Norepinephrine homogeneously inhibits alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate- (AMPAR-) mediated currents in all layers of the temporal cortex of the rat.

The primary auditory cortex is subject to the modulation of numerous neurotransmitters including norepinephrine (NE), which has been shown to decrease cellular excitability by yet unclear mechanisms. We investigated the possibility that NE directly affects excitatory glutamatergic synapses. We found that bath applications of NE (20 microM) decreased glutamatergic excitatory post-synaptic currents (EPSCs) in all cortical layers. Changes in the kinetics of synaptic EPSCs, invariance of pair pulse ratio and of the coefficient-of-variation, together with the decrease of responses to pressure-application of AMPA (500 microM), indicated the postsynaptic nature of the adrenergic effect. Pharmacological experiments suggested that the NE-induced depression of EPSCs is caused by the activation of alpha1 adrenoceptors, PLC, and a Ca(2+)-independent PKC. We speculate that the decrease in temporal cortex excitability might promote a posterior-to-anterior shift in cortical activation together with a decrease in spontaneous background activity, resulting eventually in more effective sensory processing.