Morphometric studies of the aged hippocampus: I. Volumetric analysis in behaviorally characterized rats

Abstract

The present investigation examined the structural integrity of the aged hippocampus by using computer-aided morphometry to quantify the volume of principal hippocampal circuits in young, mature adult, and aged Long-Evans rats. A key feature of the experimental design was that the status of hippocampal-dependent learning and memory was documented prior to histologic evaluation. The following regions, which were visualized by using Timm staining, were included in the analysis: 1) outer portions of the dentate gyrus molecular layer (OML) innervated by the lateral entorhinal cortex, 2) middle portions of the molecular layer (MML) that receive input from the medial entorhinal cortex, 3) the commissural/associational zone (IML) immediately adjacent to the granule cell layer, and 4) the hilus and mossy fiber projection to the CA3 pyramidal cell field (MF). To identify morphometric changes that emerge during the same segment of the life span as age-related learning impairment, analysis of the volumetric results focused on comparisons between the mature adult group and the aged group. Among the individual regions that were analyzed, age-related decreases in total volume were restricted to the MML. This effect, however, occurred against a background of other, subtle changes that, together, reflected substantial reorganization in the normal balance of hippocampal circuitry. Age-related decreases in the proportion of the molecular layer (ML) that comprises the MML were accompanied by a corresponding increase in relative IML volume. The ratio between the volumes of the MML and the MF also displayed significant age-related decline. Overall, aging affected septal levels of the hippocampus disproportionately, and, with the exception of MML/MF volume ratio, the temporal hippocampus was spared. Finally, the status of spatial learning among the aged animals correlated selectively with decreases in the MML/ML and MML/MF ratios. These results demonstrate that the effects of aging are regionally selective and circuit specific, and they suggest that connectional reorganization may contribute to age-related decline in the computational functions of the hippocampus.

Effect of age on kainate-induced seizure severity and cell death

“…In particular, Darbin et al (2004) found an age-related reduction in fast frequencies in EEG recordings and behavioral characteristics elicited during kainate treatment in aged Fischer 344 rats, suggestive of a change in seizure network activity. Alterations in seizure network activity could result from age-related alterations in synaptic connectivity (Barnes and McNaughton, 1980;Rapp et al, 1999;Smith et al, 2000), electronic coupling (Barnes et al, 1987), receptor and channel properties (Pitler and Landfield, 1990;Gutiérrez et al, 1996), or the number and type of neurons (Shetty and Turner, 1998;Cadiacio et al, 2003;Stanley and Shetty, 2004).…”

Theta-Frequency Synaptic Potentiation in CA1In VitroDistinguishes Cognitively Impaired from Unimpaired Aged Fischer 344 Rats

“…Remarkably, lesions restricted to the dorsal hippocampus or the CA1 cell field have been shown to disrupt spatial learning in rats (Davis et al, 1986;Moser et al, 1995). However, age-related spatial learning deficits in rats do not arise from hippocampal neuron loss (Rapp and Gallagher, 1996), implicating more subtle changes in synaptic structure or function (Rapp et al, 1999;Smith et al, 2000). In line with this thinking, impaired hippocampal synaptic plasticity, specifically long-term potentiation (LTP), has been prominently cast as a key factor in age-related cognitive decline (Foster, 1999).…”

Effect of Vitamin E on Blood-Brain Barrier Permeability in Aged Rats with PTZ-Induced Convulsions

“…As was shown, these systems regulate in vivo the epileptiform activity and significantly influence the relapse severity, sensitivity, and prevalence [30,31]. Considerable modifications of synaptic connections, electrotonic coupling, features of receptors and channels, numbers and functions of specific-type neurons within neuronal networks develop due to aging [32][33][34][35][36][37]. Besides this, it was reported that age-dependent alterations also develop in the sodium/potassium equilibrium and extracellular volume, and these alterations noticeably affect neuronal synchronization and excitability [38][39][40][41].…”