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Abstract:
The Locus Coeruleus (LC) is a major source of noradrenaline (NE) for the cerebral cortex. Tonic stimulation of LC
typically results in desynchronization of the forebrain EEG and priming phasic activation of LC increases signalto-
noise ratio of sensory cortical and thalamic neurons. Although electrical microstimulation is commonly used, its
effects on LC neuronal discharge have not been studied systematically. We sought to compare the local effects
of LC microstimulation and its effects on neural activity of its distal cortical targets. We performed a combined
recording/stimulation study in urethane-anesthetized rats. We applied monopolar stimulation of LC, delivering biphasic single-pulses (SP, duration range: 0.1-0.5ms; amplitude range: 0.01-0.2mA) and 50-200ms trains of pulses (TR) at 20-50Hz every 4s. Neural activity in the stimulated LC, the contralateral LC and ipsilateral mPFC was recorded simultaneously. LC neurons in close proximity to the stimulation site showed a long-lasting inhibition after SP with no spikes for 40-120ms depending on the stimulation current. Duration of inhibition well exceeded a ~20ms artifact period and decreased at higher currents (196±10ms at 0.01-0.05mA; 131±12ms at 0.07-0.2mA, n=7, p<0.001). There was no effect of pulse duration. Neural responses in the contralateral LC showed overall a shorter inhibition (65±6ms). None of the SP affected the firing rate of the ispilateral prefrontal (mPFC) neurons. TR elicited a sustained inhibition in the stimulated LC (488±63ms at 20Hz and 869±69ms at 50Hz, n=4, p<0.001). Preliminary analysis revealed no effect in the contralateral LC and mPFC except for occasional brief excitation. In agreement with earlier observations, only relatively long (~500ms) TR affected cortical activity as detected by a transient desynchronization in mPFC. Our results show that a wide range of stimulation parameters may mimic characteristic response of the noradrenergic LC neurons to salient stimuli (a brief excitation followed by a prolonged inhibition), while only relatively strong LC stimulation may affect neural activity in distal cortical targets of LC. Thus, LC microstimulation can be effectively used for phasic activation of LC-NE system in a well-controlled mode in behavioral studies, but careful examination of effects of LC stimulation in the region of interest is essential for the interpretation of results.
