Friday, 23rd September - h 2:00 p.m.
Seminars room, NICO
5-HT1a receptors orchestrate hippocampus development: impact on morphology, activity and behavior.
Prof. Jean-Pierre Hornung
Département des Neurosciences fondamentales
Directeur de la Plateforme de Morphologie
Faculté de Biologie et de Médecine, University of Lausanne - Suisse
Recent observations highlighted a distinct role for serotonin in regulating brain development in several compartments of the CNS. This effect is mediated by specific serotonergic receptors and can affect several stages of brain development such as cell division and migration, neuritic growth, synaptic formation and maturation.
We have investigated extensively the developmental alteration occurring in the 5HT1a-receptor mouse, in particular in the forebrain neurons with highest expression of this receptor: the CA1 pyramidal neurons of the hippocampus. Morphological analysis was performed on whole brain and organotypic culture preparation, demonstrating a specific neuritic growth exuberance regulated by the tone of the glutamatergic input from the Schaffer collaterals acting with NMDA receptors, and in particular the NR2B subunit. This increase in dendritic length correlates with increased excitatory input and enhanced LTP at low rate stimulations.
Finally, there is a correlation between these structural defect and modified behavior. Also of interest is the difference in the phenotype of males and females 5-HT1a-KO mice. The latter have essentially a spared phenotype as compared to male KO. Putative rescue mechanisms are investigated. This study unravels a series of mechanisms linking the developmental dysregulation of modulatory neurotransmitter with long term alterations in brain structure and function.
Host: Alessandro Vercelli
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