Biology subjects

Mirzakhalili, E.

Publications and source records attributed to Mirzakhalili, E..

4 recordsLinked to original sources

bioRxiv2024

Disrupted Hippocampal Theta-Gamma Coupling and Spike-Field Coherence Following Experimental Traumatic Brain Injury

Traumatic brain injury (TBI) often results in persistent learning and memory deficits, likely due to disrupted hippocampal circuitry underlying these processes. Precise temporal control of hippocampal neuronal activity is thought to be important for memory encoding and retrieval and is supported by oscillations that dynamically organize single unit firing. Using high-density laminar electrophysiology, we found a loss of oscillatory power across CA1 lamina, with a profound, layer-specific reduction in theta-gamma phase amplitude coupling in injured rats. Interneurons from injured animals were less strongly entrained to theta and gamma oscillations, but both interneurons and pyramidal cells from injured animals became more strongly entrained to theta during periods of high theta power. During quiet immobility, sharp-wave ripple amplitudes were lower in injured animals compared to shams. These results reveal physiological deficits across brain states that may contribute to TBI-associated learning and memory impairments and elucidate potential targets for future neuromodulation therapies.

neuroscience↗

bioRxiv2024

High-frequency amplitude-modulated sinusoidal stimulation induces desynchronized yet controllable neural firing

Regaining sensory feedback is critical for people living with limb amputation. Electrical stimulation of sensory fibers in peripheral nerves has been shown to restore focal percepts in the missing limb. However, conventional rectangular current pulses induce sensations often described as unnatural, likely due to the synchronous and periodic nature of activity they evoke. Here we introduce a fast-oscillating amplitude-modulated sinusoidal (FAMS) stimulation waveform that desynchronizes neural activity. Using computational modeling, we show that sinusoidal waveforms evoke asynchronous and irregular firing patterns, with frequency-dependent effects. Leveraging both low- and high-frequency mechanisms, FAMS exploits membrane nonlinearities to enhance neuron-specific differences. In a feline model of peripheral nerve stimulation, FAMS evoked activity that was more asynchronous than conventional rectangular pulses, while remaining easily controllable with simple stimulation parameters. Importantly, in human experiments using noninvasive stimulation of the median nerve, participants reported that FAMS evoked more natural sensations compared to rectangular biphasic pulses in a two-alternative forced-choice task. The preference for FAMS increased at higher intensities above sensory threshold, despite intensity-matched stimulation across waveform types. These findings provide evidence that reduced synchrony in afferent recruitment translates into more naturalistic and comfortable sensory percepts. Together, our results establish FAMS as a promising biomimetic stimulation strategy with potential for clinical applications in sensory feedback restoration. One Sentence SummaryA new electrical stimulation waveform allows for evoking and controlling more naturalistic neural activity than can be achieved with traditional stimulation waveforms.

bioengineering↗

bioRxiv2018

Caenorhabditis elegans locomotion dynamics is affected by internally localized magnetic fields

C. elegans nematodes are a model organism used broadly to investigate the impact of environmental factors on physiology and behavior. Here, C. elegans with internalized paramagnetic nanoparticles were placed inside magnetic field to explore effects on locomotion. We hypothesize that internalized paramagnetic nanoparticles combined with external magnetic field affect C. elegans locomotion machinery. To test our hypothesis, we used young adult C. elegans fed on bacteria mixed with paramagnetic nanoparticles of 1 m, 100 nm and 40 nm diameter. The presence of nanoparticles inside the worms body (alimentary canal, body muscle) was verified by fluorescent and electron microscopy. A custom-made software was used to track freely moving C. elegans in the absence or presence of magnetic field sequentially for 200+200 sec. We used established metrics to quantify locomotion-related parameters, including posture, motion and path features. Key features of C. elegans locomotion (increased body bends and stay ratio, decreased range, forward movement, and speed along the magnetic field) were affected in worms with internalized nanoparticles of 100 nm and 1 m in the presence of magnetic field, in contrast to untreated worms. Our work contributes on clarifying the effect of internalized paramagnetic nanoparticles, combined with magnetic field, on C. elegans locomotion. Summary StatementC. elegans with internalized paramagnetic nanoparticles are placed inside magnetic field to explore effects on locomotion. Results support the potential of C. elegans to investigate the impact of the above environmental factors on behavior.

biophysics↗

bioRxiv2017

A mathematical and computational model of the calcium dynamics in Caenorhabditis elegans ASH sensory neuron

We propose a mathematical and computational model that captures the stimulus-generated Ca2+ transients in the C. elegans ASH sensory neuron. The model is built based on biophysical events and molecular cascades known to unfold as part of neurons Ca2+ homeostasis mechanism, as well as on Ca2+ signaling events. The state of ion channels is described by their probability of being activated or inactivated, and the remaining molecular states are based on biochemically defined kinetic equations with phenomenological adjustments. We estimate the parameters of the model using experimental data of hyperosmotic stimulus-evoked Ca2+ transients detected with a FRET sensor in young and aged worms, unstressed and exposed to oxidative stress. We use a hybrid optimization method composed of a multi-objective genetic algorithm and nonlinear least-squares to estimate the model parameters. We first obtain the model parameters for young unstressed worms. Next, we use these values of the parameters as a starting point to identify the model parameters for stressed and aged worms. We show that the model, in combination with experimental data, corroborates literature results. In addition, we demonstrate that our model can be used to predict ASH response to complex combinations of stimulation pulses. The proposed model includes for the first time the ASH Ca2+ dynamics observed during both \"on\" and \"off\" responses. This mathematical and computational effort is the first to propose a dynamic model of the Ca2+ transients mechanism in C. elegans neurons, based on biochemical pathways of the cells Ca2+ homeostasis machinery.\n\nSignificance StatementC. elegans is widely used as a model system for monitoring neuronal Ca2+ transients. The ASH neuron is the subject of several such studies, primarily due to its key importance as a polymodal nociceptor. However, despite its pivotal role in C. elegans biology, and the special characteristics of its stimulus-evoked Ca2+ transients (e.g., the \"off\" response), no mathematical or computational model has been developed to include special features of ASH Ca2+ dynamics, i.e. the \"off\" response. The model includes for the first time the ASH Ca2+ dynamics observed during both \"on\" and \"off\" responses, and is the first to propose a dynamical model of the C. elegans Ca2+ transients mechanism based on biochemical pathways of the cells Ca2+ homeostasis machinery.\n\nAbbreviations

neuroscience↗