Visuospatial learning impairment following lesion of the cholinergic projection to the hippocampus

Ibotenic acid lesions of the vertical limb of the diagonal band of Broca (VDB) in marmosets produced significant depletions in choline acetyltransferase (ChAT) activity and a decrease in acetylcholinesterase (AChE) staining in the hippocampal formation and entorhinal cortex (to which the cholinergic neurones of the VDB project) but not in the neocortex or amygdala. Marmosets with VDB lesions were impaired on acquisition (but not retention) of repeated trial visuospatial tasks. This impairment was ameliorated by pretreatment with the cholinergic agonist pilocarpine indicating (a) that the learning impairment was a consequence of damage to the cholinergic system and (b) that the cholinergic projections exert a modulatory or enabling function on the target areas which can be substituted by a non-impulse-dependent drug action. Unlike marmosets with lesions of the basal nucleus of Meynert (NBM), VDB-lesioned animals were not impaired on learning repeated trial object discrimination and showed no change in general behaviour although they did become hypothermic and mesomorphic. These results are consistent with the suggestion that the hippocampus (perhaps in conjunction with the entorhinal cortex) is concerned primarily with memory for responses but not memory for reward and that lesions of the cholinergic system produce impairments equivalent to the effects of ablation of the terminal areas.