Abstract
Neurogenesis occurs throughout life in the subgranular zone of the dentate gyrus, and postnatal-born granule cells migrate into the granule cell layer and extend axons to their target areas. The α7⁎nicotinic receptor has been implicated in neuronal maturation during development of the brain and is abundant in interneurons of the hippocampal formation of the adult brain. Signalling through these same receptors is believed also to promote maturation and integration of adult-born granule cells in the hippocampal formation. We therefore aimed to determine whether functional α7⁎nicotinic receptors are expressed in developing granule cells of the postnatal dentate gyrus. For these experiments we used 2–3 week-old Wistar rats, and 2–9 week old transgenic mice in which GABAergic interneurons were marked by expression of green fluorescent protein. Immunohistochemistry indicated the presence of α7⁎nicotinic receptor subunits around granule cells close around the subgranular zone which correlated with the distribution of developmental markers for immature granule cells. Whole-cell patch clamp recording showed that a proportion of granule cells responded to puffed ACh in the presence of atropine, and that these cells possessed electrophysiological properties found in immature granule cells. The nicotinic responses were potentiated by an allosteric α7⁎nicotinic receptor modulator, which were blocked by a specific α7⁎nicotinic receptor antagonist and were not affected by ionotropic glutamate or GABA receptor antagonists. These results suggest the presence of functional somato-dendritic α7⁎nicotinic receptors on immature granule cells of the postnatal dentate gyrus, consistent with studies implicating α7⁎nicotinic receptors in dendritic maturation of dentate gyrus neurons in adult brain.
Highlights
The GABAergic interneurons of the dentate gyrus (DG) are located in the subgranular zone, hilus and molecular layer and their terminals are concentrated in the granule cell and molecular layer of the DG (Halasy and Somogyi, 1993; Houser, 2007)
Using immunohistochemistry we have shown, in both rats and mice, the presence of α7 nAChR subunits around granule cells close to the germinal layer in the subgranular zone
These findings were confirmed with α-bungarotoxin labelling. This immunohistochemical labelling corresponds with the distribution of developmental markers for immature granule cells such as weak nuclear label for NeuN and presence of doublecortin
Summary
The dentate gyrus (DG) of the hippocampal formation, a region important for spatial and episodic memory (Lisman, 1999; Burgess et al, 2002), is a well-established site of continual neurogenesis in the mammalian brain (Altman, 1962; Altman and Das, 1965; Kaplan and Hinds, 1977; Seki and Arai, 1995; Gage, 2000; Cameron and McKay, 2001), where the processes of ontogenetic developmental neurogenesis and adult neurogenesis are considered to overlap (Amrein et al, 2011). Neurogenesis continues to occur throughout life in the subgranular zone, and in the postnatal brain the newly formed neurons accumulate in the inner third of the granular layer where they differentiate and become fully integrated into the adult circuitry (Gould et al, 1999; Hastings and Gould, 1999; Wang et al, 2000; van Praag et al, 2002; Schmidt-Hieber et al, 2004; Doetsch and Hen, 2005). The most common nAChR subtypes expressed in the hippocampal formation are those based on α7 and α4β2 subunits (Deneris et al, 1988; Wada et al, 1989; 1990; Seguela et al, 1993; Dominguez del et al, 1994) They are located postsynaptically on GABAergic interneurons (Alkondon et al, 1998; Frazier et al, 1998a,b, 2003) and presynaptically on GABAergic and glutamatergic axonal terminals (Colquhoun and Patrick, 1997). Brain research 1601 (2015) 15–30 only by immature granule cells in the dentate gyrus of Wistar rats and in GAD67-GFP mice
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