6-cyano-7-nitroquinoxaline-2-3-dione and 9-(tetrahydro-2-furyl)-adenine

Dopamine has been implicated in various brain functions and the pathology of neurological diseases. In the hippocampus, dopamine has been shown to induce acute depression of synaptic transmission in the CA1 region, but it remains largely unknown how it works in the CA3 region. We here report that dopamine induces acute synaptic potentiation at the synapse formed by mossy fibers (MFs) on mouse hippocampal CA3 pyramidal cells, but not at converging associational/commissural synapses. Dopamine potentiated both alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-d-aspartate (NMDA) components of MF synaptic responses similarly in respect of the magnitude and time course. The dopamine-induced potentiation was intact in the presence of picrotoxin, required activation of D(1)-like receptors and was apparently occluded by an activator of adenylate cyclase. The potentiation was accompanied by a decrease in magnitude of synaptic facilitation, suggesting the presynaptic site for the expression of the potentiation. The present study is the first demonstration of acute potentiation of hippocampal excitatory synaptic transmission by dopamine, which is most probably mediated by presynaptic D(1)-like receptor-cAMP cascades.

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Adenine; Animals; Dopamine; Dopamine Agonists; Dose-Response Relationship, Drug; Electric Stimulation; Enzyme Inhibitors; Excitatory Amino Acid Antagonists; Excitatory Postsynaptic Potentials; Hippocampus; In Vitro Techniques; Male; Mice; Mossy Fibers, Hippocampal; Patch-Clamp Techniques; Pyramidal Cells; Synaptic Transmission

Activity-dependent long-term potentiation (LTP) in the CNS is thought to be important in learning, memory, development, and persistent pain. Here, we report that NMDA receptor-dependent LTP is the major form of long-term plasticity in the anterior cingulate cortex (ACC). In addition to N-methyl-D-aspartate (NMDA) receptors, L-type voltage-gated calcium channels are also required for inducing LTP. Activation of calcium-stimulated adenylyl cyclase subtype 1 (AC1) is essential for the induction of LTP in ACC neurons, while AC8 subunit partially contributes to forskolin-induced potentiation. Our results suggest that calcium-stimulated cAMP-dependent signaling pathways play a critical role in cingulate LTP.

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Adenine; Adenylyl Cyclases; Animals; Calcium; Calcium Channel Blockers; Colforsin; Dose-Response Relationship, Drug; Drug Interactions; Electric Stimulation; Enzyme Inhibitors; Excitatory Amino Acid Agonists; Excitatory Amino Acid Antagonists; GABA Antagonists; Gyrus Cinguli; In Vitro Techniques; Long-Term Potentiation; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Nifedipine; Patch-Clamp Techniques; Picrotoxin; Synaptic Transmission; Time Factors; Valine