Anodal and cathodal tDCS modulate neural activity and selectively affect GABA and glutamate syntheses in the visual cortex of cats

KEY POINTS This study showed that anodal and cathodal transcranial direct current stimulation (tDCS) can respectively increase and decrease the amplitude of visually evoked field potentials in the stimulated visual cortex of cats, with an effect lasting for approximately 60-70 min. This study directly measured tDCS-induced changes in the concentration of inhibitory and excitatory neurotransmitters in the visual cortex using the enzyme-linked immunosorbent assay method and showed that anodal and cathodal tDCS can selectively decrease the concentration of γ-aminobutyric acid (GABA) and glutamate in the stimulated cortical area. Anodal and cathodal tDCS can selectively inhibit the synthesis of GABA and glutamate by suppressing the expression of GABA- and glutamate-synthesising enzymes, respectively. ABSTRACT Transcranial direct current stimulation (tDCS) evokes long-lasting neuronal excitability in the target brain region. The underlying neural mechanisms remain poorly understood. This study examined tDCS-induced alterations in neuronal activities as well as the concentration and synthesis of γ-aminobutyric acid (GABA) and glutamate (GLU) in area 21a (A21a) of cat visual cortex. Our analysis showed that anodal and cathodal tDCS respectively enhanced and suppressed neuronal activities in A21a, as indicated by a significantly increased and decreased amplitude of visually evoked field potentials (VEPs). The tDCS-induced effect lasted for approximately 60-70 min. In contrast, sham tDCS had no significant impact on the VEPs in A21a. On the other hand, the concentration of GABA, but not of GLU, in A21a significantly decreased after anodal tDCS relative to sham tDCS, whereas the concentration of GLU, but not of GABA, in A21a significantly decreased after cathodal tDCS relative to sham tDCS. Furthermore, the expression of GABA-synthesising enzymes GAD65 and GAD67 in A21a significantly decreased in terms of both mRNA and protein concentrations after anodal tDCS relative to sham tDCS, whereas that of GLU-synthesising enzyme glutaminase (GLS) did not change significantly after anodal tDCS. On the contrary, both mRNA and protein concentrations of GLS in A21a significantly decreased after cathodal tDCS relative to sham tDCS, while those of GAD65/GAD67 showed no significant change after cathodal tDCS. Taken together, these results indicate that anodal and cathodal tDCS may selectively reduce GABA and GLU syntheses and thus respectively enhance and suppress neuronal excitability in the stimulated brain area. This article is protected by copyright. All rights reserved.