Dendritic morphology, synaptic transmission, and activity of mature granule cells born following pilocarpine-induced status epilepticus in the rat.

Fei Gao,J Victor Nadler,Xueying Song,Aijun Hao,Dexiao Zhu,Xiaochen Wang,Ren-Zhi Zhan

doi:10.3389/fncel.2015.00384

Abstract

To understand the potential role of enhanced hippocampal neurogenesis after pilocarpine-induced status epilepticus (SE) in the development of epilepsy, we quantitatively analyzed the geometry of apical dendrites, synaptic transmission, and activation levels of normotopically distributed mature newborn granule cells in the rat. SE in male Sprague-Dawley rats (between 6 and 7 weeks old) lasting for more than 2 h was induced by an intraperitoneal injection of pilocarpine. The complexity, spine density, miniature post-synaptic currents, and activity-regulated cytoskeleton-associated protein (Arc) expression of granule cells born 5 days after SE were studied between 10 and 17 weeks after CAG-GFP retroviral vector-mediated labeling. Mature granule cells born after SE had dendritic complexity similar to that of granule cells born naturally, but with denser mushroom-like spines in dendritic segments located in the outer molecular layer. Miniature inhibitory post-synaptic currents (mIPSCs) were similar between the controls and rats subjected to SE; however, smaller miniature excitatory post-synaptic current (mEPSC) amplitude with a trend toward less frequent was found in mature granule cells born after SE. After maturation, granule cells born after SE did not show denser Arc expression in the resting condition or 2 h after being activated by pentylenetetrazol-induced transient seizure activity than vicinal GFP-unlabeled granule cells. Thus our results suggest that normotopic granule cells born after pilocarpine-induced SE are no more active when mature than age-matched, naturally born granule cells.

Highlights

Within days after seizure activity, especially after status epilepticus (SE), neurogenesis is enhanced in the hippocampal dentate gyrus (Parent et al, 1997; Gray and Sundstrom, 1998; Scott et al, 1998; Scharfman et al, 2000)
This study identified two significant differences between normotopic dentate granule cells born after SE or in a normal environment: in granule cells born after SE, the distal dendritic segments had a higher density of mushroom spines but the mean miniature excitatory post-synaptic current (mEPSC) amplitude was smaller
Hilar ectopic granule cells are morphologically and electrophysiologically different from normotopic granule cells; when compared to normotopic granule cells, higher percentages of hilar ectopic granule cells have a basal dendrite extending into the hilus (Ribak et al, 2000; Shapiro et al, 2005; Cameron et al, 2011), exhibit spontaneous firing and/or generate burst firing in response to depolarization (Scharfman et al, 2000; Zhan and Nadler, 2009; Althaus et al, 2015), and demonstrate unbalanced excitation and inhibition (Dashtipour et al, 2001; Zhan et al, 2010)

Summary

Introduction

Within days after seizure activity, especially after status epilepticus (SE), neurogenesis is enhanced in the hippocampal dentate gyrus (Parent et al, 1997; Gray and Sundstrom, 1998; Scott et al, 1998; Scharfman et al, 2000). Most ectopically located granule cells are in the hilus (Parent et al, 1997; Scharfman et al, 2000; Dashtipour et al, 2001), but a small portion of them are present in the molecular layer (Liang et al, 2013). Morphological, electrophysiological, and functional studies aimed at exploring the influence of normotopic newborn granule cells in the development of epilepsy have reached somewhat conflicting conclusions (Bielefeld et al, 2014). As the adult hippocampal neurogenesis plays an important role in learning, memory formation, and mood regulation (Deng et al, 2010; Samuels and Hen, 2011), illustrating the structural and functional differences between granule cells born after SE and those born naturally would be helpful in understanding the role of enhanced neurogenesis for the development of epilepsy and for the occurrence of comorbid cognitive impairment and behavioral disturbances (Chauvière et al, 2009; Cavarsan et al, 2013)

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Results

Conclusion