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Fornix transection in the marmoset produces a specific pattern of cognitive deficits, notably a lack of ability to recall visuospatial tasks learnt preoperatively, and a deficit in acquiring new visuospatial tasks following transection. Previous work has shown that this learning impairment can be ameliorated by cholinergic agonists, suggesting that it occurs as a consequence of destroying the cholinergic projection from the vertical limb of the diagonal band to the hippocampus which runs through the fornix. We have now shown that this deficit in new learning can be significantly alleviated by the 5-HT1A antagonist, WAY 100635. This result supports the suggestion that 5-HT1A projections are inhibitory on the same target cells for which cholinergic projections are excitatory, and that loss of function in the target cells caused by loss of excitatory tone can be compensated by blockade of inhibitory tone. Since cholinergic loss in the hippocampus (and neocortex) occurs in association with cognitive decline in Alzheimer's disease, these results suggest that 5-HT1A antagonists may have a role in the treatment of some of the cognitive symptoms of dementia.

Three groups of marmosets were trained to perform a series of visual discrimination tasks in a Wisconsin General Test Apparatus. Two groups then received bilateral lesions of the basal nucleus of Meynert using the excitotoxin N-methyl-D-aspartate and were found to be severely impaired on relearning a visual discrimination first learnt prior to surgery. One lesioned group then received grafts of acetylcholine-rich tissue dissected from the basal forebrain of fetal marmosets. Three months later the marmosets with lesion alone remained impaired on a number of retention and reversal tasks whereas the transplanted animals were no longer significantly impaired. Histological examination of the brains indicated that all lesioned animals had sustained substantial loss of the cholinergic neurons of the basal nucleus of Meynert (assessed by nerve growth factor receptor immunoreactivity) and that the lesion-alone animals showed marked loss of the cholinergic marker acetylcholinesterase in the dorsolateral frontal and parietal cortex. All transplanted animals had surviving graft tissue (visualized by Cresyl Violet staining, dense acetylcholinesterase staining and the presence of a limited number of nerve growth factor receptor-immunoreactive neurons) in the neocortex and 5/6 transplanted animals showed near complete restitution of acetylcholinesterase staining in frontal and parietal cortex. Examination of individual animal data showed that the animal without this restitution performed very poorly. The performance of the remaining transplanted animals was significantly better than that of the animals with lesion alone. There was a significant positive correlation between the degree of acetylcholinesterase staining and good performance on tasks sensitive to frontal lobe damage. These results demonstrate that acetylcholine-rich tissue transplanted into the neocortex of primates with damage to the cholinergic projections to the neocortex can produce substantial restitution of function provided that an appropriate level of interaction between graft and host tissue is achieved.

This is the first case of Cancer Morbidity, Mortality, and Improvement Rounds, a series of articles intended to explore the unique safety risks experienced by oncology patients through the lens of quality improvement, systems and human factors engineering, and cognitive psychology. This case highlights how multiple overlapping factors contributed to a delay in diagnosing disseminated tuberculosis in a patient with lung cancer. The discussion focuses on the ways that cognitive biases contributed to the delayed diagnosis in a patient who, with the benefit of hindsight, exhibited several signs and symptoms suggesting tuberculosis. Cancer Morbidity, Mortality, and Improvement Rounds is a series of articles intended to explore the unique safety risks experienced by oncology patients through the lens of quality improvement, systems and human factors engineering, and cognitive psychology. For purposes of clarity, each case focuses on a single theme, although, as is true for all medical incidents, there are almost always multiple, overlapping, contributing factors. The quality improvement paradigm used here, which focuses on root cause analyses and opportunities to improve care delivery systems, was previously outlined in this journal.1 [ABSTRACT FROM AUTHOR]

Fornix transection in the marmoset produces a specific pattern of cognitive deficits, notably a lack of ability to recall visuospatial tasks learnt preoperatively, and a deficit in acquiring new visuospatial tasks following transection. Previous work has shown that this learning impairment can be ameliorated by cholinergic agonists, suggesting that it occurs as a consequence of destroying the cholinergic projection from the vertical limb of the diagonal band to the hippocampus which runs through the fornix. We have now shown that this deficit in new learning can be significantly alleviated by the 5-HT[sub 1A] antagonist, WAY 100635. This result supports the suggestion that 5-HT[sub 1A] projections are inhibitory on the same target cells for which cholinergic projections are excitatory, and that loss of function in the target cells caused by loss of excitatory tone can be compensated by blockade of inhibitory tone. Since cholinergic loss in the hippocampus (and neocortex) occurs in association with cognitive decline in Alzheimer’s disease, these results suggest that 5-HT[sub 1A] antagonists may have a role in the treatment of some of the cognitive symptoms of dementia. [ABSTRACT FROM AUTHOR]