Crossed unilateral lesions of temporal lobe structures and cholinergic cell bodies impair visual conditional and object discrimination learning in monkeys.

Monkeys with excitotoxic lesions of the CA1/subiculum region in the right hemisphere and with immunotoxic lesions of the cholinergic cells of the diagonal band in the left hemisphere were impaired on a visual conditional task. In this task, correct choice of one of two objects depends on which of two background fields both objects are presented against, irrespective of the spatial positions of the objects. They were not impaired on simple object or shape discrimination tasks. The pattern of impairments is the same as that seen after bilateral excitotoxic lesions of CA1/subiculum, implying that the diagonal band lesion disables the ipsilateral CA1/subiculum. It also argues that CA1/subiculum, sustained by its cholinergic input, is necessary for some forms of nonspatial conditional learning. Addition of an inferotemporal (IT) cortical ablation to the left hemisphere did not affect simple visual discrimination learning, although all the monkeys then failed to learn a new visual conditional task. This demonstrates that intact IT cortex in only one hemisphere is sufficient to sustain simple visual discrimination learning but implies that the cholinergic input and the inferotemporal cortical input to the hippocampus both contribute to visual conditional learning. The subsequent addition of an immunotoxic lesion of the basal nucleus of Meynert in the right hemisphere resulted in an additional impairment on a difficult shape discrimination. This argues that it is the cholinergic projection to the inferotemporal cortex, rather than to the rest of the cortex, which contributes to visual discrimination learning and memory.

Synergistic effects of unilateral immunolesions of the cholinergic projections from the basal forebrain and contralateral ablations of the inferotemporal cortex and hippocampus in monkeys.

Monkeys, with unilateral immunotoxic lesions of the basal nucleus of Meynert that remove cholinergic innervation of the ipsilesional neocortex, and ablations of the contralateral inferotemporal neocortex, were impaired on retention of visual discriminations learnt before surgery and on acquisition of new discriminations. This demonstrates that the cholinergic projection from the basal nucleus supports the functions of its cortical target area. Our previous studies have shown that the impairment on discrimination performance following bilateral lesions of the basal nucleus is transient and that bilateral lesions of the diagonal band of Broca, that remove cholinergic innervation of the hippocampus, are without effect on these tasks. However, the impairment resulting from bilateral lesions of the basal nucleus plus the diagonal band, or from bilateral inferotemporal cortex ablations, is severe and persistent. Bilateral inferotemporal ablations deprive the hippocampus of much of its visual input by producing a discontinuity in cortico-cortical transmission, whereas basal nucleus lesions may merely prevent the modification of visually-derived information in the inferotemporal cortex without depriving the hippocampus of visual input. In the monkeys with crossed unilateral basal nucleus plus inferotemporal cortex lesions, the addition of a diagonal band lesion to the basal nucleus lesion produced an impairment on retention of visual discriminations and sustained the acquisition impairment. This confirms the previous finding that the basal nucleus and diagonal band act synergistically in producing a severe and permanent impairment. Further addition of an excitotoxic hippocampal lesion to the hemisphere with the inferotemporal cortex ablation did not add to the learning impairment. This supports the suggestion that the inferotemporal cortex ablation has deprived the hippocampus of its visual input.Overall, these experiments demonstrate that the cholinergic projections from the basal nucleus and diagonal band participate in the learning and memory functions of the temporal lobes.

Different effects on learning ability after injection of the cholinergic immunotoxin ME20.4IgG-saporin into the diagonal band of Broca, basal nucleus of Meynert, or both in monkeys.

Immunotoxic lesions of the diagonal band of Broca (VDB) in monkeys disrupted cholinergic input to the hippocampus, producing impaired learning of visuospatial conditional discriminations but not simple visual discriminations. Immunotoxic lesions of the basal nucleus of Meynert (NBM) deprived the cortex of most of its cholinergic input, producing impaired learning of simple visual discriminations but not visuospatial conditional discriminations. Combined lesions of the NBM + VDB resulted in impaired learning of both types of task. The impairment after NBM lesions ameliorated with time but could be reinstated by a low dose of the glutamate blocking drug MK801, which, at this dose, did not impair simple visual discrimination learning in normal monkeys. The cholinergic projections from the NBM and VDB may sustain the function of the glutamatergic pyramidal cell pathways within the cortex and hippocampus, respectively.