HIPPOCAMPAL INTERNEURONS EXPRESSING GLUTAMIC-ACID DECARBOXYLASE AND CALCIUM-BINDING PROTEINS DECREASE WITH AGING IN FISCHER-344 RATS

Aging leads to alterations in the. function and plasticity of hippocam pal circuitry in addition to behavioral changes. To identify critical alterations in the substrate for inhibitory circuitry as a function of aging, we evaluated the numbers of hippocampal interneurons that mere positive for glutamic acid decarboxylase and those that expressed cal cium-binding proteins (parvalbumin, calbindin, and calretinin) in youn g adult (4-5 months old)and aged (23-25 months old) male Fischer 344 r ats. Both the overall interneuron population and specific subpopulatio ns of interneurons demonstrated a commensurate decline in numbers thro ughout the hippocampus with aging. Interneurons positive for glutamic acid decarboxylase were significantly depleted in the stratum radiatum of CA1, the strata oriens, radiatum and pyramidale of CA3, the dentat e molecular layer and the dentate hilus. Parvalbumin interneurons show ed significant reductions in the strata oriens and pyramidale of CA1, the stratum pyramidale of CA3, and the dentate hilus. The reductions i n calbindin interneurons mere more pronounced than other calcium-bindi ng protein-positive interneurons and were highly significant in the st rata oriens and radiatum of both CA1 and CA3 subfields and in the dent ate hilus. Calretinin interneurons were decreased significantly in the strata oriens and radiatum of CA3, in the dentate granule cell and mo lecular layers, and in the dentate hilus. However, the relative ratio of parvalbumin-, calbindin-, and calretinin-positive interneurons comp ared with glutamic acid decarboxylase-positive interneurons remained c onstant with aging, suggesting actual loss of interneurons expressing calcium-binding proteins with age. This loss contrasts with the report ed preservation of pyramidal neurons with aging in tile hippocampus. F unctional decreases in inhibitory drive throughout the hippocampus may occur due to this loss, particularly alterations in the processing of feed-forward information through the hippocampus. In addition, such a profound alteration In interneuron number will likely alter inhibitor y control of excitability and neuronal synchrony with behavioral state s. (C) 1998 Wiley-Liss, Inc.