Injections of leupeptin (a thiol proteinase inhibitor) or chloroquine (a general lysosomal enzyme inhibitor) into the brains of young rats induced the formation of lysosome-associated granular aggregates (dense bodies) which closely resembled the ceroid-lipofuscin that accumulates in certain disease states and during aging. The dense material increased in a dose- and time-dependent fashion and was differentially distributed across brain regions and cell types. These observations provide clues to the origins of ceroid-lipofuscin and suggest means for studying the consequences of its accumulation.

Astrocytes have been suggested to play several roles in the complex control of brain microenvironment. However, they have been generally considered to constitute a homogeneous population of cells. Here we show that at least three electrophysiologically distinct types of astrocytes can be found in the mature hippocampus. These subpopulations of glia were characterized by expression of different ion currents. In astrocytes exposed to elevated K ϩ , Cs ϩ prevented influx of K ϩ only in cells with inwardly rectifying currents (I IR ). The topographic distribution of glia with Cs ϩ -sensitive inward rectifying currents (involved in K ϩ buffering) was nonuniform. Cs ϩ -sensitive astrocytes were predominantly found in CA3 radiatum, whereas most CA1 astrocytes were Cs ϩ -insensitive. Functional significance of the spatial segregation of glial cells with inward rectification was addressed in slices that were bathed in Cs ϩ -containing media. Under these conditions, neuronal stimulation induced spontaneous epileptiform activity, which first appeared in CA3 and was then synaptically propagated to CA1. Intracellular labeling of astrocytes with biocytin revealed that CA1 astrocytes are characterized by a high degree of cell-to-cell coupling; in contrast, cell labeling in CA3 revealed smaller groups and occasionally individual cells. Three individual biocytin-labeled cells had electrophysiological properties indistinguishable from Cs ϩ -sensitive astrocytes but had morphology typical of oligodendroglia. These results provide evidence for a role of K ϩ uptake via I IR into astrocytes. The segregated expression of potassium channels in a subpopulation of astrocytes suggests that functionally specialized cell types are involved in K ϩ homeostasis.

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