title: High serotonin levels during brain development alter the structural input-output connectivity of neural networks in the rat somatosensory layer IV.
abstract: Homeostatic regulation of serotonin (5-HT) concentration is critical for "normal" topographical organization and development of thalamocortical (TC) afferent circuits. Down-regulation of the serotonin transporter (SERT) and the consequent impaired reuptake of 5-HT at the synapse, results in a reduced terminal branching of developing TC afferents within the primary somatosensory cortex (S1). Despite the presence of multiple genetic models, the effect of high extracellular 5-HT levels on the structure and function of developing intracortical neural networks is far from being understood. Here, using juvenile SERT knockout (SERT(-/-)) rats we investigated, in vitro, the effect of increased 5-HT levels on the structural organization of (i) the TC projections of the ventroposteromedial thalamic nucleus toward S1, (ii) the general barrel-field pattern, and (iii) the electrophysiological and morphological properties of the excitatory cell population in layer IV of S1 [spiny stellate (SpSt) and pyramidal cells]. Our results confirmed previous findings that high levels of 5-HT during development lead to a reduction of the topographical precision of TCA projections toward the barrel cortex. Also, the barrel pattern was altered but not abolished in SERT(-/-) rats. In layer IV, both excitatory SpSt and pyramidal cells showed a significantly reduced intracolumnar organization of their axonal projections. In addition, the layer IV SpSt cells gave rise to a prominent projection toward the infragranular layer Vb. Our findings point to a structural and functional reorganization of TCAs, as well as early stage intracortical microcircuitry, following the disruption of 5-HT reuptake during critical developmental periods. The increased projection pattern of the layer IV neurons suggests that the intracortical network changes are not limited to the main entry layer IV but may also affect the subsequent stages of the canonical circuits of the barrel cortex.
authors.affiliation: Department of Cognitive Neuroscience, Centre for Neuroscience, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Nijmegen Medical Centre Nijmegen, Netherlands.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Miceli
authors.forename: Moritz
authors.initials: M
authors.lastname: Negwer
authors.forename: Fenneke
authors.initials: F
authors.lastname: van Eijs
authors.forename: Carla
authors.initials: C
authors.lastname: Kalkhoven
authors.forename: Ilja
authors.initials: I
authors.lastname: van Lierop
authors.forename: Judith
authors.initials: J
authors.lastname: Homberg
authors.forename: Dirk
authors.initials: D
authors.lastname: Schubert
keywords: SERT; barrel cortex; columnar circuitry; morphology; pyramidal cell; serotonin; somatosensory; spiny stellate cell