Decreased duration of Ca(2+)-mediated plateau potentials in striatal neurons from aged rats

Abstract

1. The influence of age on striatal neuron Ca2+ physiology was studied through an analysis of intracellularly recorded Ca(2+)-mediated plateau potentials. In vitro brain slices from young and aged rats were treated with the K+ channel blocker tetraethylammonium (30 mM) to facilitate the expression of plateau potentials. A sample of neurons was also filled with biocytin and post hoc correlations were performed between morphology and physiology. 2. Testing of sampling parameters in neurons from young rats revealed that tetrodotoxin did not affect the amplitude or duration of plateau potentials. The membrane potential induced during plateau testing and the rate of plateau potential generation, however, had to be held constant because these variables affected plateau potential duration. 3. A significant age-related decrease was found in the duration of Ca(2+)-mediated plateau potentials that could not be explained by alterations in the activation or inactivation properties of the plateau potential. Investigation into relationships between cell morphology and plateau potential duration revealed a number of correlations. Soma size and dendritic length were correlated with plateau potential duration, independent of age (hierarchical regression), and an age-related decrease in dendritic length but not in soma size was found. Spine density and plateau potential duration were also correlated, but the significance depended on the variance associated with age. These data indicate that the extent of somadendritic membrane (including spines) affects plateau potential duration in striatal neurons and that dendrite and spine loss in aged animals may contribute to age-related decreases in plateau potential duration. 4. The response to replacement of Ca2+ with Ba2+ was age dependent, with Ba2+ causing a greater increase in the duration of plateau potentials in young neurons. These data rule out an increase in Ca(2+)-mediated inactivation of Ca2+ channels as a primary cause for the shortening of plateau potentials in aged neurons. Our morphological findings suggest that dendritic regression in aged neurons may have reduced the number of Ca2+ channels participating in plateau potential generation, but other mechanisms related to changes in the type of Ca2+ channel expressed and possible differences in their inactivation kinetics may also contribute to the age-related change in plateau potential duration.

Age-related change in short-term synaptic plasticity intrinsic to excitatory striatal synapses

“…Nonetheless, we found, as have others, that aged brain slices tended to show less activity and the neurons were more fragile during recording (Cepeda et al, 1992;Dunia et al, 1996). In a previous study from our laboratory, we examined the impact of in vitro processing on cell viability, using the trypan blue exclusion method for staining dead cells, and found no age difference in the number of dead striatal cells in brain slices (Dunia et al, 1996). Some of the brain slices from this study were included in the trypan blue analysis.…”

“…Biocytin-filled neurons were reacted for horseradish peroxidase (HRP) histochemistry according to previously published procedures (Dunia et al, 1996;Horikawa and Armstrong, 1988). Cell body dimensions and total dendritic length measurements were made using the Eutectic Neuronal Tracing System attached directly to a Nikon Microscope (EUTECTIC, Tujunga, CA).…”

Glial gene expression during aging in rat striatum and in long-term responses to 6-OHDA lesions

“…Activated microglia also increase during normal aging in humans, in the absence of Alzheimer's disease or other specific neurodegenerative conditions (e.g., DiPatre and Gelman, 1997;Tompkins et al, 1997). In view of evidence for apoE and apoJ in the recycling of cholesterol and other membrane components after neural injury (Boyle et al, 1989;Poirier, 1994;Reeder et al, 1995), we suggest that the age-related increase of apoE, and possibly of apoJ, could reflect age-related increases in membrane remodeling, as implied by the 50% age-related loss of dendritic spine density in striatal interneurons (Dunia et al, 1996). For example, the decline of dopamine (D 2 ) receptors is detected by midlife (Morgan and May, 1990), concurrent with increased GFAP.…”

“…Because the two genotypes share a set of alleles from the F344 strain, the similar rate of GFAP increase with age could result from the dominance of one or more alleles from the shorter-lived F344 strain. Astrocyte age changes indicative of increased cell activities and gene activity are important because of opposite trends in many neuronal activities, e.g., agerelated decreases in dopamine receptor subtypes (Morgan and May, 1990;Zhang et al, 1995), in calciummediated plateau potentials, and in dendritic spine densities (Dunia et al, 1996). Conclusions about effects of aging on cell functions must be carefully developed for each cell type, e.g., in the liver, and other non-neural tissues many genes show marked decreases in transcription Van Remmen et al, 1994), which are opposite of the increases observed for three genes active in astrocytes.…”

“…Astrocyte activities tend to increase progressively during aging in most brain regions, as judged by fibrotic morphology (reviewed in Landfield, 1994;Scott and Mandybur, 1996) and increased expression of glial fibrillary acidic protein (GFAP) and GFAP mRNA, which reach 2-to 4-fold by the average lifespan, e.g., in most brain regions of humans and rodents (Gordon et al, 1997;Morgan et al, 1997;O'Callaghan and Miller, 1991). In striatum and hippocampus of male rats, GFAP expression increases during midlife (Nichols et al, 1993;Yoshida et al, 1996), a change that precedes neuronal dysfunctions (e.g., Dunia et al, 1996;Lanahan et al, 1997). The increases of GFAP mRNA represent increased content per cell (Major et al, 1997;Yoshida et al, 1996) and are associated with increased GFAP transcription (Krekowski et al, 1996;Yoshida et al, 1996).…”