The damage to dendrites and spines would result in decreased neuronal activity. Therefore, the decreased LFP response following 0. Hence, our results may provide some indication for the use of tPCS in animal and human studies. The calcium response can be reliably detected in neurogliopil region, which contains many fine processes of the surrounding neurons and astrocytes.
In these places, astrocyte processes closely interact with neuronal synapses and modulate synaptic transmission and plasticity Araque et al. The brain function arises from the coordinated activity of neuron-glia networks Perea et al. Many studies reported that tPCS can modulate brain oscillatory activity and enhance functional connectivity Guleyupoglu et al.
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Due to the different recording methods, the calcium activity observed in our experiments cannot be directly compared with their results, which were mainly based on EEG recording. In short, we cannot rule out the possibility that the neurogliopil response may also play a role in a-tPCS-induced plasticity. The findings in this study should be considered in the context of several limitations. Firstly, we acknowledge that the IP 3 R2 inositol trisphosphate receptor type 2 knockout mice should be used to prove the involvement of astrocytic GPCR G-protein-coupled receptor activation Monai et al.
However, the pharmacological experiments using prazosin demonstrated the involvement of noradrenergic activation of A1ARs, which transduce the G q signaling cascade for production of IP 3. Some related studies have demonstrated that synaptic plasticity in layer 4 disappears as the animal matures after the critical period Daw et al. In this study, the depth of imaging is limited to the superficial layers layers 1—3 of the cortex. Therefore, the findings in the current study are only pertinent to the superficial layers of the cortex.
Thirdly, the anodal current stimulation generally enhances cortical excitability. However, the a-tPCS involves the injection of much monopolar current. Compared to a-tPCS, transcranial alternating current stimulation tACS is a balanced current consisting of bipolar alternating current with equal electric charge.
No irreversible electrochemical products are known to accumulate at the electrode Antal et al.
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When considering translational validity in humans, a balanced tACS protocol might be an alternative. In short, the a-tPCS parameters in our study should be adjusted carefully when directly translated into the clinical conditions.
In summary, the calcium response in mouse somatosensory cortex evoked by long-duration a-tPCS was reported for the first time. The decrease of cortical excitability induced by high-intensity a-tPCS may be caused by excessive calcium activity in neurons. These findings would contribute to the understanding of mechanisms underlying a-tPCS-induced cortical plasticity, and also suggest that the appropriate current intensity should be used in the application of a-tPCS. ZM and HS designed the experiments. ZM and HS wrote the manuscript. All authors reviewed the manuscript.
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