Abstract
Alterations in the development of the serotonin system can have prolonged effects including depression and anxiety disorders later in life. Serotonin axonal projections from the dorsal raphe undergo extensive refinement during the first two weeks of postnatal life in rodents (equivalent to the 3rd trimester of human pregnancy). However, little is known about the functional properties of serotonin and GABA neurons in the dorsal raphe during this critical developmental period. We assessed the functional properties and synaptic connectivity of putative serotoninergic neurons and GABAergic neurons in the dorsal raphe during early (postnatal day (P) P5-P7) and late (P15-P17) stages of the 3rd trimester-equivalent period using electrophysiology. Our studies demonstrate that GABAergic neurons are hyperexcitable at P5-P7 relative to P15-P17. Furthermore, putative serotonin neurons exhibit an increase in both excitatory and GABAA receptor-mediated spontaneous postsynaptic currents during this developmental period. Our data suggest that GABAergic neurons and putative serotonin neurons undergo significant electrophysiological changes during neonatal development.
Significance Statement: During development serotonin plays a major role in neuronal proliferation and differentiation, axonal migration, and synaptogenesis. However, the understanding of the functional development of this neurotransmitter system is limited. We characterized the functional properties of developing GABAergic and serotoninergic neurons in the dorsal raphe that release 5-HT into many forebrain regions. Our studies indicate that both GABAergic and serotoninergic neurons undergo significant functional maturation during the first two postnatal weeks in mice. Therefore, alterations of the serotonin system induced by stress, drugs, or anti-depressants during this critical period could have deleterious effects within the dorsal raphe as well as other brain regions innervated by serotoninergic axons.
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