Norepinephrine exhibits two distinct profiles of action on sensory cortical neuron responses to excitatory synaptic...

Located within the central gray of the caudal pons, the locus coeruleus (LC) is the sole source of norepinephrine (NE) projections to the forebrain. NE is released both tonically and phasically from axonal varicosities in LC efferent target circuits. NE has been shown to produce a diverse set of actions, including suppression of spontaneous and stimulus evoked discharge, augmentation of synaptically evoked excitation, and inhibition and gating of otherwise subthreshold synaptic inputs. Utilizing an extracellular in vitro tissue slice preparation and microiontophoretic techniques, the dose-dependent actions of NE on glutamate-evoked discharges of layer II/III and layer V sensory cortical neurons were investigated. Noradrenergic effects were further examined in terms of cell and adrenoceptor specificity. The results indicate two exclusive modulatory actions of NE: 1) ejection current-dependent suppression of glutamate evoked discharge, and 2) ejection current-dependent facilitation of glutamate-evoked discharge followed by suppression of the maximal facilitated response. These effects were observed in both normal and low Ca(2+) / high Mg(2+) bathing media, suggesting a postsynaptic site for NE's actions. The facilitation of glutamate evoked discharge was selectively mimicked by the alpha-1 agonist, phenylephrine, whereas the dose-dependent suppression was mimicked by the beta-agonist isoproterenol. These results suggest that the suppressant and facilitating actions of NE are mediated by beta and alpha-1 receptors, respectively. In general, these results are consistent with previous demonstrations of NE modulatory actions on central neurons, but indicate that in the cerebral cortex these effects are both cell- and receptor-specific.