SELECTIVE IMMUNOLESIONS OF HIPPOCAMPAL CHOLINERGIC INPUT FAIL TO IMPAIR SPATIAL WORKING-MEMORY

The septo-hippocampal cholinergic pathway has traditionally been thoug ht of as essential for spatial memory. Recent studies have demonstrate d intact spatial learning following removal of this pathway with an im munotoxin selective for cholinergic neurons. In the present experiment , rats with selective removal of hippocampal cholinergic input were te sted in a delayed nonmatching-to-position task in a water version of t he radial arm maze. This allowed us to increase and parametrically Var y the memory load compared with the standard Morris water maze (by var ying the delay between the initial four choices and the final four cho ices) to determine ii this would reveal a deficit in rats with lesions of septo-hippocampal cholinergic projections. Male Long-Evans rats we re given injections of 192 IgG-saporin, a selective immunotoxin for ch olinergic neurons, into the medial septum/vertical limb of the diagona l band (MS/VDB) to remove cholinergic projections to the hippocampus, or a control surgery. The rats were trained on the radial maze task fo llowing surgery. An escape platform was located at the end of each arm of the maze and was removed after an arm was utilized for escape. Aft er initial training, a delay was interposed between the first four tri als and the second four trials. Errors during the second four-trial co mponent were scored in two categories:retroactive (reentering an arm c hosen before the delay) and proactive (reentering an arm chosen after the delay). Retroactive errors increased as delay increased (from 60 s to 6 h) but were equivalent in control and MS/VDB-lesion groups. Proa ctive errors did not vary with delay and were also unaffected by the l esion. Radioenzymatic assays for choline acetyltransferase activity in the hippocampus of lesioned rats confirmed a significant loss of chol inergic input from the MS/VDB. These results indicate that normal spat ial working memory is possible after substantial loss of septo-hippoca mpal cholinergic projections. (C) 1997 Wiley-Liss, Inc.