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Pedagogy is the science and art of teaching. Each generation needs to explore the history, theory, and practice of the teacher-student interaction. Here we pave the path to develop a science that explores the cognitive and physiological processes involved in the human capacity to communicate knowledge through teaching. We review examples from our previous work in this research area and discuss a path to reveal the cognitive and cerebral mechanisms by which we teach, unfolding a complex operation such as teaching in its constituents and components.

Abstract: Quercetin is a natural flavonoid widely distributed in plants that acts as a neuroprotective agent and modulates the activity of different synaptic receptors and ion channels, including the ionotropic GABA receptors. GABAAρ1 receptors were shown to be antagonized by quercetin, but the mechanisms underlying these antagonistic actions are still unknown. We have analyzed here if the antagonistic action produced by quercetin on GABAAρ1 receptors was related to its redox activity or due to alternative mechanism/s. Homomeric GABAAρ1 receptors were expressed in frog oocytes and GABA-evoked responses electrophysiologically recorded. Quercetin effects on GABAAρ1 receptors were examined in the absence or presence of ascorbic acid. Chemical protection of cysteines by selective sulfhydryl reagents and site directed mutagenesis experiments were also used to determine ρ1 subunit residues involved in quercetin actions. Quercetin antagonized GABAAρ1 receptor responses in a dose-dependent, fast and reversible manner. Quercetin inhibition was prevented in the presence of ascorbic acid, but not by thiol reagents that modify the extracellular Cys-loop of these receptors. H141, an aminoacidic residue located near to the ρ1 subunit GABA binding site, was involved in the allosteric modulation of GABAAρ1 receptors by several agents including ascorbic acid. Quercetin similarly antagonized GABA-evoked responses mediated by mutant H141DGABAAρ1 and wild-type receptors, but prevention exerted by ascorbic acid on quercetin effects was impaired in mutant receptors. Taken together the present results suggest that quercetin antagonistic actions on GABAAρ1 receptors are mediated through a redox-independent allosteric mechanism. [Copyright &y& Elsevier]

Ionotropic GABA receptors (GABAA and GABAC ) belong to the Cys-loop receptor family of ligand-gated ion channels. GABAC receptors are highly expressed in the retina, mainly localized at the axon terminals of bipolar cells. Ascorbic acid, an endogenous redox agent, modulates the function of diverse proteins, and basal levels of ascorbic acid in the retina are very high. However, the effect of ascorbic acid on retinal GABA receptors has not been studied. Here we show that the function of GABAC and GABAA receptors is regulated by ascorbic acid. Patch-clamp recordings from bipolar cell terminals in goldfish retinal slices revealed that GABAC receptor-mediated currents activated by tonic background levels of extracellular GABA, and GABAC currents elicited by local GABA puffs, are both significantly enhanced by ascorbic acid. In addition, a significant rundown of GABA puff-evoked currents was observed in the absence of ascorbic acid. GABA-evoked Cl- currents mediated by homomeric ρ1 GABAC receptors expressed in Xenopus laevis oocytes were also potentiated by ascorbic acid in a concentration-dependent, stereo-specific, reversible, and voltage-independent manner. Studies involving the chemical modification of sulfhydryl groups showed that the two Cys-loop cysteines and histidine 141, all located in the ρ1 subunit extracellular domain, each play a key role in the modulation of GABAC receptors by ascorbic acid. Additionally, we show that retinal GABAA IPSCs and heterologously expressed GABAA receptor currents are similarly augmented by ascorbic acid. Our results suggest that ascorbic acid may act as an endogenous agent capable of potentiating GABAergic neurotransmission in the CNS. [ABSTRACT FROM AUTHOR]

The activity of many receptors and ion channels in the nervous system can be regulated by redox-dependent mechanisms. Native and recombinant GABAA receptors are modulated by endogenous and pharmacological redox agents. However, the sensitivity of GABAC receptors to redox modulation has not been demonstrated. We studied the actions of different reducing and oxidizing agents on human homomeric GABAρ1 receptors expressed in Xenopus laevis oocytes. The reducing agents dithiothreitol (2 mM) and N-acetyl-l-cysteine (1 mM) potentiated GABA-evoked Cl− currents recorded by two-electrode voltage-clamp, while the oxidants 5-5′-dithiobis-2-nitrobenzoic acid (500 μM) and oxidized dithiothreitol (2 mM) caused inhibition. The endogenous antioxidant glutathione (5 mM) also enhanced GABAρ1 receptor-mediated currents while its oxidized form GSSG (3 mM) had inhibitory effects. All the effects were rapid and easily reversible. Redox modulation of GABAρ1 receptors was strongly dependent on the GABA concentration; dose–response curves for GABA were shifted to the left in the presence of reducing agents, whereas oxidizing agents produced the opposite effect, without changes in the maximal response to GABA and in the Hill coefficient. Our results demonstrate that, similarly to GABAA receptors and other members of the cys-loop receptor superfamily, GABAC receptors are subjected to redox modulation. [ABSTRACT FROM AUTHOR]