scholarly journals Calcium activation of cortical neurons by continuous electrical stimulation: Frequency dependence, temporal fidelity, and activation density

2018 ◽  
Vol 97 (5) ◽  
pp. 620-638 ◽  
Author(s):  
Nicholas J. Michelson ◽  
James R. Eles ◽  
Alberto L. Vazquez ◽  
Kip A. Ludwig ◽  
Takashi D. Y. Kozai
2018 ◽  
Author(s):  
Nicholas J. Michelson ◽  
James R. Eles ◽  
Alberto L. Vazquez ◽  
Kip A Ludwig ◽  
Takashi DY Kozai

AbstractElectrical stimulation of the brain has become a mainstay of fundamental neuroscience research and an increasingly prevalent clinical therapy. Despite decades of use in basic neuroscience research and the growing prevalence of neuromodulation therapies, gaps in knowledge regarding activation or inactivation of neural elements over time have limited its ability to adequately interpret evoked downstream responses or fine-tune stimulation parameters to focus on desired responses. In this work, in vivo two-photon microscopy was used to image neuronal calcium activity in layer 2/3 neurons of somatosensory cortex (S1) in male C57BL/6J-Tg(Thy1-GCaMP6s)GP4.3Dkim/J mice during 30 s of continuous electrical stimulation at varying frequencies. We show frequency-dependent differences in spatial and temporal somatic responses during continuous stimulation. Our results elucidate conflicting results from prior studies reporting either dense spherical activation of somas biased towards those near the electrode, or sparse activation of somas at a distance via axons near the electrode. These findings indicate that the neural element specific temporal response local to the stimulating electrode changes as a function of applied charge density and frequency. These temporal responses need to be considered to properly interpret downstream circuit responses or determining mechanisms of action in basic science experiments or clinical therapeutic applications.Significance StatementMicrostimulation of small populations of neurons has the potential to ameliorate symptoms associated with several neurological disorders. However, the specific mechanisms by which microstimulation elicits therapeutic responses are unclear. This work examines the effects of continuous microstimulation on the local population of neurons surrounding the implanted electrode. Stimulation was found to elicit spatiotemporal neuronal responses in a frequency dependent manner. These findings suggest that stimulation frequency may be an important consideration for applications in research or therapy. Further research aimed at understanding these neuronal activation properties may provide insight into the mechanistic mode of action of continuous microstimulation.


2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Da-an Wang ◽  
Qing-zheng Li ◽  
Dong-ming Jia

The capability of regeneration for skeletal muscle after injury depends on the differentiation and proliferation ability of the resident stem cells called satellite cells. It has been reported that electrical stimulation was widely used in clinical conditions to facilitate muscle regeneration after injury, but the characterization of satellite cell responses to the context of low-frequency electrical stimulation in early-phase muscle strain conditions has not been fully clarified. In this study, we aim to investigate the effects of low-frequency electrical stimulation (frequency: 20 Hz; duration: 30 minutes, twice daily) on satellite cell activities in a rat model for the early phase of muscle strain. Firstly, we adopted our previously developed rat model to mimic the early phase of muscle strain in human. After then, we examined the effects of low-frequency electrical stimulation on histopathological changes of the muscle fiber by hematoxylin and eosin (H&E) staining. Finally, we investigated the effects of low-frequency electrical stimulation on satellite cell proliferation and differentiation by quantification of the expression level of the specific proteins using western blot analyses. The muscle strain in biceps femoris muscles of rats can be induced by high-speed rotation from knee flexion 50° to full knee extension at 960°·s-1 angular velocity during its tetany by activating the sciatic nerve, as evidenced by a widening of the interstitial space between fibers, and more edema or necrosis fibers were detected in the model rats without treatment than in control rats. After treatment with low-frequency electrical stimulation (frequency: 20 Hz; duration: 30 minutes, twice daily), the acute strained biceps femoris muscles of rats showed obvious improvement of histomorphology as indicated by more mature muscle fibers with well-ordered formation with clear boundaries. Consistently, the expression levels of the MyoD and myogenin were marked higher than those in the rats in the animal model group, indicating increased satellite cell proliferating and differentiating activities by low-frequency electrical stimulation. This study shows that low-frequency electrical stimulation provides an effective stimulus to upregulate the protein expression of MyoD/myogenin and accelerate the restoration of structure during the early phase of muscle strain. This may have significance for clinical practice. Optimization of low-frequency electrical stimulation parameters may enhance the therapeutic outcome in patients.


1996 ◽  
Vol 75 (3) ◽  
pp. 1283-1300 ◽  
Author(s):  
C. E. Schreiner ◽  
M. W. Raggio

1. Responses of neurons in primary auditory cortex (AI) of the barbiturate-anesthetized adult cat were studied using cochlear stimulation with electrical and acoustic stimuli. Neuronal responses to acoustic stimulation with brief biphasic clicks of the ear ipsilateral to the studied cortical hemisphere were compared with those evoked by electrical stimulation of the contralateral cochlea with brief biphasic electrical pulses delivered via a feline cochlear prosthesis. The contralateral ear was deafened immediately before implantation of the cochlear prosthesis. The feline cochlear prosthesis consisted of four bipolar electrode pairs and was placed in the scala tympani. Two bipolar electrode conditions were used for stimulation: one near radial pair with electrode spacing of 0.25-0.5 mm, and one longitudinal pair with electrode spacing of approximately 6 mm. 2. The firing rates obtained from single- and multiple-neuron recordings were measured as a function of stimulus repetition rate of electrical and acoustic pulses. From period histograms over a recording interval of 1,000 ms, the driven firing rate to repetition rates from 2 to 38 Hz was obtained and repetition rate transfer functions (RRTFs) were constructed. The RRTFs were characterized as low-pass or band-pass filters and several descriptors were obtained, such as the repetition rate producing the highest driven activity, high and low cutoff frequencies 6 dB below maximum firing rate, and maximum firing rate. 3. For a given neuron, the main characteristics of cortical RRTFs obtained with electrical and acoustic cochlear stimulation were quite similar. However, some small but statistically significant differences in the best repetition rate, cutoff frequencies, and maximum firing rate could be observed between the different stimulation modes. The proportion of band-pass RRTFs was larger for electrical stimulation (57%) than for acoustic stimulation (41%). The high cutoff frequencies for electrical stimulation were slightly but consistently higher than for acoustic RRTFs of the same neuron and the maximum firing rate for electrical stimulation was significantly higher than that evoked by ipsilateral acoustic stimulation. 4. The entrainment of cortical neurons to electrical and acoustic pulses was determined and entrainment profiles were constructed. For a given neuron, electrical entrainment profiles showed higher cutoff frequencies than with acoustic stimulation when judged with a fixed entrainment criterion of 0.25 spikes per event. The maximum entrainment seen for electrical stimulation was approximately 20% higher than seen for the same neuron with acoustic stimulation. 5. Correlation analysis of repetition coding and latency parameters revealed several relationships between these response aspects. Most prominent among them was a significant correlation between measures of the response latency and estimates of the ability to follow temporal repetitions for acoustic as well as electrical conditions. 6. Parametric and comparative evaluations of cortical responses to acoustic and electrical cochlear stimulation support the conclusion that the temporal resolution seen in cortical neurons is largely a consequence of central processing mechanisms based on cell and circuit properties and to a lesser degree a consequence of particular spatial and temporal peripheral excitation patterns. The slightly higher temporal resolution found for the electrical stimulation modes suggests that the temporally highly coherent electrical stimulation appears to engage, in a more effective manner, the excitatory/inhibitory mechanisms contributing to the response in AI than acoustic click stimulation with less temporal coherence. (ABSTRACT TRUNCATED)


1985 ◽  
Vol 58 (4) ◽  
pp. 1122-1127 ◽  
Author(s):  
L. J. Cartier ◽  
P. D. Gollnick

Comparisons were made of the appearance of phosphorylase (PHOS) a and lactate (LA) during electrical stimulation of the gastrocnemius (GM) and soleus (SM) muscles of normal and sympathectomized (SYMPX) rats. Ten-second stimulation at 3 Hz increased PHOS a approximately fourfold in the GM of normal rats, whereafter it declined during stimulation until at 60 s it was similar to rest. The increase in PHOS a of GM from SYMPX rats after 10 s of stimulation was approximately 50% that of normal rats. Stimulation of the SM produced smaller and slower increases in PHOS a with the peak occurring after 60 s, which remained constant to 90 s. SYMPX did not alter this effect in the SM. LA production and creatine phosphate depletion in the GM were continuous throughout stimulation and uninfluenced by SYMPX. This was true for the SM with the exception of LA production being greater after SYMPX. [ATP] was unchanged by electrical stimulation. The rate and magnitude of the PHOS a appearance was a function of stimulation frequency. Reversion of PHOS to the b form after stimulation was rapid, with approximately 50% of the peak value being attained in 2.5 s, and at 5 s the values were those of rest. These data demonstrate that an intact sympathoadrenal system is not obligatory for the initiation of glycogenolysis in skeletal muscle.


1998 ◽  
Vol 80 (3) ◽  
pp. 1495-1513 ◽  
Author(s):  
Igor Timofeev ◽  
François Grenier ◽  
Mircea Steriade

Timofeev, Igor, François Grenier, and Mircea Steriade. Spike-wave complexes and fast components of cortically generated seizures. IV. Paroxysmal fast runs in cortical and thalamic neurons. J. Neurophysiol. 80: 1495–1513, 1998. In the preceding papers of this series, we have analyzed the cellular patterns and synchronization of neocortical seizures occurring spontaneously or induced by electrical stimulation or cortical infusion of bicuculline under a variety of experimental conditions, including natural states of vigilance in behaving animals and acute preparations under different anesthetics. The seizures consisted of two distinct components: spike-wave (SW) or polyspike-wave (PSW) at 2–3 Hz and fast runs at 10–15 Hz. Because the thalamus is an input source and target of cortical neurons, we investigated here the seizure behavior of thalamic reticular (RE) and thalamocortical (TC) neurons, two major cellular classes that have often been implicated in the generation of paroxysmal episodes. We performed single and dual simultaneous intracellular recordings, in conjunction with multisite field potential and extracellular unit recordings, from neocortical areas and RE and/or dorsal thalamic nuclei under ketamine-xylazine and barbiturate anesthesia. Both components of seizures were analyzed, but emphasis was placed on the fast runs because of their recent investigation at the cellular level. 1) The fast runs occurred at slightly different frequencies and, therefore, were asynchronous in various cortical neuronal pools. Consequently, dorsal thalamic nuclei, although receiving convergent inputs from different neocortical areas involved in seizure, did not express strongly synchronized fast runs. 2) Both RE and TC cells were hyperpolarized during seizure episodes with SW/PSW complexes and relatively depolarized during the fast runs. As known, hyperpolarization of thalamic neurons deinactivates a low-threshold conductance that generates high-frequency spike bursts. Accordingly, RE neurons discharged prolonged high-frequency spike bursts in close time relation with the spiky component of cortical SW/PSW complexes, whereas they fired single action potentials, spike doublets, or triplets during the fast runs. In TC cells, the cortical fast runs were reflected as excitatory postsynaptic potentials appearing after short latencies that were compatible with monosynaptic activation through corticothalamic pathways. 3) The above data suggested the cortical origin of these seizures. To further test this hypothesis, we performed experiments on completely isolated cortical slabs from suprasylvian areas 5 or 7 and demonstrated that electrical stimulation within the slab induces seizures with fast runs and SW/PSW complexes, virtually identical to those elicited in intact-brain animals. The conclusion of all papers in this series is that complex seizure patterns, resembling those described at the electroencephalogram level in different forms of clinical seizures with SW/PSW complexes and, particularly, in the Lennox-Gastaut syndrome of humans, are generated in neocortex. Thalamic neurons reflect cortical events as a function of membrane potential in RE/TC cells and degree of synchronization in cortical neuronal networks.


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