Rapid transneuronal degeneration and death of cortical neurons following removal of the olfactory bulb in adult rats

Abstract

Following olfactory bulb removal in young and adult rats, many neurons in the primary olfactory cortex become markedly argyrophilic in silver impregnated preparations. Although argyrophilic neurons are found scattered throughout the pyramidal and multiform cell layers, the heaviest concentration is seen in the superficial part of the pyramidal layer.Electron microscopic analysis reveals that argyrophilic neurons are undergoing rapid degeneration. The degenerative changes are similar in all affected cells, although some cells begin to disintegrate within 24 hours following bulbectomy, whereas others are just beginning to show pathological changes at three or four days. The first clear signs of cellular degeneration occur in the cytoplasm of the perikaryon and involve swelling of mitochondria and polysome disaggregation. An increase in the electron density of the cytoplasm follows and this is accompanied by the appearance of enlarged cisternae and disruption of the nuclear membrane. Degenerative changes in the nucleus usually are detected at a slightly later stage than in the cytoplasm. Nuclear changes are characterized by the proliferation of local aggregations of condensed chromatin, and the replacement of the nucleolus with large homogenous islands of electron dense material. In advanced stages of degeneration ribosomes are increased in density and become uniformly dispersed throughout the cytoplasm. Remnants of necrotic organelles are visible only at the cellular periphery, and phagocytosis of dying neurons by astrocytes and microglia follows quickly.Evidence from HRP‐studies indicates that cells in the olfactory cortex, which project directly to the bulb do not correspond to those which show fulminant necrosis following olfactory bulb removal. The majority of those which degenerate are located superficially, whereas the cells of origin of the centrifugal projection lie more deeply. Based on this dissociation, it is proposed that rapid cell death in the olfactory cortex is not caused by retrograde factors involving axotomy, but is due instead to transneuronal deafferentation that results from a sudden massive loss of input from the olfactory bulb.