MORPHOLOGIC ALTERATIONS OF CHOLINE ACETYLTRANSFERASE-POSITIVE NEURONSIN THE BASAL FOREBRAIN OF AGED BEHAVIORALLY CHARACTERIZED FISHER 344 RATS

We examined Fisher 344 female rats aged 6, 27, and 33 months old. Prio r to sacrifice and morphometric analyses of forebrain cholinergic neur ons all rats underwent behavioral characterization in a spatial learni ng task using die Morris water maze. Performance on the spatial task p ermitted subsequent grouping of the 27- and 33-month-old animals into impaired or nonimpaired groups. Importantly, the percentage of animals that displayed spatial impairments increased sharply with advancing a ge. Quantitative assessment of the size and density of choline acetylt ransferase (ChAT) - positive neurons throughout the basal forebrain re vealed a significant enlargement of forebrain cholinergic neurons with in 27-month-old nonimpaired rats compared to 6-month-old rats and 27- and 33-month-old impaired animals. This increase in size was most note d in the medial septum and nucleus of the diagonal band. Significant d ecreases in the density of ChAT-positive neurons was observed only in the nucleus of the diagonal band of 27-month-old impaired rats compare d to 6-month-old controls. Although the significance of enlarged foreb rain cholinergic neurons is unclear, we discuss the possibility that w ithin aged rodents neuronal swelling is an active event and represents an early manifestation of the aging process and may constitute a rest orative and/or compensatory event in that these rats are relatively as ymptomatic with respect to their behavioral deficits. In addition, we discuss in some detail various technical and life effect issues which may vary the outcome of investigations of aged rodents.