nitroarginine and saclofen

A fundamental issue in understanding activity-dependent long-term plasticity of neuronal networks is the interplay between excitatory and inhibitory synaptic drives in the network. Using dual whole-cell recordings in cultured hippocampal neurons, we examined synaptic changes occurring as a result of a transient activation of NMDA receptors in the network. This enhanced transient activation led to a long-lasting increase in synchrony of spontaneous activity of neurons in the network. Simultaneous long-term potentiation of excitatory synaptic strength and a pronounced long-term depression of inhibitory synaptic currents (LTDi) were produced, which were independent of changes in postsynaptic potential and Ca2+ concentrations. Surprisingly, miniature inhibitory synaptic currents were not changed by the conditioning, whereas both frequency and amplitudes of miniature EPSCs were enhanced. LTDi was mediated by activation of a presynaptic GABAB receptor, because it was blocked by saclofen and CGP55845 [(2S)-3-{[(15)-1-(3, 4-dichlorophenyl)ethyl]amino-2-hydroxypropyl)(phenylmethyl)phosphinic acid]. The cAMP antagonist Rp-adenosine 3 ', 5 ' -cyclic monophosphothioate abolished all measured effects of NMDA-dependent conditioning, whereas a nitric oxide synthase inhibitor was ineffective. Finally, network-induced plasticity was not occluded by a previous spike-timing-induced plasticity, indicating that the two types of plasticity may not share the same mechanism. These results demonstrate that network plasticity involves opposite affects on inhibitory and excitatory neurotransmission.

Topics: 2-Amino-5-phosphonovalerate; Animals; Baclofen; Calcium; Cells, Cultured; Colforsin; Cyclic AMP; Evoked Potentials; Hippocampus; Long-Term Potentiation; Long-Term Synaptic Depression; Neuronal Plasticity; Neurons; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; Patch-Clamp Techniques; Phosphinic Acids; Propanolamines; Quinoxalines; Rats; Receptors, GABA-B; Receptors, N-Methyl-D-Aspartate; Synaptic Transmission; Tetrodotoxin; Thionucleotides; Time Factors