Hippocampal Interneurons (PtI)

The information below is taken from Danglot et al. review on hippocampal interneurons, and it can serve as short introduction on the subject.

Introduction

Interneuron hereby signifies a local circuit neuron (unless specified differently), which synthesizes and releases γ-aminobutyric acid (GABA). This type of cell is critical for hippocampal function since it keeps the excitatory glutamatergic component under a yin-yan balance. Accordingly, if the GABA-ergic component is reduced, epileptiform activity develops in the hippocampus, whereas enhancing the GABA-ergic tone impairs hippocampal function. Various types of interneurons are characterized from their axonal projection pattern/target, for example oriens-lacunosum-moleculare cells target the distal apical dendrites of principal cells in the stratum lacunosum-moleculare.

Hippocampal Neurogenesis

Pyramids and other cells

Pioneer work by Bayer and Altman in the rat and of Soriano et al in mice, back in the late 70s and 80s, gave insight in the neurogenetic events taking place in the putative hippocampus. It was recognized that the hippocampal neuroepithelium consists of three distinct components, each  giving birth to different neuronal types. Accordingly, the Ammonic neuroepithelium, gives rise to the pyramidal cells and large neurons in the stratum oriens and radiatum, the Dentate neuroepithelium generates granule cells and stratum moleculare large neurons. Lastly, the Fimbrial glioepithelium generates the fimbria glial cells. There is a specific timeline in the generation of each cell type , which differs among the hippocampal areas, as also within the same area pending on the cell type. Therefore, pyramidal cells of CA3 show a peak in neurogenesis on embryonic day 17 (E17) in the rat, whereas for CA1 pyramids peak neurogenesis is seen on E19.  In mice, CA3 pyramids are generated between E14-E15 and CA1 between  E15-E16 (Soriano et al., 1986, 1989a,b). Generally there is a succession of steps before the pyramids are established in the pyramidal layer: one day folowing their genesis, they migrate in the intermediate plate , a temporary lamina, and the next day they migrate towards the hippocampal plate, taking around four days for CA1 pyramids to reach their lamina and even longer for CA3.Hence, in rat, the CA1 pyramidal layer is obvious around E20 and CA3 on E22. The Dentate Gyrus can be distinguished around E21 since around 85% of the granules are generated postnatally.

Interneurons

Both in rats and mice GABA-ergic interneurons are generated prenatally, around E13-E18 in rat and E11-E17 for mice. Again there are regional differences in the birth time of the interneurons even within one hippocampal area. Hence, like cortical neurons there is a inside-out gradient of interneuron settling in the pyramidal layer, early generated neurons populate the deep positions whereas younger  interneurons pass by them to occupy higher positions.  Moreover, interneurons of the stratum oriens and stratum radiatum (plexiform layers or dendritic layers) are formed before the ones of the stratum pyramidale. In contrast to most CA1 and CA3 interneurons generated between E12-E13, DG interneurons arise later, between E13-E14.

Hippocampal Interneuron Matrix  (or matrices? )

Early tracing studies by Altman and Bayer suggested that interneurons may originate from the roof of the telencephalon. There is still dichotomy as to where the GABA-ergic interneurons originate, but according to Danglot et al., a considerable number of interneurons arise from the subpallial telencephalon (ventral telencephalon) , migrate tangenially ( in contrast to cortical neurons that migrate radially) and populate the hippocampus, striatum and neocortex. The Medial  and  Caudal Ganglionic Eminences  supply the hippocampus with interneurons (MGE: supplies only CA areas and CGE: supplies both CA and DG). These GABA-ergic interneurons are positive for Dlx2 (Dlx1/2 are homeobox genes expressed in the subpallium and have a role in the induction of GABA-ergic interneuron fate). Dlx2 positive cells can be seen on E15.5 in stratum radiatum and on E16.5 in stratum oriens (Pleasure et al. 2000). Due to this early placement in the hippocampus, its has been postulated that interneurons serve as “lighthouses” for incoming pyramidal cells and hippocampal afferents.

References

Danglot, L., Triller, A. & Marty, S. The development of hippocampal interneurons in rodents. Hippocampus 16, 1032-1060 (2006).

Soriano, E., Cobas, A. & Fairen, A. Asynchronism in the neurogenesis of GABAergic and non-GABAergic neurons in the mouse hippocampus. Brain Res 395, 88-92 (1986).

Soriano, E., Cobas, A. & Fairen, A. Neurogenesis of glutamic acid decarboxylase immunoreactive cells in the hippocampus of the mouse. II: Area dentata. J Comp Neurol 281, 603-611 (1989).

Soriano, E., Cobas, A. & Fairen, A. Neurogenesis of glutamic acid decarboxylase immunoreactive cells in the hippocampus of the mouse. I: Regio superior and regio inferior. J Comp Neurol 281, 586-602 (1989).

Pleasure, S.J., et al. Cell migration from the ganglionic eminences is required for the development of hippocampal GABAergic interneurons. Neuron 28, 727-740 (2000).

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Filed under Biology, Cell Cycle, Hippocampus, Neurons, Neuroscience, The Development Series

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