Dysfunction in serotonin system is involved in multiple mental diseases, especially mood disorders. The antidepressant drug Fluoxetine (Prozac), for example, is a selective serotonin reuptake inhibitor. The dorsal raphe nucleus (DRN) contains most of the forebrain-projecting serotonergic neurons, and is thought to be important for numerous cognitive processes. However, the circuit mechanisms underlying the controlling of serotonergic neurons in the DRN remain elusive.
A recent study published in Cell Reports systematically analyzed the circuit mechanism underlying dynamic control of serotonergic neuron in the rodent brain. Dr. SUN Yangang鈥檚 Lab at the Institute of Neuroscience of Chinese Academy of Sciences used adeno-associated virus (AAV) tracing and patch clamp recording combined with optogenetic method in brain slices to explore the functional inputs to serotonergic neurons, and uncovered organizing principles of long-range inputs to the serotonergic neurons.
To reveal this mechanism, SUN's lab systematically examined the property of six key upstream brain areas of DRN serotonergic neurons, including prefrontal cortex (PFC), lateral habenula (LHb), lateral hypothalamus (LH), preoptic area (POA), substantia nigra (SN), and amygdala. They found that all of the key upstream brain areas provided direct synaptic input to serotonergic neurons. These brain areas showed different topographic innervation patterns including both bilateral axonal innervation patterns (PFC and LHb) and unilateral innervation patterns (LH, POA, SN, and amygdala).
Also, they demonstrated that these upstream brain areas controlled the activity of serotonergic neurons with two distinct strategies. One group of brain areas employed a push-pull mechanism, where a single brain area provided both excitatory and inhibitory inputs onto individual serotonergic neurons. The other group of brain areas sent only excitatory projections to serotonergic neurons, and independently recruited feedforward inhibition for bidirectional control of the activity of serotonergic neurons.
This study successfully determined the organizing principle of long-range circuits controlling the activity of serotonergic neurons, and advanced the understanding of the mechanisms regulating the serotonin system, which could have important impact on the mechanisms of mental disorder.
This study was supported by the National Natural Science Foundation of China, Chinese Academy of Sciences Hundreds of Talents Program, Youth Thousand Plan, and the Strategic Priority Research Program of the Chinese Academy of Sciences.
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