Suppression of noradrenergic and dopaminergic neurotransmission differentially affects detection of behaviorally relevant auditory stimuli

Both central noradrenergic (NE) and dopaminergic (DA) neuromodulatory systems are involved in processing of behaviorally relevant sensory stimuli. The brain stem nucleus Locus Coeruleus (LC) is activated by sensory stimulation and associated NE release in the LC forebrain targets modulates feed-forward sensory processing. The DA neurons of the midbrain ventral tegmental area (VTA) are responsive to reward-predicting stimuli and associated DA release facilitates reorganization of their neural representations. The specific contribution of NE and DA transmission for sensory processing in the higher-order cortical areas like the medial Prefrontal Cortex (mPFC) is less understood. We trained rats to detect a reward predicting frequency modulated target sound out of a sequence of pure tones (8, 12, 14 and 16 kHz) in the operant chamber. Four frequency modulation magnitudes were used: 0, 5, 30 and 100. After reaching the learning criterion, the rats were implanted with bilateral chronic cannulas in the VTA and/or LC. The rat performance was tested after injection of Clonidine, an alpha2-noradrenergic-Agonist, into LC (25ng, 500nl) or U69593, a Kappa-Opioid-Agonist, into VTA (320ng, 500nl). Preliminary results indicated that decreased DA transmission within the VTA-mPFC pathway by U69593-infusion increased the reaction time regardless of the magnitude of frequency modulation of the target sound. Suppression of LC activity by clonidine-infusion impaired only detection of sounds with 5 frequency modulation. Our results suggest that DA release in the mPFC is critical for executive control of signal detection regardless of the signal detection threshold, while NE release is important for lowering the detection threshold