Functional recovery of the dentate gyrus after a focal lesion is accompanied by structural reorganization in the adult rat

Abstract

The adult brain is highly plastic and tends to undergo substantial reorganization after injury to compensate for the lesion effects. It has been shown that such reorganization mainly relies on anatomical and biochemical modifications of the remaining cells which give rise to a network rewiring without reinstating the original morphology of the damaged region. However, few studies have analyzed the neurorepair potential of a neurogenic structure. Thus, the aim of this work was to analyze if the DG could restore its original morphology after a lesion and to establish if the structural reorganization is accompanied by behavioral and electrophysiological recovery. Using a subepileptogenic injection of kainic acid (KA), we induced a focal lesion in the DG and assessed in time (1) the loss and recovery of dependent and non dependent DG cognitive functions, (2) the anatomical reorganization of the DG using a stereological probe and immunohistochemical markers for different neuronal maturation stages and, (3) synaptic plasticity as assessed through the induction of in vivo long-term potentiation (LTP) in the mossy fiber pathway (CA3-DG). Our results show that a DG focal lesion with KA leads to a well delimited region of neuronal loss, disorganization of the structure, the loss of associated mnemonic functions and the impairment to elicit LTP. However, behavioral and synaptic plasticity expression occurs in a time dependent fashion and occurs along the morphological restoration of the DG. These results provide novel information on neural plasticity events associated to functional reorganization after damage.

Behavior‐associated Neuronal Activation After Kainic Acid‐induced Hippocampal Neurotoxicity is Modulated in Time

“…B,C). Remarkably, and in agreement with previous observations (Hernández‐Ortega, ; Zepeda et al, ) the DG of animals sacrificed at 30 days post lesion (dpl) shows a very limited region of cell loss (Fig. C) as compared to those sacrificed at 10dpl (Fig.…”

“…The hippocampus is a highly plastic structure, which has been extensively shown to display structural modifications after learning (Ramírez‐Amaya et al, ), damage (Ben‐Ari, ; Zepeda et al, ), and limbic seizures (Sutula and Dudek, ; Ben‐Ari, ), among other events. In this work we show that a focal lesion induced by an intrahippocampal infusion of KA changes the expression profile of synaptic‐ as well as of activity‐related proteins in a time‐dependent manner and in face of a spatial‐exploratory demand.…”

Age-Dependent Remarkable Regenerative Potential of the Dentate Gyrus Provided by Intrinsic Stem Cells

“…How the damage is sensed and the nature of factors triggering DG regeneration remains to be examined. Intriguingly, DG neurogenesis can be elicited not only in response to local signals but also in response to remote signals evidenced by a neurogenic response in the noninjured contralateral DG and even upon injury of other brain regions, such as following a traumatic brain injury or cortical stroke (Jin et al, 2001;Zepeda et al, 2013;X. Wang et al, 2016).…”

A general homeostatic principle following lesion induced dendritic remodeling

“…The biological phenomenon of denervation-induced plasticity has been receiving more and more attention [ 55 , 57 – 60 ]. It is now well-recognized that the structural reorganization of neurons can contribute to disease pathogenesis [ 61 , 62 ] as well as to functional regeneration following a partial injury [ 63 , 64 ]. Dendritic retraction and remodeling are widely seen in neurological diseases and are usually considered signs of pathology and malfunction.…”