Fig. 4
Schematic of the proposed conjecture of GABAA receptors in low-dose VPA with and without add-on tPBM therapy. Dynamic changes in phasic inhibition generated by the binding of GABA (green dots) to synaptic GABAARs (depicted as light blue) and tonic inhibition caused by the binding of GABA to extrasynaptic GABAARs (dark blue) on the postsynaptic neurons of principal cells are shown. The scenarios with add-on tPBM are depicted with a light red background. a Without VPA or tPBM treatment, only PTZ was injected, and a baseline amount of GABA was released at the synaptic cleft, with some binding to synaptic GABAARs. b When parvalbumin-positive interneurons (PV-INs), the presynaptic neurons, received low-dose VPA, only a limited amount of GABA was bound to synaptic and extrasynaptic GABAARs, thus resulting in limited phasic inhibition (light blue arrow) and tonic inhibition (dark blue arrow). However, phasic inhibition only lasted for milliseconds and was already desensitized upon PTZ injection. c In the scenario of low-dose VPA with add-on tPBM, slightly more GABAs was bound to synaptic and extrasynaptic GABAARs after add-on tPBM compared with low-dose VPA without add-on tPBM. Therefore, new phasic inhibition and more tonic inhibition might contribute to the increased attenuation of SE relative to low-dose VPA without add-on tPBM. d In the high-dose VPA group, a large amount of GABA was produced and released from the axons of PV-INs. The abundant amount of GABA was not only bound to synaptic GABAARs and caused transient phasic inhibition but also effectively diffused to extrasynaptic GABAARs, thus resulting in considerable tonic inhibition after VPA injection; this long-term inhibition could last after PTZ injection, thus resulting in the longest suppression of SE. e Adding tPBM to high-dose VPA increased the preexisting large amount of presynaptic GABA production and release that were stimulated by high-dose VPA injection. A large amount of GABA was bound to synaptic GABAARs, thus resulting in high phasic inhibition, which competes with tonic inhibition and subsequently reduces phasic inhibition. Therefore, the suppression of PTZ-induced SE was inhibited. The use of the material in Fig. 4 was permitted under the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/deed.en) of the “File:1225 Chemical Synapse.jpg” from Wikimedia Commons (the free media repository [https://commons.wikimedia.org/wiki/File:1225_Chemical_Synapse.jpg]). Changes were made, and the original artwork is credited to J.G. Betts, K.A. Young, J.A. Wise, E. Johnson, B. Poe, D.H. Kruse, O. Korol, J.E. Johnson, M. Womble, P. Desaix for their “Figure 12.27 Synapse” from the Textbook OpenStax Anatomy and Physiology, published on May 18, 2016 (source: https://openstax.org/books/anatomy-and-physiology/pages/12-5-communication-between-neurons)
