Tesis doctoral de Bupesh Munisamy
Summary dysfunctions in emotional control and social behavior are behind several human neuropsychiatric disorders, some of which are associated to an alteration of amygdalar development. The control of emotions and social behavior is particularly associated to the so-called extended amygdala, which is a cell corridor of the basal telencephalon extending from the centromedial amygdala to the bed nucleus of the stria terminalis (bst), that constitutes the major output station to effector centers of the hypothalamus and brainstem. However, many aspects of the development of the extended amygdala remain elusive, including the embryonic origin of its different neuron subpopulations. The aim of this thesis has been to investigate the origin of the neurons of the extended amygdala in mouse embryos (e13.5-e16.5) by using in vitro migration assays. The fate mapping results were combined with immunofluorescence for analyzing the phenotype of the neurons that migrated to the amygdala from distinct origins, and were compared with data from immunohistochemistry (to label distinct neuropeptides, proteins or enzymes) and in situ hibridization (to detect the mrna expression of different transcription factors and other proteins) which helped in the delineation of forebrain embryonic domains and extended amygdala subdivisions. In particular, this thesis deals with studing the embryonic origin of the neurons of the two major subdivisions (or sub-corridors) of the extended amygdala, the medial extended amygdala (chapter 2) and the central extended amygdala (chapter 3). regarding the medial extended amygdala (chapter 2), this thesis provides experimental evidence for a multiple embryonic origin of its principal neurons, including those of the medial amygdala and medial bst. In particular, this study provides novel evidence indicating that a major part of the neurons of the medial amygdala and medial bst derives from the caudoventral part of the medial ganglionic eminence (mgecv, previously called or included as part of the anterior peduncular area), forming a cell subcorridor with similar molecular features (expression of the transcription factor lhx6 and the protein calbindin). Comparison to other data indicates that neurons along this mgecv-related cell subcorridor are interconnected and project to the same hypothalamic targets, which are involved in reproductive behavior. This thesis also provides novel experimental evidence indicating that the ventral pallium produces some neurons for the medial amygdala, which appear to express the transcription factor lhx9. The results also confirm that some neurons of the medial extended amygdala originate in the preoptic area (our results indicate that these cells specifically originate in its commissural subdivision or poc and correlate to expression of the signaling protein sonic hedgehog) and the supraopto-paraventricular domain of the hypothalamus (or spv, which derived neurons express the transcription factors lhx5 and otp). Similarly to the neurons derived from mgecv, it is possible that neurons of the medial extended amygdala derived from other embryonic domains also form distinct cell subcorridors related to specific functions. regarding the central extended amygdala (chapter 3), the results of this thesis show that its major components, including central amygdala and lateral bed nucleus of the stria terminalis (bst), are mosaics formed by different proportions of dorsal lateral ganglionic eminence (lge)-, ventral lge- and medial ganglionic eminence (mge)-derived neurons. Dorsal lge-derived neurons express the transcription factor pax6, and primarily populate lateral parts of the central amygdala, but a few also reach the lateral bst. Based on correlation with pre-proenkephalin mrna and other data, many of these cells are likely enkephalinergic projection neurons. The ventral lge-derived neurons express the transcription factor islet1, and primariy populate the central and medial parts of the central amygdala, and part of the lateral bst. Correlation with other studies suggests that these cells represent projection neurons expressing corticotropin-releasing factor. The mge produces the majority of neurons of lateral bst, but its caudoventral subdivision (mgecv) also produces an important subpopulation of projection neurons containing somatostatin for medial aspects of the central amygdala. Thus, distinct principal neurons originate in different embryonic domains, but the same domains contribute neurons to most subdivisions of the central extended amygdala, which may explain the similarity in neurochemistry and connections along the corridor. The results, together with other published data, also suggest the existence of at least three subcorridors within the central extended amygdala, each related to a different embryonic origin and involved in the control of a different aspect of fear responses and anxiety. in conclusion, this study provides important data that clarify relevant aspects on the development and adult organization of the extended amygdala, and helps to set up the foundations for a better understanding of neural control of emotions and social behavior in normal and abnormal conditions. url : http://hdl.Handle.Net/10803/52095
Datos académicos de la tesis doctoral «The extend amygdala: embryonic origin and genetic regulation of its development«
- Título de la tesis: The extend amygdala: embryonic origin and genetic regulation of its development
- Autor: Bupesh Munisamy
- Universidad: Lleida
- Fecha de lectura de la tesis: 28/10/2011
Dirección y tribunal
- Director de la tesis
- Loreta Medina Hernandez
- Tribunal
- Presidente del tribunal: Luis Puelles lopez
- nerea Moreno García (vocal)
- agustin Gonzalez gallegos (vocal)
- María del pilar Aroca tejedor (vocal)
