The Morris-Lecar neuron model embeds a leaky integrate-and-fire model

We show that the stochastic Morris-Lecar neuron, in a neighborhood of its stable point, can be approximated by a two-dimensional Ornstein-Uhlenbeck (OU) modulation of a constant circular motion. The associated radial OU process is an example of a leaky integrate-and-fire (LIF) model prior to firing. A new model constructed from a radial OU process together with a simple firing mechanism based on detailed Morris-Lecar firing statistics reproduces the Morris-Lecar Interspike Interval (ISI) distribution, and has the computational advantages of a LIF. The result justifies the large amount of attention paid to the LIF models.Comment: 19 pages, 6 figure

Communications Biophysics

Contains research objectives, summary of research and reports on two research projects.National Institutes of Health (Grant 5 PO1 GM-14940-02)Joint Services Electronics Programs (U. S. Army, U.S. Navy, and U. S. Air Force) under Contract DA 28-043-AMC-02536(E)National Aeronautics and Space Administration (Grant NGL 22-009-304)National Institutes of Health (Grant 5 TO1 GM-01555-02)National Institutes of Health (Grant NB-08082-01

Self-Consistent Analyses For Potential Conduction Block in Nerves By An Ultrashort High-Intensity Electric Pulse

Simulation studies are presented that probe the possibility of using high-field (\u3e100kV ∕ cm), short-duration (∼50ns) electrical pulses for nonthermal and reversible cessation of biological electrical signaling pathways. This would have obvious applications in neurophysiology, clinical research, neuromuscular stimulation therapies, and even nonlethal bioweapons development. The concept is based on the creation of a sufficiently high density of pores on the nerve membrane by an electric pulse. This modulates membrane conductance and presents an effective electrical short to an incident voltage wave traveling across a nerve. Net blocking of action potential propagation can then result. A continuum approach based on the Smoluchowski equation is used to treat electroporation. This is self-consistently coupled with a distributed circuit representation of the nerve dynamics. Our results indicate that poration at a single neural segment would be sufficient to produce an observable, yet reversible, effect

An Operating Principle of the Cerebral Cortex, and a Cellular Mechanism for Attentional Trial-and-Error Pattern Learning and Useful Classification Extraction

A feature of the brains of intelligent animals is the ability to learn to respond to an ensemble of active neuronal inputs with a behaviorally appropriate ensemble of active neuronal outputs. Previously, a hypothesis was proposed on how this mechanism is implemented at the cellular level within the neocortical pyramidal neuron: the apical tuft or perisomatic inputs initiate "guess" neuron firings, while the basal dendrites identify input patterns based on excited synaptic clusters, with the cluster excitation strength adjusted based on reward feedback. This simple mechanism allows neurons to learn to classify their inputs in a surprisingly intelligent manner. Here, we revise and extend this hypothesis. We modify synaptic plasticity rules to align with behavioral time scale synaptic plasticity (BTSP) observed in hippocampal area CA1, making the framework more biophysically and behaviorally plausible. The neurons for the guess firings are selected in a voluntary manner via feedback connections to apical tufts in the neocortical layer 1, leading to dendritic Ca2+ spikes with burst firing, which are postulated to be neural correlates of attentional, aware processing. Once learned, the neuronal input classification is executed without voluntary or conscious control, enabling hierarchical incremental learning of classifications that is effective in our inherently classifiable world. In addition to voluntary, we propose that pyramidal neuron burst firing can be involuntary, also initiated via apical tuft inputs, drawing attention towards important cues such as novelty and noxious stimuli. We classify the excitations of neocortical pyramidal neurons into four categories based on their excitation pathway: attentional versus automatic and voluntary/acquired versus involuntary. Additionally, we hypothesize that dendrites within pyramidal neuron minicolumn bundles are coupled via depolarization...Comment: 20 pages, 13 figure

An examination of agonist and antagonist motor unit firing properties

The interactions between opposing muscle (i.e. agonist and antagonist) groups can be extremely complex, task-dependent, and are still poorly understood. To identify possible origins of the coordination between antagonistic muscle groups, the common or shared sources of neural input need to be understood. The assessment and manipulation of motor unit firing properties, such as synchronization, can provide information regarding the common inputs to opposing muscles. PURPOSE: The purpose of this study was to introduce various interventions to systematically manipulate both agonist and antagonist motor unit firing properties, and obtain a better understanding of the interactions between the two. METHODS: Muscle activity was detected from the biceps brachii ("agonist") and the triceps brachii ("antagonist") during isometric forearm flexions. The signals from these muscles were decomposed into individual motor unit action potential trains. Subsequently, various firing properties such as mean firing rate, recruitment threshold, and synchronization were calculated. On two separate visits, either the agonist or antagonist muscle was fatigued. During another two visits, either the agonist or antagonist muscle underwent 18 minutes of prolonged stretching, which has been shown to significantly desensitize proprioceptors. RESULTS: During co-activation, the antagonist demonstrated significant motor unit synchronization, but to a lesser extent when compared to the agonist. The antagonist also exhibited a substantially smaller recruitment threshold range and higher average firing rates. Fatigue of the agonist did not show any changes to antagonist motor unit firing properties, despite a significant increase in co-activation. Fatigue of the antagonists produced effects on the motor unit behavior of the agonist, such as decreased motor unit synchronization. It was suggested that group III and IV muscle afferents originating from the antagonist were responsible for the change to the agonist. The stretching interventions provided some mixed results, often providing non-uniform changes across motor unit types. For example, agonist low-threshold motor unit pairs demonstrated an increase in short-term synchronization after agonist stretching, but the high-threshold motor unit pairs exhibited a decrease in synchronization. Future studies to help answer follow-up questions were suggested

A Study of Myoelectric Signal Processing

This dissertation of various aspects of electromyogram (EMG: muscle electrical activity) signal processing is comprised of two projects in which I was the lead investigator and two team projects in which I participated. The first investigator-led project was a study of reconstructing continuous EMG discharge rates from neural impulses. Related methods for calculating neural firing rates in other contexts were adapted and applied to the intramuscular motor unit action potential train firing rate. Statistical results based on simulation and clinical data suggest that performances of spline-based methods are superior to conventional filter-based methods in the absence of decomposition error, but they unacceptably degrade in the presence of even the smallest decomposition errors present in real EMG data, which is typically around 3-5%. Optimal parameters for each method are found, and with normal decomposition error rates, ranks of these methods with their optimal parameters are given. Overall, Hanning filtering and Berger methods exhibit consistent and significant advantages over other methods. In the second investigator-led project, the technique of signal whitening was applied prior to motion classification of upper limb surface EMG signals previously collected from the forearm muscles of intact and amputee subjects. The motions classified consisted of 11 hand and wrist actions pertaining to prosthesis control. Theoretical models and experimental data showed that whitening increased EMG signal bandwidth by 65-75% and the coefficients of variation of temporal features computed from the EMG were reduced. As a result, a consistent classification accuracy improvement of 3-5% was observed for all subjects at small analysis durations (\u3c 100 ms). In the first team-based project, advanced modeling methods of the constant posture EMG-torque relationship about the elbow were studied: whitened and multi-channel EMG signals, training set duration, regularized model parameter estimation and nonlinear models. Combined, these methods reduced error to less than a quarter of standard techniques. In the second team-based project, a study related biceps-triceps surface EMG to elbow torque at seven joint angles during constant-posture contractions. Models accounting for co-contraction estimated that individual flexion muscle torques were much higher than models that did not account for co-contraction

THE INFLUENCE OF Ca2+ REGULATION IN SYNAPTIC FACILITATION OF MOTOR NERVE TERMINALS IN CRAYFISH AND \u3ci\u3eDROSOPHILA\u3c/i\u3e AS WELL AS IN THE PHYSIOLOGICAL REGULATION OF LARVAL \u3ci\u3eDROSOPHILA\u3c/i\u3e HEART

Intracellular Ca2+ ions are highly regulated in animal cells for them to function normally. Since the tight regulation of [Ca2+]i is so ubiquitous among cells, it is not surprising that altered function in [Ca2+]i regulation is associated with a myriad of disease states in humans. This is particularly evident in pacing myocytes and nerve terminals related to synaptic transmission. A common thread through this dissertation is on the role of three regulators proteins that are common to many cell types. These are the plasmalemmal Na+/Ca2+ exchanger (NCX), the Ca2+-ATPase (PMCA) and the SERCA on the endoplasmic reticulum. In chapter 1 a historical overview is provided on how the understanding in the importance of Ca2+ came about. In Chapter 2, I address indirectly the function of residual [Ca2+]i on the efficacy of synaptic transmission by quantal analysis but also develop novel means of assessing quantal analysis to assign a n and p value to particular synapses. Chapters 3 and 4 address the role of the three Ca2+ regulator proteins in short bursts of synaptic transmission related to short-term facilitation or depression depending on the type of neuromuscular junction (NMJ). Two key model NMJs I used were the crayfish (Chapter 3) and the larval Drosophila (Chapter 4). For comparative purposes in investigating the role of the three proteins in [Ca2+]i regulation, I used the Drosophila larval heart preparation (Chapter 5). Throughout these studies, I used various pharmacological and ionic approaches to compromise the function of these Ca2+ channels. The results were unexpected in some cases due to non-specific effects of the pharmacological agent or ionic manipulations. In addition, a mutational line of Drosophila was used to asses SERCA function, but the results at the NMJ were not as expected. However, results with the mutation on the function of the heart were promising. The significance of these studies stresses that multiple approaches to compromise channels is warranted and the findings should be beneficial for future investigators to advance in mechanistic studies

Neutral coding - A report based on an NRP work session

Neural coding by impulses and trains on single and multiple channels, and representation of information in nonimpulse carrier

Neuromodulation impact on nonlinear firing behavior of a reduced model motoneuron with the active dendrite

Neuromodulatory inputs from brainstem systems modulate the normal function of spinal motoneurons by altering the activation properties of persistent inward currents (PICs) in their dendrites. However, the effect of the PIC on firing outputs also depends on its location in the dendritic tree. To investigate the interaction between PIC neuromodulation and PIC location dependence, we used a two-compartment model that was biologically realistic in that it retains directional and frequency-dependent electrical coupling between the soma and the dendrites, as seen in multi-compartment models based on full anatomical reconstructions of motoneurons. Our two-compartment approach allowed us to systematically vary the coupling parameters between the soma and the dendrite to accurately reproduce the effect of location of the dendritic PIC on the generation of nonlinear (hysteretic) motoneuron firing patterns. Our results show that as a single parameter value for PIC activation was either increased or decreased by 20% from its default value, the solution space of the coupling parameter values for nonlinear firing outputs was drastically reduced by approximately 80%. As a result, the model tended to fire only in a linear mode at the majority of dendritic PIC sites. The same results were obtained when all parameters for the PIC activation simultaneously changed only by approximately ±10%. Our results suggest the democratization effect of neuromodulation: the neuromodulation by the brainstem systems may play a role in switching the motoneurons with PICs at different dendritic locations to a similar mode of firing by reducing the effect of the dendritic location of PICs on the firing behavior

Southwest Research Institute assistance to NASA in biomedical areas of the technology utilization program Final report, 1 Feb. 1969 - 24 Aug. 1970

Research progress in technology transfer by NASA Biomedical Application Tea