Cooperation of taurine uptake and dopamine D1 receptor activation facilitates the induction of protein synthesis-dependent late LTP.
Co-activation of NMDA and dopamine receptors is required for the induction of the late phase of LTP (L-LTP) that is dependent on new protein synthesis. Other neuromodulatory substances may also contribute to this process. Here, we examined whether taurine is one of the neuromodulators contributing to L-LTP induction, since it is known that taurine uptake induces a long-lasting synaptic potentiation dependent on protein synthesis, and taurine uptake inhibition blocks L-LTP induced by tetanization. Experiments were conducted using rat hippocampal slices where field synaptic potentials were evoked and recorded in CA3-CA1 synapses. Taurine (1 mM) applied 10 min before a high frequency stimulation (HFS) train converted a transitory early-LTP (E-LTP) into an L-LTP dependent on protein synthesis. This taurine effect was blocked by a taurine uptake inhibitor. A facilitation of L-LTP induction was also obtained by pre-application of SKF38393, a D1/D5 dopamine receptor (D1R) agonist. In this case, LTP facilitation was not affected by the taurine uptake inhibitor. Nevertheless, when taurine and SKF38393 were simultaneously pre-applied at a concentration that individually did not modify E-LTP, they produced a synergistic mechanism that facilitated the induction of L-LTP with a sole HFS train. This facilitation of L-LTP was blocked by inhibiting either taurine uptake or D1R activation. Taurine and SKF38393 activated different signaling pathways to transform E-LTP into L-LTP. Taurine-induced L-LTP facilitation required MAPK activation, while D1R-agonist-induced facilitation depended mainly on PKA activation and partially on MAPK activation. On the other hand, the synergistic mechanisms induced by the cooperative action of taurine and SKF38393 were impaired by inhibitors against MAPK, PKA and PI3-K. This pharmacological profile resembles that displayed by L-LTP induced by three HFS trains at 10-min intervals. These results indicate that taurine uptake is necessary and cooperates with other neurotransmitter systems in the induction of L-LTP.
Instituto Cajal CSIC, Ave. Doctor Arce 37, Madrid 28002, Spain; Servicio de Neurobiología-Investigación, Hospital Universitario Ramón y Cajal, IRYCIS, Ctra. de Colmenar Km 9, Madrid 28034, Spain. Electronic address: luz.m.suarez@cajal.csic.es.
Luz M
LM
Suárez
Dpto. de Fisiología, Facultad Medicina, UCM, IRYCIS, Madrid 28040, Spain. Electronic address: jubustam@med.ucm.es.
Julián
J
Bustamante
Servicio de Neurobiología-Investigación, Hospital Universitario Ramón y Cajal, IRYCIS, Ctra. de Colmenar Km 9, Madrid 28034, Spain. Electronic address: luis.m.orensanz@hrc.es.
Luís M
LM
Orensanz
Servicio de Neurobiología-Investigación, Hospital Universitario Ramón y Cajal, IRYCIS, Ctra. de Colmenar Km 9, Madrid 28034, Spain. Electronic address: rafael.martin@hrc.es.
Rafael
R
Martín del Río
Servicio de Neurobiología-Investigación, Hospital Universitario Ramón y Cajal, IRYCIS, Ctra. de Colmenar Km 9, Madrid 28034, Spain. Electronic address: jose.m.solis@hrc.es.
José M
JM
Solís
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000502:physiology*; D056654:CA3 Region, Hippocampal / Q000187:drug effects / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D013654:Taurine / Q000378:metabolism*
D018491:Dopamine Agonists; D004791:Enzyme Inhibitors; D017447:Receptors, Dopamine D1; D013654:Taurine; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D019869:Phosphatidylinositol 3-Kinases; D017868:Cyclic AMP-Dependent Protein Kinases
Dopamine; Hippocampus; NMDA; SKF89976A; Slice; Taurine