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1. Systematic generation of biophysically detailed models with generalization capability for non-spiking neurons

   https://doi.org/10.1371/journal.pone.0268380  

   Naudin, Loïs ; Jiménez Laredo, Juan Luis ; Liu, Qiang ; Corson, Nathalie ( May 2022 , PLOS ONE)

   Guo, Daqing (Ed.)

   Unlike spiking neurons which compress continuous inputs into digital signals for transmitting information via action potentials, non-spiking neurons modulate analog signals through graded potential responses. Such neurons have been found in a large variety of nervous tissues in both vertebrate and invertebrate species, and have been proven to play a central role in neuronal information processing. If general and vast efforts have been made for many years to model spiking neurons using conductance-based models (CBMs), very few methods have been developed for non-spiking neurons. When a CBM is built to characterize the neuron behavior, it should be endowed with generalization capabilities ( i.e . the ability to predict acceptable neuronal responses to different novel stimuli not used during the model’s building). Yet, since CBMs contain a large number of parameters, they may typically suffer from a lack of such a capability. In this paper, we propose a new systematic approach based on multi-objective optimization which builds general non-spiking models with generalization capabilities. The proposed approach only requires macroscopic experimental data from which all the model parameters are simultaneously determined without compromise. Such an approach is applied on three non-spiking neurons of the nematode Caenorhabditis elegans ( C. elegans ), amore »well-known model organism in neuroscience that predominantly transmits information through non-spiking signals. These three neurons, arbitrarily labeled by convention as RIM, AIY and AFD, represent, to date, the three possible forms of non-spiking neuronal responses of C. elegans .« less
2. Multiscale low-dimensional motor cortical state dynamics predict naturalistic reach-and-grasp behavior

   https://doi.org/10.1038/s41467-020-20197-x  

   Abbaspourazad, Hamidreza ; Choudhury, Mahdi ; Wong, Yan T. ; Pesaran, Bijan ; Shanechi, Maryam M. ( January 2021 , Nature Communications)

   Motor function depends on neural dynamics spanning multiple spatiotemporal scales of population activity, from spiking of neurons to larger-scale local field potentials (LFP). How multiple scales of low-dimensional population dynamics are related in control of movements remains unknown. Multiscale neural dynamics are especially important to study in naturalistic reach-and-grasp movements, which are relatively under-explored. We learn novel multiscale dynamical models for spike-LFP network activity in monkeys performing naturalistic reach-and-grasps. We show low-dimensional dynamics of spiking and LFP activity exhibited several principal modes, each with a unique decay-frequency characteristic. One principal mode dominantly predicted movements. Despite distinct principal modes existing at the two scales, this predictive mode was multiscale and shared between scales, and was shared across sessions and monkeys, yet did not simply replicate behavioral modes. Further, this multiscale mode’s decay-frequency explained behavior. We propose that multiscale, low-dimensional motor cortical state dynamics reflect the neural control of naturalistic reach-and-grasp behaviors.
3. GHz Ultrasonic Chip-Scale Device Induces Ion Channel Stimulation in Human Neural Cells

   https://doi.org/10.1038/s41598-020-58133-0  

   Balasubramanian, Priya S. ; Singh, Ankur ; Xu, Chris ; Lal, Amit ( February 2020 , Scientific Reports)

   Emergent trends in the device development for neural prosthetics have focused on establishing stimulus localization, improving longevity through immune compatibility, reducing energy re-quirements, and embedding active control in the devices. Ultrasound stimulation can single-handedly address several of these challenges. Ultrasonic stimulus of neurons has been studied extensively from 100 kHz to 10 MHz, with high penetration but less localization. In this paper, a chip-scale device consisting of piezoelectric Aluminum Nitride ultrasonic transducers was engineered to deliver gigahertz (GHz) ultrasonic stimulus to the human neural cells. These devices provide a path towards complementary metal oxide semiconductor (CMOS) integration towards fully controllable neural devices. At GHz frequencies, ultrasonic wavelengths in water are a few microns and have an absorption depth of 10–20 µm. This confinement of energy can be used to control stimulation volume within a single neuron. This paper is the first proof-of-concept study to demonstrate that GHz ultrasound can stimulate neuronsin vitro. By utilizing optical calcium imaging, which records calcium ion flux indicating occurrence of an action potential, this paper demonstrates that an application of a nontoxic dosage of GHz ultrasonic waves$$(\ge 0.05\frac{W}{c{m}^{2}})$$$\left(\ge 0.05\frac{W}{c{m}^2}\right)$caused an average normalized fluorescence intensity recordings >1.40 for the calcium transients. Electrical effects due to chip-scale ultrasound delivery wasmore »discounted as the sole mechanism in stimulation, with effects tested atα = 0.01 statistical significance amongst all intensities and con-trol groups. Ionic transients recorded optically were confirmed to be mediated by ion channels and experimental data suggests an insignificant thermal contributions to stimulation, with a predicted increase of 0.03^oCfor$$1.2\frac{W}{c{m}^{2}}\cdot $$$1.2\frac{W}{c{m}^2}\cdot$This paper paves the experimental framework to further explore chip-scale axon and neuron specific neural stimulation, with future applications in neural prosthetics, chip scale neural engineering, and extensions to different tissue and cell types.

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4. Mathematical Modeling and Analyses of Interspike-Intervals of Spontaneous Activity in Afferent Neurons of the Zebrafish Lateral Line

   https://doi.org/10.1038/s41598-018-33064-z  

   Song, Sangmin ; Lee, Ji Ah ; Kiselev, Ilya ; Iyengar, Varun ; Trapani, Josef G. ; Tania, Nessy ( October 2018 , Scientific Reports)

   Without stimuli, hair cells spontaneously release neurotransmitter leading to spontaneous generation of action potentials (spikes) in innervating afferent neurons. We analyzed spontaneous spike patterns recorded from the lateral line of zebrafish and found that distributions of interspike intervals (ISIs) either have an exponential shape or an “L” shape that is characterized by a sharp decay but wide tail. ISI data were fitted to renewal-process models that accounted for the neuron refractory periods and hair-cell synaptic release. Modeling the timing of synaptic release using a mixture of two exponential distributions yielded the best fit for our ISI data. Additionally, lateral line ISIs displayed positive serial correlation and appeared to exhibit switching between faster and slower modes of spike generation. This pattern contrasts with previous findings from the auditory system where ISIs tended to have negative serial correlation due to synaptic depletion. We propose that afferent neuron innervation with multiple and heterogenous hair-cells synapses, each influenced by changes in calcium domains, can serve as a mechanism for the random switching behavior. Overall, our analyses provide evidence of how physiological similarities and differences between synapses and innervation patterns in the auditory, vestibular, and lateral line systems can lead to variations in spontaneousmore »activity.

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5. Resurgent Na+ currents promote ultrafast spiking in projection neurons that drive fine motor control

   https://doi.org/10.1038/s41467-021-26521-3  

   Zemel, Benjamin M. ; Nevue, Alexander A. ; Dagostin, Andre ; Lovell, Peter V. ; Mello, Claudio V. ; von Gersdorff, Henrique ( November 2021 , Nature Communications)

   The underlying mechanisms that promote precise spiking in upper motor neurons controlling fine motor skills are not well understood. Here we report that projection neurons in the adult zebra finch song nucleus RA display robust high-frequency firing, ultra-narrow spike waveforms, superfast Na⁺current inactivation kinetics, and large resurgent Na⁺currents (I_NaR). These properties of songbird pallial motor neurons closely resemble those of specialized large pyramidal neurons in mammalian primary motor cortex. They emerge during the early phases of song development in males, but not females, coinciding with a complete switch of Na+ channel subunit expression from Navβ3 to Navβ4. Dynamic clamping and dialysis of Navβ4’s C-terminal peptide into juvenile RA neurons provide evidence that Navβ4, and its associated I_NaR, promote neuronal excitability. We thus propose that I_NaRmodulates the excitability of upper motor neurons that are required for the execution of fine motor skills.