Thesis defense Stephanie Miceli (Donders thesis series 264)

7 February 2017

Promotors: prof. dr. H. van Bokhoven, copromotors: dr. D. Schubert, dr. J.Homberg

Modulation of Barrel Cortex Microcircuitry by Serotonin

The present thesis work made use of the clear-cut cellular topology of the “normally” developed rat barrel system as a model. Understanding the detailed structure and function of the cortical microcircuits which underlie normal somatosensory processing help us define the basics for evaluating alterations which underlie disease (Courchesne et al. 2007). It is still not clear how alterations in the matrix of connections that form a cortical column can help us explain changes in sensory processing. The particular topological organisation of the primary somatosensory therefore represents a distinct model structure to attempt to investigate such phenomena. As proper development of cognitive constructs depends on accurate sensory integration, changes in the way somatosensory information is integrated can therefore be linked to neurodevelopmental disease. Here, within Chapters II-VI, I undertake a detailed analysis of some of the morphological and functional properties of neurons within the different layers of cortical column in healthy, wildtype rats (Sert+/+) and compare these same features to those of the Sert-/- rat, having been exposed to elevated 5-HT levels during critical periods of its development. Serotonin not only serves as a tool to evaluate its neuromodulatory effect on activity but also serves a “bench to bedside” purpose in evaluating the consequences of exposing the developing brain to elevated levels of 5-HT, which could translate to being exposed to SSRIs which alter brain 5-HT homeostasis during critical periods of neural development.