), including hidden, period-adding, mixed-mode oscillations and their control are researched by combining theoretical analysis and numerical simulations. Firstly, the distribution and stability of the equilibrium point in the magnetic flux HR neuron system is theoretical analyzed based on the Matcont software, and it is found that there are one supercritical and two subcritical Hopf bifurcation points. Through further analysis, the hidden limit cycle attractor and its existence range are shown near the subcritical Hopf bifurcation points. Then, the complex period-adding, mixed-mode and coexistence oscillations are simulated and analyzed in the two-parameter space. In the following, the stability control of subcritical Hopf bifurcation is realized by using the Washout controller, and the undesirable hidden discharge behavior is eliminated. At last, the Hamilton energy feedback controller is designed to control the mixed-mode oscillation of the membrane voltage to desired discharge states effectively, and the energy transform can also be detected in the control process. The results provide useful research for understanding the discharge pattern of the magnetic flux HR neuron and controlling membrane voltage transfer.

What is the true discharge rate and pattern of the striatal projection neurons in Parkinson's disease and Dystonia?

Dopamine and striatal dysfunctions play a key role in the pathophysiology of Parkinson's disease (PD) and Dystonia, but our understanding of the changes in the discharge rate and pattern of striatal projection neurons (SPNs) remains limited. Here, we recorded and examined multi-unit signals from the striatum of PD and dystonic patients undergoing deep brain stimulation surgeries. Contrary to earlier human findings, we found no drastic changes in the spontaneous discharge of the well-isolated and stationary SPNs of the PD patients compared to the dystonic patients or to the normal levels of striatal activity reported in healthy animals. Moreover, cluster analysis using SPN discharge properties did not characterize two well-separated SPN subpopulations, indicating no SPN subpopulation-specific (D1 or D2 SPNs) discharge alterations in the pathological state. Our results imply that small to moderate changes in spontaneous SPN discharge related to PD and Dystonia are likely amplified by basal ganglia downstream structures.

Non-invasive analysis of motor neurons controlling the intrinsic and extrinsic muscles of the hand

Objective. We present a non-invasive framework for investigating efferent commands to 14 extrinsic and intrinsic hand muscles. We extend previous studies (limited to a few muscles) on common synaptic input among pools of motor neurons in a large number of muscles. Approach. Seven subjects performed sinusoidal isometric contractions to complete seven types of grasps, with each finger and with three combinations of fingers in opposition with the thumb. High-density surface EMG (HD-sEMG) signals (384 channels in total) recorded from the 14 muscles were decomposed into the constituent motor unit action potentials. This provided a non-invasive framework for the investigation of motor neuron discharge patterns, muscle coordination and efferent commands of the hand muscles during grasping. Moreover, during grasping tasks, it was possible to identify common neural information among pools of motor neurons innervating the investigated muscles. For this purpose, principal component analysis (PCA) was applied to the smoothed discharge rates of the decoded motor units. Main results. We found that the first principal component (PC1) of the ensemble of decoded motor neuron spike trains explained a variance of (53.0 ± 10.9) % and was positively correlated with force (R = 0.67 ± 0.10 across all subjects and tasks). By grouping the pools of motor neurons from extrinsic or intrinsic muscles, the PC1 explained a proportion of variance of (57.1 ± 11.3) % and (56.9 ± 11.8) %, respectively, and was correlated with force with R = 0.63 ± 0.13 and 0.63 ± 0.13, respectively. Significance. These observations demonstrate a low dimensional control of motor neurons across multiple muscles that can be exploited for extracting control signals in neural interfacing. The proposed framework was designed for hand rehabilitation perspectives, such as post-stroke rehabilitation and hand-exoskeleton control.

Adrenergic activation of cardiac preganglionic neurons in the Nucleus Ambiguus

Cholinergic neurons within the nucleus ambiguus (NAm) are the major parasympathetic preganglionic neurons innervating heart. This study characterized the excitability of NAm neurons using in vitro acute brainstem slice preparations obtained from young adult mice. Cholinergic premotor NA neurons were identified based on their expression of tdTomato fluorescence in the Chat‐Cre:floxed‐tdTomato mouse line. Retrograde labeling of pericardiac axon terminals study confirmed cholinergic NAm neurons with large soma as preganglionic cells. In current‐clamp recordings, a brief hyperpolarizing current evoked rebound action potentials (APs). Low voltage‐activated, T‐type calcium current (ICaT) is required for this rebound discharge pattern of NAm neurons. Voltage‐clamp recordings detected a significant T‐current in NA neurons, and quantitative in situ hybridization analysis identified Cav3.1 and 3.2 channels as the major contributors. These preganglionic neurons are strongly activated by adrenergic agonists in vitro. Bath application of adrenergic agonists, epinephrine (10 μM) and norepinephrine (20 μM), induced spontaneous action potentials in these neurons. Inhibition of synaptic ionotropic receptors did not prevent the adrenergic activation, suggesting a minor contribution of synaptic mechanism. Instead, adrenergic stimulation significantly increased the intrinsic excitability of NA neurons; input resistance of NA neurons was significantly increased and single evoked rebound discharges (normally composed of 1–2 APs) converted to regenerative oscillations with burst of &gt;10APs lasting up to a few seconds. Pharmacological tests suggest that persistent sodium current is an important contributor to the activated action potential generation. Together this study identified basic intrinsic membrane excitability mechanism of NAm and its activation by adrenergic agonists.Support or Funding InformationU01 NS090340 (JLN) AHA Career development award (IA)

Pontine Parabrachial Nucleus (PBN) Neuron Subtypes Involved With the Control of Breathing Frequency

A subregion within the medial PBN plays a key role in the control of expiratory duration (TE) and breathing frequency (fB) 1. Drug‐induced increases in neuronal activity decrease TE, while depression of these neurons increases TE. Activity from these neurons is relayed with short latencies to neurons in the preBötzinger/Bötzinger region 2. This study analyzed the relationship between charateristics of the discharge frequency (Fn) patterns of I, E, phase spanning and non‐respiratory modulated (NRM) PBN neurons and changes in fB induced by local application of neural transmitter agonist and antagonist. Multichannel neuronal recording with highly localized microinjections into the PBN were performed in decerebrate, vagotomized dogs during isocapnic hyperoxia. The phrenic neurogram was used to assess fB responses and identify neuronal discharge patterns. Plots of fB vs. neuronal Fn during induced fB responses produced by microinjections of AMPA and the GABA‐A receptor antagonist bicuculline (BIC) were linear with high correlation values (r &gt; 0.75). Furthermore, it appears that neurons with little or no respiratory modulation appear to be more highly correlated with fB than neurons with strong phasic patterns, suggesting that these neurons may be responsible for the pontine control of fB.Support or Funding InformationSupported by Department of Veterans Affairs grant 2 I01BX000721‐08 (Zuperku) &amp; R01GM112960‐01A1 (Stucke)Example of breathing frequency response (BPM) to microinjected AMPA (green) in PBN and corresponding neuronal responses (red) for 2 neurons (panel A and panel B). Lower: Plots of BPM vs discharge frequency (Fn = Fmax) for two simultaneously recorded neurons, phasic‐I (A) and NRM (B) with corresponding slope and r‐squared values. Top: Cycle‐Triggered Histograms (CTHs)Figure 1

Activation of Preoptic GABAergic or Glutamatergic Neurons Modulates Sleep-Wake Architecture, but Not Anesthetic State Transitions.

The precise mechanism of general anesthesia remains unclear. In the last two decades, there has been considerable focus on the hypothesis that anesthetics co-opt the neural mechanisms regulating sleep. This hypothesis is supported by ample correlative evidence at the level of sleep-promoting nuclei, but causal investigations of potent inhaled anesthetics have not been conducted. Here, we tested the hypothesis that chemogenetic activation of discrete neuronal subpopulations within the median preoptic nucleus (MnPO) and ventrolateral preoptic nucleus (VLPO) of the hypothalamus would modulate sleep/wake states and alter the time to loss and resumption of consciousness associated with isoflurane, a potent halogenated ether in common clinical use. We show that activating MnPO/VLPO GABAergic or glutamatergic neurons does not alter anesthetic induction or recovery time. However, activation of these neuronal subpopulations did alter sleep-wake architecture. Notably, we report the novel finding that stimulation of VLPO glutamatergic neurons causes a strong increase in wakefulness. We conclude that activation of preoptic GABAergic or glutamatergic neurons that increase sleep or wakefulness does not substantively influence anesthetic state transitions. These data indicate that the correlative evidence for a mechanistic overlap of sleep and anesthesia at the level of an individual nucleus might not necessarily have strong causal significance.

Conditioning by subthreshold synaptic input changes the intrinsic firing pattern of CA3 hippocampal neurons.

Unlike synaptic strength, intrinsic excitability is assumed to be a stable property of neurons. For example, learning of somatic conductances is generally not incorporated into computational models, and the discharge pattern of neurons in response to test stimuli is frequently used as a basis for phenotypic classification. However, it is increasingly evident that signal processing properties of neurons are more generally plastic on the timescale of minutes. Here we demonstrate that the intrinsic firing patterns of CA3 neurons of the rat hippocampus in vitro undergo rapid long-term plasticity in response to a few minutes of only subthreshold synaptic conditioning. This plasticity on the spike timing could also be induced by intrasomatic injection of subthreshold depolarizing pulses and was blocked by kinase inhibitors, indicating that discharge dynamics are modulated locally. Cluster analysis of firing patterns before and after conditioning revealed systematic transitions toward adapting and intrinsic burst behaviors, irrespective of the patterns initially exhibited by the cells. We used a conductance-based model to decide appropriate pharmacological blockade and found that the observed transitions are likely due to recruitment of low-voltage calcium and Kv7 potassium conductances. We conclude that CA3 neurons adapt their conductance profile to the subthreshold activity of their input, so that their intrinsic firing pattern is not a static signature, but rather a reflection of their history of subthreshold activity. In this way, recurrent output from CA3 neurons may collectively shape the temporal dynamics of their embedding circuits.NEW & NOTEWORTHY Although firing patterns are widely conserved across the animal phyla, it is still a mystery why nerve cells present such diversity of discharge dynamics upon somatic step currents. Adding a new timing dimension to the intrinsic plasticity literature, here we show that CA3 neurons rapidly adapt through the space of known firing patterns in response to the subthreshold signals that they receive from their embedding circuit, potentially adjusting their network processing to the temporal statistics of their circuit.

Electrical Mode Transition of Hybrid Neuronal Model Induced by External Stimulus and Electromagnetic Induction

Based on a hybrid neuronal model of the Hindmarsh–Rose (HR) model (the slow negative feedback dynamics) with the Wilson model (the fast variable dynamics), the discharge modes of neurons are studied by using bifurcation analysis. When the hybrid neuronal model is driven by external stimulus current, the hybrid neuronal model is capable of simulating an extensive range of bursting patterns with different systemic parameters. With the increase of external stimulus, the multiple discharge patterns of neurons arise, and the electrical modes of the neurons appear for successive transitions. When the hybrid neuronal model is driven by electromagnetic induction, the electrical activities of the neurons have different responses to the variations in the amplitude and the angular frequency of high and low frequency electromagnetic radiations. It is found that the neuronal discharge activity is transformed from chaotic state to periodic state by increasing the angular frequency, and the firing pattern of neuron can be shifted from the bursting state to chaotic state by increasing the amplitude of the low frequency signal.

A Rhesus Monkey With a Naturally Occurring Impairment of Disparity Vergence. II. Abnormal Near Response Cell Activity in the Supraoculomotor Area.

PurposeConvergence insufficiency is a very common disorder that can have significant adverse effects on school performance. When reading, children with this disorder often experience diplopia and headaches. We have recently obtained a rhesus monkey with a naturally occurring impairment of vergence eye movements. In the companion paper, we report behavioral testing that shows a pattern of impairments similar to what clinicians observe in human children with convergence insufficiency, including a receded near point, an exophoria that increases as target distance decreases, and difficulty maintaining an appropriate vergence angle when presented with a large field stimulus at near. For the present case report, we wondered whether these behavioral deficits would be associated with abnormal discharge patterns in brainstem neurons related to vergence eye movements.MethodsSingle unit activity was recorded from near and far response cells in the supraoculomotor area in the vergence-impaired monkey, while he performed a smooth vergence tracking task or fixated visual targets at different distances.ResultsWe found an abnormally weak sensitivity to both vergence angle and vergence velocity. Nonetheless, these neurons modulated in association with contextually inappropriate slow vergence movements that occurred in the absence of saccades but not for slow divergence drifts that immediately followed converging saccades. Modulation of activity was more robust when additional depth cues were available.ConclusionsThese data suggest that disorders affecting vergence eye movements may be associated with impoverished sensory input to the near and far response cells and, perhaps, aberrant tuning in vergence-related neurons.

Cluster Analysis of Neuronal Discharge Patterns During Breathing and the Laryngeal Adductor Reflex with Computer Simulations and Dynamic Visualizations

The laryngeal adductor reflex (LAR) is a simple airway protective behavior that closes the vocal folds in response to mechanical or chemical stimulation of sensory afferents in the larynx. Previous work suggested that the intra‐medullary pathway that is responsible for activating laryngeal motoneurons is composed of as little as two synapses. We speculated that the central pathways supporting this behavior are more complex and involve neurons of several different phenotypes. Breathing and non‐breathing modulated neurons (n=632) were recorded with multiple electrode arrays in the ventral respiratory column (ventral respiratory group, pre‐Bötzinger, Bötzinger), pons, raphé, dorsal lateral medulla and spinal cord of decerebrate, paralyzed, vagus‐intact cats (n=13). The LAR was induced by electrical stimulation of the superior laryngeal nerve. We classified brainstem neuron activity phenotypes using a quantitative, reproducible clustering routine during baseline breathing and the LAR. We identified 25 breathing phenotypes that were mapped onto 16 LAR phenotypes. These results were used to produce a simplified model and simulations of the LAR. A 3‐D brainstem atlas displayed neuronal firing rates during periods of baseline breathing and/or the LAR, illuminated in proportion to firing rate. These data support distinct rather than a continuum of phenotypes based on discharge patterns during breathing as well as during the LAR.Support or Funding InformationSupport: OT2OD023854‐01, HL109025, HL131716This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.