An Analysis of Atrophy in the Medial Mammillary Nucleus Following Hippocampal and Fornix Lesions in Humans and Nonhuman Primates

Abstract

Lesions of the hippocampal formation or transections of the fornix are followed by shrinkage of the medial mammillary nucleus (MMN). We determined whether the shrinkage of this nucleus was due to loss and/or shrinkage of neurons in addition to the loss of neuropil. We examined the MMN in a patient (KB) with an infarct that led to marked atrophy of the left hippocampus and subiculum, leaving the right MMN intact. Unbiased, stereological measurement techniques were used to compare the total cell number and individual neuronal cross-sectional areas in both left and right MMN in this patient and in two control human brains. We also analyzed the MMN in four macaque monkeys that underwent experimental unilateral transections of the fornix. The volume of the MMN on the lesioned side in KB was 55% of the unlesioned side (2.8 mm3 vs 5.1 mm3); the MMN in the monkey cases were reduced to 47–58% of the volume of the nonlesioned side. Neurons in the deafferented MMN of KB and of the monkey subjects were decreased in cross-sectional area (16–20%, P < 0.0001). There was a trend toward decreased cell numbers (11–15%) on the lesioned side in all cases. We have estimated that the loss in cell number and shrinkage of remaining cells contribute negligibly to the 45% reduction in MMN volume. Therefore, the loss of neuropil (dendrites and afferent and efferent axons) appears to be the major contributor to the change in MMN volume.