Cellular mechanisms of long-term depression induced by noradrenaline in rat prefrontal neurons.
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.
Marzo
A
A
Laboratory of Neuromodulation, Neuronal Plasticity and Cognition, Centre National de la Recherche Scientifique-Unité Mixte de Recherhe (CNRS-UMR) 7102, University of Pierre and Marie Curie-Paris 6, 7 quai Saint Bernard, 75005 Paris, France.
Bai
J
J
Caboche
J
J
Vanhoutte
P
P
Otani
S
S
D018663:Adrenergic Agents / Q000494:pharmacology; D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D036881:Long-Term Synaptic Depression / Q000187:drug effects*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000502:physiology; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology; D013696:Temperature
D018663:Adrenergic Agents; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D016194:Receptors, N-Methyl-D-Aspartate; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D009638:Norepinephrine