• The Serotonergic system of the mammalian brain

    Serotonergic neurons are grouped at the midline of the brainstem, forming two groups of nuclei. The rostral group projects into the forebrain while the caudal group projects into the brainstem and spinal cord. The rostral nuclei, the dorsal raphe and the median raphe bear two distinct types of axon terminals; thin varicose and large varicose terminals, respectively. The latter ones form basket terminals selectively surrounding the cell body and an initial segment of dendrites of a subpopulation of interneurons expressing calbindin. Furthermore, contrary to the small varicose fibers, large serotonergic varicosities form large synaptic contacts on subpopulations of interneurons in the upper layers of the cat cerebral cortex, representing up to half of the total number of synaptic contacts on the soma and proximal dendrites of the neurons. In organotypic co-cultures, dorsal raphe neurons re-innervate the cerebral cortex with small varicose fibers, while median raphe neurons form large varicose fibers. Both have laminar distribution similar to that observed in vivo. Thus, there are specific signals guiding the selective innervation of the cortical targets of these two serotonergic projections.

    Legend: 3D-reconstruction of the serotonergic raphe nuclei across the human brain stem. From rostral to caudal : green=central linearis n., light green=dorsal raphe n., white=median raphe n., gray=raphe magnus n., red=raphe obscurus n., white=raphe pallidus n., olive=medullary reticular formation

  • Serotonin regulates several developmental processes through a variety of receptors

    We study the role of receptor 5-HT1a using a mouse model deficient for the receptor exhibiting anxiety-like behavior (Ramboz et al., 1998). Using a combination of morphology, electrophysiology and behavioral techniques in vivo, as well as organotypic cultures of early postnatal hippocampal slices, we identified a specific exuberance of the dendritic arborization in the proximal segments of the apical dendrites of CA1 pyramidal neurons, correlating with enhanced excitability of the afferent Schaffer collateral pathway, a mechanism involving this glutamatergic synapse and its NR2B receptor. The phenotype is prominent in males, explained by a compensatory effect of activation of the estrogen receptor GPR-1 in females. In organotypic hippocampal cultures, selective activation of the 5-HT1a, NR2B and GPR-1 receptors regulates similarly the growth of the proximal apical dendrites of the neurons, suggesting cell autonomous mechanisms regulating dendritic growth. Current projects include rescue experiments by in utero targeting of the 5-HT1a receptor gene in CA1 pyramidal neurons of knock-out mice, to demonstrate the receptor’s contribution to the regulation of dendritic growth and other mutated genes affecting one of the two second messenger pathways of this G-coupled receptor. Use of cell specific depletion of the 5-HT1a gene will outline the contribution of the presynaptic or postsynaptic 5-HT1a receptor populations. There is also an indirect impact of the altered circuitry in the CA1 region on PV expression in a subpopulation of interneurons. Early gonadectomy of 5-HT1a-KO females will confirm the contribution of estrogen to the gender phenotype difference.

    Legend: GFP-expressing CA1 pyramidal neuron in the mouse hippocampus in a slice (300 mm-thick) imaged using a confocal microscope, with the emphasis on the apical dendrite arborization crossing the stratum radiatum and stratum lacunosum-moleculare