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Abstract

Salient events evoke burst-like responses of noradrenergic (NE) neurons of the Locus Coeruleus (LC) and dopaminergic (DA) neurons of the ventral tegmental area (VTA). The associated NE and DA release modulates signal processing in the projection targets of LC and VTA, which is beneficial for selection of adaptive behavioral response. In the rat, terminal fields of both LC-NE and VTA-DA neurons converge in the medial prefrontal cortex (mPFC), a cortical area controlling many cognitive capacities. We investigated the role of LC phasic activation for sensory representations in two LC targets by simultaneous electrophysiological recording in LC, VTA and mPFC and pharmacological manipulation of LC activity. Under urhetaine anestesia, noxious stimulation (foot shock, FS) produces a robust short-latency (~20 ms) excitation/inhibition response of LC-NE neurons. Populations of VTA and mPFC neurons also exhibit phasic excitatory and inhibitory responses, yet with longer latencies (~100 ms). Supression of LC spontaneous and evoked activity by iontophoretic injection of clonidine, an alpha2-adrenergic receptor agonist, disinibited a substantial proportion of VTA-DA and mPFC pyramidal neurons regardless of their FS-responsiveness. Furthermore, LC inhibition bidirectionally modulated the VTA-DA and mPFC resposes to noxious stimulation. The ongoing and evoked activity of VTA non-DA neurons was unaffected. These results suggest that depending on the motivational valence of a salient event, the LC-NE system may selectively enhance or supress signalling within different and, possibly, competing mesolimbic and mesocortical pathways. This hypothesis is being currently tested in behaving animals engaiged in a sensory cue-guided reward-motivated operant task.