Development of Serotonergic Fibers in the Post-Natal Mouse Brain

Abstract

Serotonin (5-HT)-synthetizing neurons, which are confined in the raphe nuclei of the rhombencephalon, provide a pervasive innervation of the central nervous system (CNS) and are involved in the modulation of a plethora of functions in both developing and adult brain. Classical studies have described the post-natal development of serotonergic axons as a linear process of terminal field innervation. However, technical limitations have hampered a fine morphological characterization. With the advent of genetic mouse models, the possibility to label specific neuronal populations allowed the rigorous measurement of their axonal morphological features as well as their developmental dynamics. Here, we used the Tph2GFP knock-in mouse line, in which GFP expression allows punctual identification of serotonergic neurons and axons, for confocal microscope imaging and we performed 3-dimensional reconstruction in order to morphologically characterize the development of serotonergic fibers in specified brain targets from birth to adulthood. Our analysis highlighted region-specific developmental patterns of serotonergic fiber density ranging from a linear and progressive colonization of the target (Caudate/Putamen, Basolateral Amygdala, Geniculate Nucleus and Substantia Nigra) to a transient increase in fiber density (medial Prefrontal Cortex, Globus Pallidus, Somatosensory Cortex and Hippocampus) occurring with a region-specific timing. Despite a common pattern of early post-natal morphological maturation in which a progressive rearrangement from a dot-shaped to a regular and smooth fiber morphology was observed, starting from post-natal day 28 serotonergic fibers acquire the region specific morphological features present in the adult. In conclusion, we provided novel, target-specific insights on the morphology and temporal dynamics of the developing serotonergic fibers.

TIAM2S as a novel regulator for serotonin level enhances brain plasticity and locomotion behavior

“…We observed positive concordant results between the TIAM2S expression and serotonin level in this study. Previously, studies have shown the serotonergic fiber development and growth in the postnatal brain participates in enormous and progressive functions in the brain . Given that the density of serotonergic fibers is linked directly to serotonin levels, the changing of neuron number and neurite length of serotonergic neuron thus may explain the alteration of overall serotonin level found in our study.…”

“…Previously, studies have shown the serotonergic fiber development and growth in the postnatal brain participates in enormous and progressive functions in the brain. 69,70 Given that the density of serotonergic fibers is linked directly to serotonin levels, the changing of neuron number and neurite length of serotonergic neuron thus may explain the alteration of overall serotonin level found in our study. Nevertheless, the molecular mechanism underlines TIAM2S-mediated controls to alter serotonin level remain unclear and is of interest for further investigation.…”

Priming of LTP in amygdala and hippocampus by prior paired pulse facilitation paradigm in mice lacking brain serotonin

“…Therefore, in the LA the glutamate release in response to paired pulse stimulation seems to be reduced in TPH2 −/− mice. Besides differences in release probability differences in PPF in the amygdala and the hippocampus, observed in our study might be also due to differences in the density of serotonergic fibers in the CA1 region and the LA (Maddaloni et al, ).…”

“…Data points represent averaged amplitudes (mean AE SEM) normalized with respect to baseline values. Representative traces were recorded 5 min prior to tetanus (dashed lines) and 60 min after HFS/TBS stimulation (solid lines) observed in our study might be also due to differences in the density of serotonergic fibers in the CA1 region and the LA (Maddaloni et al, 2017).…”

Maternal SSRI treatment during offspring development results in long-term behavioral, cellular, and neuroimaging disruptions

“…The distinct phenotypes of prenatal-only versus postnatally-extended FLX pups may be mediated by differences in 5HT system development that occurs at these different periods. While 5HT axons reach their targets by birth, terminal field development occurs postnatally (Maddaloni et al, 2017).…”