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Taurine Induces a Long-Lasting Increase of Synaptic Efficacy and Axon Excitability in the Hippocampus

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Taurine Induces a Long-Lasting Increase of Synaptic Efficacy and Axon Excitability in the Hippocampus The Journal of Neuroscience, January 1, 1996, 76(1):92-102 Taurine Induces a Long-Lasting Increase of Synaptic Efficacy and Axon Excitability in the Hippocampus Mario Galarreta,’ Jukn Bustamante,z Rafael Martin del Rio,’ and Josh M. Solisl Servicio de Neurobiologia, Departamento de Investigacidn, Hospital Ram& y Cajal, 28034 Madrid, and 2Depatfamento de Fisiologia, Facultad de Medicina, Universidad Complutense, 28040 Madrid, Spain The physiological role of taurine, one of the most abundant free action potential activation. In addition, taurine perfusion also amino acids in the mammalian brain, is still poorly understood. induces a long-lasting increase in intracellularly recorded We have found that bath application of the amino acid taurine EPSPs and monosynaptically activated IPSPs. A number of induces two opposite actions on field excitatory synaptic po- experimental observations such as temperature dependence, tentials (fEPSP) recorded in the CA1 area of hippocampal extracellular Na’ concentration dependence, and saturation slices: a decrease in fEPSP slope prevented by GABA, antag- studies, although they are not unequivocally conclusive, sug- onists, and a long-lasting potentiation of fEPSP independent of gest that the taurine uptake system is required for the taurine- GABA, or NMDA receptor activation. Two long-lasting pro- induced fEPSP potentiation. Our data describe a new taurine cesses account for this taurine-induced potentiation: (1) an action defined as a potentiation of synaptic transmission due in increase in synaptic efficacy that is accompanied neither by pat-t to an increment in presynaptic axon excitability and in modifications in the basic postsynaptic membrane electrical synaptic efficacy. properties nor by those presynaptic changes involved in fEPSP Key words: taurine; axon excitability; long-lasting synaptic paired-pulse facilitation; and (2) an increase in the axon excit- potentiation; EPSP; IPSP; fiber volley; taurine uptake; hip- ability revealed by a reduction in the threshold for antidromic pocampal slices In mammalianbrain, taurine (Zaminoethane sulfonic acid) is one (Huxtable, 1989). Moreover, its reported neuroinhibitory action of the most abundantfree amino acids,generally only exceededin in someareas is not specific, becauseit can be explained by the concentration by glutamate (for review, see Huxtable, 1989). At activation of GABA, or glycine receptors, as judged by the cellular levels, specific antibodiesagainst taurine have shownthat inhibition of the taurine action by specific antagonistsfor both this amino acid is presentin neurons,where it is localized in soma, receptors(Okamoto and Sakai, 1981;Horikoshi et al., 1988;Lewis dendrites, axons, and synaptic terminals, and also in glial cells et al., 1991). (Ottersen et al., 1985;Ottersen, 1988;Torp et al., 1992;Nagelhus Taurine also has been proposedas an inhibitory neuromodu- et al., 1993). Although taurine is ubiquitously and highly concen- lator, becauseit regulatescalcium fluxes in brain nerve terminals trated in the brain, its physiologicalrole is still poorly understood. (Kuriyama et al., 1978; Pasantes-Moralesand Gamboa, 1980; Moreover, it is not a protein component and it is not involved in Namima et al., 1983). In this sensetaurine has been shown to any metabolic pathway (Huxtable, 1992). reduce the releaseof severalneurotransmitters, such as noradren- One of the first proposalsof taurine function in the brain is its aline and acetylcholine from cortical slices and brain synapto- role as an inhibitory neurotransmitter. This assumptionis based somes (Kuriyama et al., 1978), GABA from cerebellar slices mainly on the observationsthat its exogenousapplication induces (Namima et al., 1983),and aspartate,glutamate, and GABA from inhibition of neuronal firing in different structures(for review, see cortical synaptosomes(Kamisaki et al., 1993). Huxtable, 1989), that it is localized in synaptic terminals (Lom- Although hippocampalslices are well suited preparations for bardini, 1976), and that a high affinity uptake systemhas been studying the electrophysiologicalaction of a neuroactive sub- demonstratedfor taurine (Lombardini, 1978; Liu et al., 1992). stance,few studieswithin this structure have been done that show However, taurine lackstwo main properties to be clearly accepted that taurine inducesan increasein chloride permeability in pyra- as a neurotransmitter: (1) it is releasedby depolarization mainly midal and granule cells (Zeise, 1985; Taber et al., 1986) . There in a calcium-independentway (Hanretta and Lombardini, 1986; are no reports even testing whether GABA, antagonistsaffect Pasantes-Moraleset al., 1988); and (2) so far the existenceof a this taurine action. Studieson other possibleactions of taurine on specific taurine receptor has not yet been demonstrated synaptic potentials are lacking. Thus, our aim hasbeen to assess these two issuesin the CA1 area of hippocampalslices. We have Received Aug. 18, 1995; revised Sept. 15, 1995; accepted Sept. 19, 1995. found that taurine inhibitory action is antagonized by GABA, This work was supported by a grant from the “Fond0 de Investigaciones Sanitarias receptor inhibitors and, even more importantly, that taurine in- de la Seauridad Social” (93/0565Y M.G. was suooorted bv a fellowshio from “Di- reccidn General de In&igaci6n ‘Cientffica y T&ica.” We’ thank Drs. k. A. Nicoll, duces a long-lasting potentiation of synaptic transmission.This D. Kullmann, and N. Men&de2 for helpful discussions and Dr. R. J. Huxtable for his last result is evidenceof a completely new action of taurine, which generous gift of GES. We also thank’ A. Latorre for technical assistance and S. we are going to study in this paper. McGrath and .I. Sealine for editorial helo. Correspondence should be addressed ;o Jose M. Solis, Ph.D., Servicio de Neuro- biologia, Departamento de InvestigacZm, Hospital Ram& y Cajal, Ctra. de Colme- MATERIALS AND METHODS nar Km 9, 28034 Madrid, Spain. Preparation of slices.Experiments were performedon transversehip- Copyright 0 1995 Society for Neuroscience 0270-6474/95/160092-11$05.00/O pocampalslices (400-500 km), obtainedfrom adult femaleSprague- Galarreta et al. l Taurine increases Synaptic Transmission J. Neurosci., January 1, 1996, 16(1):92-102 93 Dawley rats (200-250 gm), by standard procedures. Briefly, after the rat baseline the mean value of the signal, taken in a window of 2-5 msec, was decapitated, its brain was rapidly removed and dropped into ice-cold preceding the stimulus artifact. The width of the spike was taken at half standard medium (in mM): NaCl 119, NaHCO, 26.2, KCI 2.5, KH,PO, 1, of its amplitude. Data were normalized with respect to the mean values MgSO, 1.3, CaC1, 2.5, and glucose 11 pregassed with 95% OJ5% CO,. of the responses at the 20 min control period, before the application of Then the hippocampi were dissected from the surrounding tissue, and taurine. We used a program developed by one of us (J.B.) for these transversal slices were cut by a manual chopper. Before recording, the calculations. Traces shown are averages of consecutive responses, the slices were maintained in an interface holding chamber (Nicoll and Alger, number of which is indicated in every case. 1981) at room temperature (21-25°C). After at least 1 hr, a slice was Results are expressed as mean ? SEM. Statistical differences were transferred to a submersion-type recording chamber (Nicoll and Alger, assessed by one-way or two-way analyses of variance and two-tailed 1981) and continuously perfused (flow rate 1.5-2 ml/min) with the stan- Student’s t tests. dard medium equilibrated with 95% OJ5% CO,. Experiments were performed at 30-32”C, unless otherwise indicated. Solutions. Drugs applied by addition to the standard perfusion solution RESULTS included taurine, @alanine, GABA, bicuculline methiodide (BMI), picro- Effects of taurine on evoked field potentials toxin, o,L-2-amino-5-phosphonovaleric acid (APV), tetrodotoxin (TTX), 4-aminopyridine (4-AP), M-methyl-D-ghicamink chloride (all from Sigma, St. When taurine, at a concentration of 10 mM, wasbath-applied (Fig. Louis. MO). N-methvltaurine (NM-TAU) (Merck. Darmstadt. Germanv). IA) the fEPSP slopewas reduced by 30.3 ? 7.6% (n = 15) after 6-cyano-7-nitroquino~aline-2,3-hione (CNQX) (Tocris Cookion, Bristbi; 10 min of taurine perfusion. Afterwards, still in the presenceof UK or Research Biochemicals, Natick, MA), and 2-guanidinoethanesulfo- the amino acid, the fEPSP slope began to recover and regained nit acid (GES) (gift from Dr. R. .I. Huxtable, University of Arizona, Tucson, control values by approximately the end of taurine perfusion (30 AZ). The osmolarity of the perfusion solutions before and throughout the experiments were tested by a micro-osmometer (Advanced Instruments min). During taurine washout, fEPSP slope increasedprogres- Mod.3M0, Nonvood, MA). sively, reaching 67.1 + 7.3% (n = 15) over control values at -15 Extra- and intracellular recordings. To obtain evoked synaptic responses min of taurine withdrawal and remained potentiated thereafter (extra- and intracellular) in the CA1 area, Schaffer collateral-commis- for at least 1 hr. The fEPSP potentiation was dependent on the sural fibers were stimulated with electrical pulses (0.1-0.3 mA, 20-40 ksec, 0.05-0.066 Hz), applied through bipolar microelectrodes located in taurine perfusion time as illustrated in Figure 1B for the fEPSP stratum radiatum and supplied by a Grass S48 stimulator (Quincy, MA) values at 15 and 60 min of taurine washout. Short taurine perfu- or a pulse
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