Abstract Body

A striking feature of monoamine neurons in the mammalian brain is their broad reach. Although the cell bodies are clustered in discrete brainstem nuclei, their axons extend and collateralize in much of the forebrain. We have developed viral-genetic tools that allow researchers to determine, at the scale of the whole brain, population collateralization patterns as well as synaptic input to subpopulation of neurons based on their type and projection patterns (Schwarz et al., Nature 524:88, 2015). Applying these tools, we found that midbrain dopamine neurons employ an overall architecture that can be simplified as ‘biased input–segregated output’ (Beier et al., Cell 162:622, 2015; Lerner et al., Cell 162:635, 2015), whereas locus coeruleus norepinephrine neurons resemble a ‘maximal integration and broadcast’ model (Schwarz et al., 2015). More recent analyses revealed that the dorsal raphe serotonin system comprises parallel sub-systems with distinct cell body positions, axonal projection patterns, input biases, physiological response properties, and behavioral functions (Ren et al., Cell 175:472, 2018). Single-cell RNA-sequencing identified 11 transcriptomic types of serotonin neurons in dorsal and median raphe nuclei. Intersectional genetic approaches begin to match projection and gene expression patterns. For example, serotonin neurons co-expressing a vesicular glutamate transporter preferentially innervate cortical regions, whereas those co-expressing thyrotropin-releasing hormones preferentially innervate subcortical regions, in particular the hypothalamus (Ren et al., eLife 8:e49424, 2019). Systematic dissection of the monoamine systems by their gene expression and anatomical organization will be essential to understand how these neurotransmitters modulate diverse physiology and function.

Abstract Body

A striking feature of monoamine neurons in the mammalian brain is their broad reach. Although the cell bodies are clustered in discrete brainstem nuclei, their axons extend and collateralize in much of the forebrain. We have developed viral-genetic tools that allow researchers to determine, at the scale of the whole brain, population collateralization patterns as well as synaptic input to subpopulation of neurons based on their type and projection patterns (Schwarz et al., Nature 524:88, 2015). Applying these tools, we found that midbrain dopamine neurons employ an overall architecture that can be simplified as ‘biased input–segregated output’ (Beier et al., Cell 162:622, 2015; Lerner et al., Cell 162:635, 2015), whereas locus coeruleus norepinephrine neurons resemble a ‘maximal integration and broadcast’ model (Schwarz et al., 2015). More recent analyses revealed that the dorsal raphe serotonin system comprises parallel sub-systems with distinct cell body positions, axonal projection patterns, input biases, physiological response properties, and behavioral functions (Ren et al., Cell 175:472, 2018). Single-cell RNA-sequencing identified 11 transcriptomic types of serotonin neurons in dorsal and median raphe nuclei. Intersectional genetic approaches begin to match projection and gene expression patterns. For example, serotonin neurons co-expressing a vesicular glutamate transporter preferentially innervate cortical regions, whereas those co-expressing thyrotropin-releasing hormones preferentially innervate subcortical regions, in particular the hypothalamus (Ren et al., eLife 8:e49424, 2019). Systematic dissection of the monoamine systems by their gene expression and anatomical organization will be essential to understand how these neurotransmitters modulate diverse physiology and function.