Serotonergic neuron diversity: Identification of raphe neurons with discharges time-locked to the hippocampal theta rhythm

摘要

The serotonergic system plays a key role in the regulation of brain states, and many of the known features of serotonergic neurons appear to match this function. Midbrain raphe nuclei provide a diffuse projection to all regions of the forebrain, and raphe neurons exhibit a slow metronome-like activity that sets the ambient levels of serotonin across the sleep–wake cycle. Serotonergic cells have also been implicated, however, in a variety of more specific functions that can hardly be related to their low-rate monotonous patterns of discharges. The amazing variety of serotonergic receptors and their type-specific distribution on cortical neurons also raise the possibility of a more intimate coordination between the activity of serotonergic neurons and their target cortical circuits. Here we report an unexpected diversity in the behavior of immunohistochemically identified serotonergic neurons. Two outstanding subpopulations were identified by using the in vivo juxtacellular recording and labeling technique. The first subpopulation of serotonergic cells exhibited the classic clock-like activity with no apparent short timescale interaction with the hippocampal electroencephalogram. The other subpopulation discharged action potentials that were phase-locked to the hippocampal theta rhythm, the oscillatory pattern associated with acquisition of information and memory formation. These results indicate that the ascending serotonergic system comprises cells involved in complex information processing beyond the regulation of state transitions. The heterogeneity of serotonergic neuron behavior can also help to explain the complexity of symptoms associated with serotonergic dysfunction.