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

Neuroscience. 2010 Aug 11;169(1):74-86. doi: 10.1016/j.neuroscience.2010.04.046. Epub 2010 Apr 29.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic Agents / pharmacology
  • Afferent Pathways / physiology
  • Animals
  • Excitatory Postsynaptic Potentials / drug effects
  • Extracellular Signal-Regulated MAP Kinases / physiology
  • Long-Term Synaptic Depression / drug effects*
  • Male
  • Neurons / drug effects*
  • Neurons / physiology
  • Norepinephrine / pharmacology*
  • Prefrontal Cortex / drug effects*
  • Prefrontal Cortex / growth & development
  • Prefrontal Cortex / physiology
  • Protein Kinase C / physiology
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Adrenergic, alpha-1 / drug effects
  • Receptors, Adrenergic, alpha-1 / physiology
  • Receptors, Adrenergic, alpha-2 / drug effects
  • Receptors, Adrenergic, alpha-2 / physiology
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Temperature


  • Adrenergic Agents
  • Receptors, Adrenergic, alpha-1
  • Receptors, Adrenergic, alpha-2
  • Receptors, N-Methyl-D-Aspartate
  • Protein Kinase C
  • Extracellular Signal-Regulated MAP Kinases
  • Norepinephrine