Abstract
The development and maturation of cortical circuits relies on the coordinated actions of long and short range axonal guidance cues. In this regard, the class 3 semaphorins and their receptors have been seen to be involved in the development and maturation of the hippocampal connections. However, although the role of most of their family members have been described, very few data about the participation of Semaphorin 3E (Sema3E) and its receptor PlexinD1 during the development and maturation of the entorhino-hippocampal (EH) connection are available. In the present study, we focused on determining their roles both during development and in adulthood. We determined a relevant role for Sema3E/PlexinD1 in the layer-specific development of the EH connection. Indeed, mice lacking Sema3E/PlexinD1 signalling showed aberrant layering of entorhinal axons in the hippocampus during embryonic and perinatal stages. In addition, absence of Sema3E/PlexinD1 signalling results in further changes in postnatal and adult hippocampal formation, such as numerous misrouted ectopic mossy fibers. More relevantly, we describe how subgranular cells express PlexinD1 and how the absence of Sema3E induces a dysregulation of the proliferation of dentate gyrus progenitors leading to the presence of ectopic cells in the molecular layer. Lastly, Sema3E mutant mice displayed increased network excitability both in the dentate gyrus and the hippocampus proper.
Highlights
The hippocampal formation plays crucial roles in the consolidation of information from short- to long-term memory, as well as in spatial memory[1,2]
Considering that semaphorins have been described as being involved in cell proliferation (e.g.44,45), we focus our attention on analysing whether absence of Semaphorin 3E (Sema3E)-mediated signalling modifies cell proliferation in the adult hippocampus and putative effects on mossy fiber growth and hippocampal physiology
Our results indicate that Sema3E and PlexinD1 participate actively in the establishment of the EH connection by regulating the laminar termination of ingrowing entorhinal axons in the hippocampus
Summary
The hippocampal formation plays crucial roles in the consolidation of information from short- to long-term memory, as well as in spatial memory[1,2]. As described for other signalling mechanisms (i.e., Netrins43), Sema3E/PlexinD1 might play several roles in different cell types during development and in the adult. The absence of Sema3E/PlexinD1 signalling in postnatal and adult stages lead to changes in the cytoarchitecture of the dentate gyrus In their absence, an increased number of stem cell niches are observed in the subgranular zone and newborn granule cells are ectopically settled in the molecular layer. An increased number of stem cell niches are observed in the subgranular zone and newborn granule cells are ectopically settled in the molecular layer This disorganization strongly alters the laminar distribution and synaptic patterning of mossy fibers. These modifications correlate with the presence of altered functional properties as measured by means of multielectrode local field potential (LFP) recordings, revealing an enhanced excitability in Sema3E0/0 mice
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