Dopaminergic and noradrenergic modulation of the rat prefrontal cortex: in vivo electrophysiological study

Several investigations suggest that dopaminergic and noradrenergic neuromodulatory systems may simultaneously modulate their common targets. Moreover, the midbrain ventral tegmental area (VTA) and brain stem nucleus locus coeruleus (LC), the major sources of forebrain dopamine and noradrenaline, respectively, are reciprocally connected. The latter suggests that these two systems may be functionally interdependent. The aim of our experiments was to characterize spontaneous and evoked activity of these two neuromodulatory centers in parallel with monitoring neural activity in the medial prefrontal cortex (mPFC), their common projection structure. All experiments were performed in rats under urethane anesthesia. We recorded unit activity and local field potentials simultaneously from VTA, LC and mPFC. A number of electrophysiological and pharmacological criteria were used to distinguish VTA and LC neurons. Evoked activity was induced by a mild electrical stimulation of the hind paw. We also applied intrabrain microstimulation technique for VTA or LC regions and tested neural responses in mPFC. First, we observed a burst-like activation of LC neurons in response to hind paw stimulation with the response latency 20 ms. Brief LC activation followed by a prolonged (300 ms) inhibition. VTA neurons showed inhibitory response to the hind paw stimulation, but only if stimulation parameters were substantially stronger compared to those that activated LC (e. g. trains of pulses at 50 Hz for 100 ms). The preliminary results have not yet revealed any strong temporal relationships between spontaneous or evoked activity between VTA and LC. VTA firing may precede or follow the mPFC firing. Such response pattern may be related to the fact that VTA is a heterogeneous brain region containing dopaminergic, non-dopaminergic and GABA-ergic neurons. We plan to apply juxtacellular labeling technique in combination with immunohistochemical staining procedures in order to more reliably identify the neuronal types in VTA