Neural coding in medial prefrontal cortex (mPFC) is thought to underlie various cognitive behaviors such as rule-guided learning, strategy use, or cognitive flexibility. Specifically, prefrontal neurons display many behaviorally relevant correlates related to sensory perception, motor responses, or reward that are believed to contribute to behavioral outcome. The mPFC is the cortical region that receives exceptionally dense dopaminergic (DA) innervation arising from the mesopontine Ventral Tegmental Area (VTA). Noradrenergic fibers originating from the brain stem nucleus Locus Coeruleus (LC) are also dense in mPFC. Previous investigations indicated that NA and DA systems have common target neurons in mPFC. The ascending NA and DA projections to mPFC have been implicated in a broad range of cognitive processes in rodents and primates including modulation of perception, attention, motivation, or memory. It is still, however, unknown whether and how NA and DA affect the prefrontal neural codes. To address this question, we performed simultaneous recordings of unit activity and local field potentials in mPFC, VTA and LC in the rat. We first studied temporal relations of firing activity in the three brain regions during spontaneous and evoked activity under anesthesia. Mild electric shocks were applied to the rat hind paw for somatosensory stimulation. The LC neurons responded to a single foot shock (1ms, 5mA) with a short latency (~20ms), phasic burst, followed by brief inhibition. Trains of pulses (100ms, 50Hz, 5mA) elicited much stronger responses. The mPFC and VTA neurons did not respond to a single foot shock. Trains elicited sustained (~1s) excitatory responses in a subpopulation of mPFC neurons with latencies of ~100ms, usually followed by inhibition. Trains elicited both excitatory and inhibitory responses in a small number of putative dopaminergic, VTA cells, with latencies always greater than 100ms. Both spontaneous and evoked activity of VTA neurons was highly synchronized with mPFC activity; cortical activity always led VTA by several milliseconds. In some cases, sensory stimulation resulted in entrainment of mPFC and VTA neurons in several cycles of slow oscillation. Next, we inhibited the LC by systemic or local application of clonidine, an α2-adrenergic receptor agonist. This manipulation dramatically abolished the excitatory evoked responses in both VTA and mPFC without having much effect on spontaneous activity. The results indicate that short-latency responses of LC neurons to somatosensory stimulation with corresp