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

Located within the central gray of the caudal pons, the locus coeruleus (LC ) is the sole source of norepinephrine (NE) projections to the forebrain. N E is released both tonically and phasically from axonal varicosities in LC efferent target circuits. NE has been shown to produce a diverse set of act ions, including suppression of spontaneous and stimulus evoked discharge, a ugmentation of synaptically evoked excitation, and inhibition and gating of otherwise subthreshold synaptic inputs. Utilizing an extracellular in vitr o tissue slice preparation and microiontophoretic techniques, the dose-depe ndent actions of NE on glutamate-evoked discharges of layer II/III and laye r V sensory cortical. neurons were investigated. Noradrenergic effects were further examined in terms of cell and adrenoceptor specificity. The result s indicate two exclusive modulatory actions of NE: 1) ejection current-depe ndent suppression of glutamate evoked discharge, and 2) ejection current-de pendent facilitation of glutamate-evoked discharge followed by suppression of the maximal facilitated response. These effects were observed in both no rmal and low Ca2+ / high Mg2+ bathing media, suggesting a postsynaptic site for NE's actions. The facilitation of glutamate evoked discharge was selec tively mimicked by the alpha-1 agonist, phenylephrine, whereas the dose-dep endent suppression was mimicked by the beta-agonist isoproterenol. These re sults suggest that the suppressant and facilitating actions of NE are media ted by beta and alpha-1 receptors, respectively. In general, these results are consistent with previous demonstrations of NE modulatory actions on cen tral neurons, but indicate that in the cerebral cortex those effects are bo th cell- and receptor-specific. (C) 2000 Wiley-Liss, Inc.