Despite the well-established role of serotonin signaling in mood regulation, causal relationships between serotonergic neuronal activity and behavior remain poorly understood.
Low levels of serotonin in the brain are known to play a role in depression and anxiety, and it is customary to treat these disorders with medications that increase the amount of this neurotransmitter. However, a new study suggests that this approach may be too simple. It appears that neighboring serotonin-producing brainstem regions exert different and sometimes opposing effects on behavior.
Researchers knew that the brainstem contains two distinct clusters of serotonergic neurons: one in dorsal raphe nucleus (DRN) and another in the median raphe nucleus (MRN). Together both regions harbor the vast majority of neurons that supply serotonin to the rest of the brain, but it was unclear how neuronal activity within these clusters controls behavior.
Using a pharmacogenetic approach, researchers find that selectively increasing serotonergic neuronal activity in wild-type mice is anxiogenic and reduces floating in the forced-swim test, whereas inhibition has no effect on the same measures.
In a developmental mouse model of altered emotional behavior, increased anxiety and depression-like behaviors correlate with reduced dorsal raphé and increased median raphé serotonergic activity. These mice display blunted responses to serotonergic stimulation and behavioral rescues through serotonergic inhibition.
Furthermore, scientists identify opposing consequences of dorsal versus median raphé serotonergic neuron inhibition on floating behavior, together suggesting that median raphé hyperactivity increases anxiety, whereas a low dorsal/median raphé serotonergic activity ratio increases depression-like behavior.
Thus, authors find a critical role of serotonergic neuronal activity in emotional regulation and uncover opposing roles of median and dorsal raphé function.
http://www.cell.com/cell-reports/abstract/S2211-1247(15)01250-4
Edited
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