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Review
. 2011 Dec 1:197:17-27.
doi: 10.1016/j.neuroscience.2011.08.061. Epub 2011 Aug 30.

Molecular genetics of mouse serotonin neurons across the lifespan

E S Deneris  1
Affiliations
Review

Molecular genetics of mouse serotonin neurons across the lifespan

E S Deneris. Neuroscience. .

Abstract

New molecular genetics approaches have been developed over the past several years to study brain serotonin (5-HT) neuron development and the roles of 5-HT neurons in behavior and physiology. These approaches were enabled by manipulation of the gene encoding the Pet-1 ETS transcription factor whose expression in the brain is restricted to developing and adult 5-HT neurons. Targeting of the Pet-1 gene led to the development of a mouse line with a severe and stable deficiency of embryonic 5-HT-synthesizing neurons. The Pet-1 transcription regulatory region has been used to create several new 5-HT neuron-type transgenic tools that have greatly increased the experimental accessibility of the small number of brain 5-HT neurons. Permanent and specific marking of 5-HT neurons with Pet-1-based transgenic tools have now been used for flow cytometry, whole cell electrophysiological recordings, progenitor fate mapping, and live time lapse imaging of these neurons. Additional tools provide multiple strategies for conditional temporal targeting of gene expression in 5-HT neurons at different stages of life. Pet-1-based approaches have led to advances in understanding the role of 5-HT neurons in respiration, thermoregulation, emotional behaviors, maternal behavior, and the mechanism of antipsychotic drug actions. In addition, these approaches have begun to reveal the molecular basis of 5-HT neuron heterogeneity and the transcriptional mechanisms that direct 5-HT neuron-type identity, maturation, and maintenance.

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Figures

Figure 1
Figure 1
Anti-5-HT immunoreactivity in the wild type (left) and Pet-1−/− (right) anterior hindbrain at E11.5. Scale bar: 100 μm.
Figure 2
Figure 2
A 40 kilobase mouse Pet-1 upstream genomic fragment directs LacZ transgene expression to virtually all 5HT neurons in the adult midbrain, pons and medulla. Scale bars: A, E, 200 μm; B–D, 100 μm. B1, raphe pallidus; B2, raphe obscurus; B3, ventrolateral medulla; B5, pontine median raphe; B6, pontine dorsal raphe; B7, midbrain dorsal raphe; B8, midbrain median raphe.
See this image and copyright information in PMC

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