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Abstract:
The locus coeruleus (LC) and ventral tegmental area (VTA) are the source of noradrenergic and dopaminergic innervation of the medial prefrontal cortex (mPFC). These ascending projections to mPFC have been implicated in a broad range of cognitive processes in rodents and primates, but their relative contribution to mPFC function remains elusive. Determining temporal relations in spontaneous and evoked firing in the three regions is a necessary step toward understanding how the two neuromodulators might work in concert to regulate cognition.
To this end, unit activity and local field potentials were recorded simultaneously from VTA, LC and mPFC. A number of electrophysiological and pharmacological criteria were used to identify VTA and LC neurons. After a period of recording of spontaneous activity, evoked responses were elicited by electrical shock to the hind paw. Shocks were single pulses (0.5ms, 5mA) or trains of 5 pulses, delivered at 50Hz.
LC neurons responded to the single paw shock with a short latency ~ 20 ms, phasic burst, followed by brief inhibition. Trains elicited stronger responses, often biphasic, followed by prolonged inhibition. Most of the electrodes in the mPFC were located in the anterior cingulate area, where there was no response to single pulses. Trains elicited tonic excitatory responses with latencies of more than 100 ms, usually followed by inhibition, sometimes even entraining several cycles of slow oscillation. VTA neurons did not respond to the single pulse. Trains elicited excitatory responses in a small number of VTA cells, with latencies always greater than 100 ms. Both spontaneous and evoked activity of these VTA neurons was highly synchronised with mPFC activity; cortical activity always led VTA by several milliseconds.
The results confirm that the LC neurons have a very low threshold and respond with a short latency to somatosensory stimulation. Corresponding release of noradrenaline will modulate sensory responses in the target regions including mPFC and VTA. The long response latency of the VTA cells suggests that its ascending projection does not play an important role in modulating mPFC response, but rather is driven by cortex and possibly modulated by LC.
