To lesion the
cholinergic input to the hippocampus, rats received
injections of
192 IgG-saporin into the medial septum/vertical limb of the diagonal band (MS/VDB). The lesions produced near-total loss of
choline acetyltransferase (ChAT)-positive neurons in the MS/VDB. The loss was accompanied, however, by only partial decreases (to 40% of control levels) in
acetylcholine (ACh) release in the hippocampus. Moreover, ACh release in the hippocampus increased when lesioned and control rats were tested on a spontaneous alternation task, indicating that there was significant residual
cholinergic function in the hippocampus. The lesions were sufficient to impair spontaneous alternation scores. However, this impairment could be reversed by either systemic or intra-hippocampal
injections of the indirect
cholinergic agonist,
physostigmine, providing additional evidence of residual and effective
cholinergic functions in the hippocampus of lesioned rats. Moreover, systemic
injections of
physostigmine at doses that produced mild
tremors in control rats led to more severe
tremors in the lesioned rats, suggesting upregulation of
cholinergic mechanisms after
saporin lesions, likely in brain areas other than the hippocampus. Thus, these findings provide evidence for decreases in
cholinergic input to the hippocampus accompanied by deficits on a spontaneous alternation tasks. The findings also provide evidence for considerable residual
cholinergic input to the hippocampus after
saporin lesions of the MS/VDB. Together, the results suggest that
192 IgG-saporin lesions of the MS/VDB, using methods often employed, do not fully remove septohippocampal
cholinergic input to the hippocampus but are nonetheless sufficient to produce impairments on a task impaired by hippocampal lesions.