Modulation Of Long-term Plasticity Research Articles

Involvement of P2Y1, P2Y6, A1 and A2A Receptors in the Purinergic Inhibition of NMDA-Evoked Noradrenaline Release in the Rat Brain Cortex.

In the cerebral cortex, glutamate activates NMDA receptors (NMDARs), localized in noradrenergic neurons, inducing noradrenaline release that may have a permissive effect on glutamatergic transmission, and therefore, on the modulation of long-term plasticity. ATP is co-released with noradrenaline, and with its metabolites (ADP and adenosine) is involved in the purinergic modulation of electrically-evoked noradrenaline release. However, it is not known if noradrenaline release evoked by activation of NMDARs is also under purinergic modulation. The present study aimed to investigate and to characterize the purinergic modulation of noradrenaline release evoked by NMDARs. Stimulation of rat cortical slices with 30 µM NMDA increased noradrenaline release, which was inhibited by ATP upon metabolization into ADP and adenosine and by the selective agonists of A1 and A2A receptors, CPA and CGS2680, respectively. It was also inhibited by UTP and UDP, which are mainly released under pathophysiological situations. Characterization of the effects mediated by these compounds indicated the involvement of P2Y1, P2Y6, A1 and A2A receptors. It is concluded that, in the rat brain cortex, NMDA-evoked noradrenaline release is modulated by several purinergic receptors that may represent a relevant mechanism to regulate the permissive effect of noradrenaline on NMDA-induced neuroplasticity.

Modulation of long-term synaptic plasticity at excitatory striatal synapses

Modulation of long-term plasticity by both the intrinsic activation of metabotropic glutamate receptors and dopamine released from the nigrostriatal pathway was investigated at excitatory striatal synapses. Intracellular recordings demonstrated that tetanic stimulation at an intensity equal to that used for synaptic sampling produced, on average, a slight long-term depression of excitatory postsynaptic potentials. The long-term response pattern was variable, however, with some cells showing potentiation and others no plasticity. Block of metabotropic glutamate receptors with 3-aminophosphonovaleric acid changed the pattern of responses, increasing the percentage of cells showing long-term potentiation. Similarly, 6-hydroxydopamine lesions to the substantia nigra changed the pattern of response to tetanic stimulation, increasing the expression of long-term potentiation. These data indicate that metabotropic glutamate receptor and dopamine receptor activation may function to regulate the expression of activity-dependent plasticity at corticostriatial synapses. Paired-pulse stimulation revealed that post-tetanic plasticity was negatively correlated with changes in paired-pulse plasticity in the control and 6-hydroxydopamine-lesioned groups, suggesting that the expression of long-term plasticity has a presynaptic component at corticostriatal synapses.