Cortical Plasticity Induced by Anodal Transcranial Pulsed Current Stimulation Investigated by Combining Two-Photon Imaging and Electrophysiological Recording

Abstract

Anodal-transcranial pulsed current stimulation (a-tPCS) has been used in human studies to modulate cortical excitability or improve behavioral performance in recent years. Multiple studies show crucial roles of astrocytes in cortical plasticity. The calcium activity in astrocytes could regulate synaptic transmission and synaptic plasticity. Whether the astrocytic activity is involved in a-tPCS-induced cortical plasticity is presently unknown. The purpose of this study is to investigate the calcium responses in neurons and astrocytes evoked by a-tPCS with different current intensities, and thereby provides some indication of the mechanisms underlying a-tPCS-induced cortical plasticity. Two-photon calcium imaging was used to record the calcium responses of neurons and astrocytes in mouse somatosensory cortex. Local field potential (LFP) evoked by sensory stimulation was used to assess the effects of a-tPCS on plasticity. We found that long-duration a-tPCS with high-intensity current could evoke large-amplitude calcium responses in both neurons and astrocytes, whereas long-duration a-tPCS with low-intensity current evoked large-amplitude calcium responses only in astrocytes. The astrocytic Ca 2+ elevations are driven by noradrenergic-dependent activation of the alpha-1 adrenergic receptors (A1ARs), while the intense Ca 2+ responses of neurons are driven by action potentials. LFP recordings demonstrated that low-intensity a-tPCS led to enhancement of cortical excitability while high-intensity a-tPCS resulted in diminution of cortical excitability. The results provide some evidence that the enhancement of a-tPCS-induced cortical excitability might be partly associated with calcium elevation in astrocytes, whereas the diminution of a-tPCS-induced cortical excitability might be caused by excessive calcium activity in neurons. These findings indicate that the appropriate current intensity should be used in the application of a-tPCS.

Novel Non-invasive Transcranial Electrical Stimulation for Parkinson’s Disease

“…Different from conventional tDCS, tPCS provides discontinuous direct current interrupted by either short or long periodical inter-pulse intervals ( Ma et al, 2019 ), thus adding two additional parameters: inter-pulse intervals and pulse durations. Although phosphene might also be induced by tPCS, the overall tolerability toward tPCS is better than tDCS in healthy subjects, with a significantly reduced feeling of itching, tingling, and eye flashing ( Jaberzadeh et al, 2014 ).…”

Non-invasive Transcranial Electrical Stimulation in Movement Disorders

“…The intensity-specific modulation of cortical excitability by tPCS has been addressed recently by Ma et al (2019). Enhancement of cortical excitability by low-intensity anodal tPCS is likely related to astrocytic Ca 2+ elevations due to the noradrenergic activation of alpha-1 adrenergic receptors, but high-intensity anodal tPCS decrease cortical excitability with excessive calcium activity in neurons.…”

MEMS Enabled Miniature Two-Photon Microscopy for Biomedical Imaging

“…With the help of genetically encoded calcium indicators (GECIs) [ 9 , 10 ], TPM has revolutionized the field of calcium imaging in living animals [ 11 , 12 , 13 ]. For example, TPM has been used to study neuronal activity [ 14 , 15 , 16 ], neuronal plasticity [ 17 , 18 ], and neurodegenerative diseases [ 19 , 20 ]. To obtain stable in vivo brain imaging and study the neuron activities in a relatively large depth, head fixation is deployed for a conventional bench-top TPM in which the head of a small animal is constrained under the two-photon microscopy objective [ 16 ].…”