Cellular mechanisms of long-term depression induced by noradrenaline in rat prefrontal neurons.

ABSTRACT

Noradrenaline (NA) is released in the prefrontal cortex (PFC) during salient behavioral phases and thought to modulate PFC-mediated cognitive functions. However, cellular actions of NA in PFC neurons are still not well understood. In the present study, we investigated long-term effects of bath-applied NA (12.5 min) on glutamatergic synaptic transmission in rat PFC pyramidal neurons maintained in vitro. We found that NA concentration-dependently (5 microM< or =[NA]< or =20 microM) induces long-term depression (LTD) of layer I-II to layer V pyramidal neuron glutamatergic synapses. NA acts through alpha1- and alpha2-adrenoceptors, but not beta-adrenoceptors, to induce LTD. This NA-induced LTD depends on concurrent single synaptic activations of N-methyl-d-aspartate (NMDA) receptors and requires the activation of protein kinase C and postsynaptic Extracellular signal-Regulated Kinases (ERK1/2). Western blot analyses showed that NA (20 microM for 12.5 min) indeed induces transient increases of ERK1/2 phosphorylation in PFC neurons, which is dependent at least in part on the activation of NMDA receptors and alpha1-adrenoceptors. Together, these results demonstrate that NA can lastingly depress glutamatergic synapses in rat PFC neurons through mechanisms involving alpha-adrenoceptors, NMDA receptors, and the activation of postsynaptic ERK1/2.