Taurine activates GABAergic networks in the neocortex of immature mice

Bogdan A Sava,Werner Kilb,Haiyan Sun,Heiko J Luhmann,Rongqing Chen

doi:10.3389/fncel.2014.00026

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.

Highlights

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 main findings of this study can be summarized as follows: (i) bath application of 300 μM taurine increased the frequency of postsynaptic currents (PSCs) in a considerable fraction of pyramidal neurons; (ii) taurine, and glycine and isoguvacine increased the frequency of GABAA receptor mediated PSCs; (iii) these taurine-induced GABAergic PSCs mediated an excitatory effect; (iv) taurine, acting mainly on glycine receptors, induced an inward current and repetitive action potentials (APs) in GABAergic interneurons; and (v) GABAergic SP neurons do not substantially contribute to the taurine-induced activity
We conclude from these results that taurine can enhance the activity of excitatory GABAergic networks in the immature neocortex

Summary

Introduction

A variety of studies reported that ionotropic receptors for γamino butyric acid (GABA) are functionally expressed during pre- and early post-natal development (e.g., Laurie et al, 1992; Fritschy et al, 1994; Van Eden et al, 1995) and that such GABAA receptors mediate depolarizing responses in immature hippocampal (Ben-Ari et al, 1989; Rivera et al, 1999; Sipila et al, 2005) and neocortical neurons (Owens et al, 1996; Achilles et al, 2007; Ben-Ari et al, 2012). GABAA receptors are critically involved in several developmental steps (reviewed in Wang and Kriegstein, 2009), like regulating neuronal proliferation (LoTurco et al, 1995; Haydar et al, 2000), migration (Behar et al, 2000; Cuzon et al, 2006; Heck et al, 2007), neurite growth (Sernagor et al, 2010) and synaptic integration (Wang and Kriegstein, 2008) Most of these effects are mediated by tonic GABAergic activation of nonsynaptic receptors (reviewed in Kilb et al, 2013). Such early network activity probably plays an important role in the functional maturation of neocortical circuits (Ben-Ari, 2002; Spitzer, 2006; Hanganu-Opatz, 2010; Kilb et al, 2011)

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Conclusion