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Table of contents
INTRODUCTION
1.0 Development of emotional neural circuits
1,1 Critical periods in development
1.2 Critical periods in Limbic system development
2.0 Developmental role of Serotonin (5-HT)
2.1 Development of central 5-HT systems
2.2 The serotonin transporter: cellular target of SSRIs during development
3.0 5-HT receptors
4.0 5-HT regulated emotional and cognitive behaviours
4.1 Human association to depression phenotypes
4.2 Animal model-based association to depression phenotypes
4.3 5-HT regulation of PFC circuits
5 The 5-HT7 Receptor
5.1 Gene structure and alternative splicing
5.2 Intracellular signaling of 5-HT7
5.3 Tissue localization of the 5-HTR7 in the brain
5.4 Effect of 5-HT7 signalling on neuronal morphology and functions
5.5 Effects of 5-HT7 on other biological processes
CHAPTER I: Early life stress impairs postnatal oligodendendrogenesis and adult behavior through activity dependent mechanisms
CHAPTER II: SSRIs target prefrontal to raphe circuits during development modulating synaptic connectivity and emotional behavior
CHAPTER III: Serotonin and emotional behaviours: developmental role of the 5-HT7 receptor Materials and Methods
Animals
Brain tissue processing
Western Blot
Cell Cultures
RT-qPCRs
Drug Administration (5-HT7 receptor agonist and antagonist)
Viral injections in the PFC
Array tomography
Behavioural studies
Statistical analyses
RESULTS
The 5-HT7 receptor (Htr7) is expressed in the PFC during early postnatal development
Pharmacological blockade of 5-HT7 receptor during the postnatal periods interacts with developmental fluoxetine effects.
Emotional phenotype of the Htr7-KO mice; effects of PN-FLX in Htr7-/- and Htr7+/- mice
Overexpressing Htr7 in the developing PFC causes anxiety- and depressive-like behaviours in adulthood
Activation of PFC 5-HTR7 regulates PFC-DRN circuitry
DISCUSSION
Localization of Htr7 receptor in the mouse PFC during development
Pharmacological manipulation of 5-HT7 during development alleviates anxiety- and depressive-like behaviours caused by postnatal SSRI administration
Anatomical effects of 5-HT7 receptor stimulation
Future perspectives
REFERENCES
