Taurine activates GABAergic networks in the neocortex of immature mice

Abstract

Although it has been suggested that taurine is the main endogenous neurotransmitter acting on glycine receptors, the implications of glycine receptor-mediated taurine actions on immature neocortical networks have not been addressed yet. To investigate the influence of taurine on the excitability of neuronal networks in the immature neocortex, we performed whole-cell patch-clamp recordings from visually identified pyramidal neurons and interneurons in coronal slices from C57Bl/6 and GAD67-green fluorescent protein (GFP) transgenic mice (postnatal days 2–4). In 46% of the pyramidal neurons bath-application of taurine at concentrations ≥ 300 μM significantly enhanced the frequency of postsynaptic currents (PSCs) by 744.3 ± 93.8% (n = 120 cells). This taurine-induced increase of PSC frequency was abolished by 0.2 μM tetrodotoxin (TTX), 1 μM strychnine or 3 μM gabazine, but was unaffected by the glutamatergic antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and (±) R(-)-3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid (CPP), suggesting that taurine specifically activates GABAergic network activity projecting to pyramidal neurons. Cell-attached recordings revealed that taurine enhanced the frequency of action potentials (APs) in pyramidal neurons, indicating an excitatory action of the GABAergic PSCs. In order to identify the presynaptic targets of taurine we demonstrate that bath application of taurine induced in GAD67-GFP labeled interneurons an inward current that is mainly mediated by glycine receptors and can generate APs in these cells. We conclude from these results that taurine can enhance network excitability in the immature neocortex by selectively activating GABAergic interneurons via interactions with glycine receptors.

The building of the neocortex with non‐hyperpolarizing neurotransmitters

“…Therefore, these receptors could mediate the action of taurine as it has been shown that taurine can activate both GlyR and GABA A R (Flint et al, ; Furukawa et al, ). This is in agreement with the patch‐clamp recordings in acute cortical slices at early postnatal stages that have shown a depolarizing action of taurine mainly mediated by GlyR (Sava et al, ). In addition, taurine may contribute to maintain the high Cl – concentration by inhibiting KCC2 (Inoue et al, ) and doing so, taurine could sustain the depolarization induced by glycine and GABA and the underlying consequences.…”

Spontaneous Neuronal Activity in Developing Neocortical Networks: From Single Cells to Large-Scale Interactions

“…One possible candidate is the nonsynaptically released neurotransmitter taurine, which has been shown to mediate the propagation of excitation in the MZ via glycine receptors (Qian et al, 2014 ) and which excites CRNs (Kilb et al, 2002 ). A similar role of taurine has been described in the CP, where taurine selectively excites GABAergic interneurons in the CP, which enhance network excitability by excitatory GABAergic postsynaptic potentials (Sava et al, 2014 ). However, as the synaptic targets of neocortical CRNs have not been functionally identified yet (Kirischuk et al, 2014 ), the role of CRNs in the generation or transmission of spontaneous activity remains unclear.…”

1H-NMR and HPLC–MS/MS-based global/targeted metabolomic evaluation of Hypericum perforatum L. intervention for menopause

“…Taurine can modulate the release of inhibitory neurotransmitters for depression inhibition, and HPL can reverse this pathway to normal in a dose-dependent manner (Albrecht & Schousboe, 2005;Liu, Piao, & Li, 2013;Sava, Chen, Sun, Luhmann, & Kilb, 2014). In the process discussed earlier, the ornithine concentration exhibited a dose-dependent recovery, whereas the concentrations of urea in this pathway did not exhibit dose-dependence.…”