Netoff, T. I. | bioRxiv Science

bioRxiv2021

Strength-frequency curve for micromagnetic neurostimulation through EPSPs on rat hippocampal neurons and numerical modeling of magnetic microcoil (μcoil)

ObjectiveThe objective of this study was to measure the effect of micromagnetic stimulation (MS) on hippocampal neurons, by using single microcoil (coil) prototype, Magnetic Pen (MagPen). MagPen will be used to stimulate the CA3 region magnetically and excitatory post synaptic potential (EPSP) response measurements will be made from the CA1 region. The threshold for micromagnetic neurostimulation as a function of stimulation frequency of the current driving the coil will be demonstrated. Finally, the optimal stimulation frequency of the current driving the coil to minimize power will be estimated. ApproachA biocompatible, watertight, non-corrosive prototype, MagPen was built, and customized such that it is easy to adjust the orientation of the coil and its distance over the hippocampal tissue in an in vitro recording setting. Finite element modeling (FEM) of the coil design was performed to estimate the spatial profiles of the magnetic flux density (in T) and the induced electric fields (in V/m). The induced electric field profiles generated at different values of current applied to the coil can elicit a neuron response, which was validated by numerical modeling. The modeling settings for the coil were replicated in experiments on rat hippocampal neurons. Main resultsThe preferred orientation of MagPen over the Schaffer Collateral fibers was demonstrated such that they elicit a neuron response. The recorded EPSPs from CA1 region due to MS at CA3 region were validated by applying tetrodotoxin (TTX). Application of TTX to the hippocampal slice blocked the EPSPs from MS while after prolonged TTX washout, a partial recovery of the EPSP from MS was observed. Finally, it was interpreted through numerical analysis that increasing frequency of the current driving the coil, led to a decrease in the current amplitude threshold for micromagnetic neurostimulation. SignificanceThis work reports that micromagnetic neurostimulation can be used to evoke population EPSP responses in the CA1 region of the hippocampus. It demonstrates the strengthfrequency curve for MS and its unique features related to orientation dependence of the coils, spatial selectivity and stimulation threshold related to distance dependence. Finally, the challenges related to MS experiments were studied including ways to overcome them.

bioengineering↗

bioRxiv2021

Realistic alpha oscillations and transient responses in a cortical microcircuit model

Neural-mass modeling of neural population data (EEG, ECoG, or LFPs) has shown promise both in elucidating the neural processes underlying cortical rhythms and changes in brain state, as well as offering a framework for testing the interplay between these rhythms and information processing. Models of cortical alpha rhythms (8 - 12 Hz) and their impact in visual sensory processing have been at the forefront of this effort, with the Jansen-Rit being one of the more popular models in this domain. The Jansen-Rit model, however, fails in reproducing key physiological observations including the level of inputs that cortical neurons receive and their responses to visual transients. To address these issues we generated a neural mass model that complies better with synaptic mediated dynamics, intrinsic alpha behavior, and produces realistic responses. The model is robust to many changes in parameter values but critically depends on the ratio of excitation to inhibition, producing response transients whose features are dependent on this ratio and alpha phase and power. The model is sufficiently flexible so as to be able to easily replicate the range of low frequency oscillations observed in different studies. Consistent with experimental observations, we find phase-dependent response dynamics to both visual and electrical stimulation using this model. The model suggests that stimulation facilitates alpha at particular phases and suppresses it in others due to a phase dependent lag in inhibitory responses. Hence, the model generates insight into the physiological parameters responsible for intrinsic oscillations and testable hypotheses regarding the interactions between visual and electrical stimulation on those oscillations. Author summaryWhile there is increasing evidence of the fundamental role brain states play in shaping information processing in the cerebral cortex, a mechanistic understanding of how those brain states are manifested and alter the signals underlying sensory processing and decision making has proved challenging. To address this issue we have modeled a well established signature of inattention in visual cortex: synchronized low frequency (8 - 12 Hz) oscillations. To allow for inferences regarding the local generation of these rhythms within a cortical microcircuit we used a neural mass model approach that incorporates physiologically realistic interactions between 3 populations of neurons. Our model is able to explain a variety of experimental observations that previous neural mass models have not, including spontaneous rhythms in the absence of input, the faithful transmission of strong input transients, a range of oscillation frequencies, and phase dependent visual responses. The model is robust to a range of parameters, but critically depends on the balance between local excitation and inhibition.

neuroscience↗