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Neuron. 2014 Aug 6;83(3):663-78. doi: 10.1016/j.neuron.2014.07.002.

A whole-brain atlas of inputs to serotonergic neurons of the dorsal and median raphe nuclei.

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Department of Neuroscience, Karolinska Institutet, 17177 Stockholm, Sweden.
Department of Neuroscience, Karolinska Institutet, 17177 Stockholm, Sweden. Electronic address:


The serotonin system is proposed to regulate physiology and behavior and to underlie mood disorders; nevertheless, the circuitry controlling serotonergic neurons remains uncharacterized. We therefore generated a comprehensive whole-brain atlas defining the monosynaptic inputs onto forebrain-projecting serotonergic neurons of dorsal versus median raphe based on a genetically restricted transsynaptic retrograde tracing strategy. We identified discrete inputs onto serotonergic neurons from forebrain and brainstem neurons, with specific inputs from hypothalamus, cortex, basal ganglia, and midbrain, displaying a greater than anticipated complexity and diversity in cell-type-specific connectivity. We identified and functionally confirmed monosynaptic glutamatergic inputs from prefrontal cortex and lateral habenula onto serotonergic neurons as well as a direct GABAergic input from striatal projection neurons. In summary, our findings emphasize the role of hyperdirect inputs to serotonergic neurons. Cell-type-specific classification of connectivity patterns will allow for further functional analysis of the diverse but specific inputs that control serotonergic neurons during behavior.

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