Region‐specific consequences of PCD gene expression in the olfactory system

Abstract

These studies investigated the response of olfactory bulb juxtaglomerular dopamine neurons to the loss of mitral cells in 6-7-month-old Purkinje cell degeneration (PCD) mice. Previous studies in normal mice, with tyrosine hydroxylase (TH) enzyme as a marker, demonstrated that following peripheral olfactory afferent denervation the juxtaglomerular dopamine neurons exhibited a large reduction in TH activity and immunoreactivity. These intrinsic dopamine neurons also receive afferent input via dendrodendritic contacts with mitral cells. In contrast to the deficits produced by peripheral denervation, following mitral cell degeneration in homozygous recessive PCD mice, TH activity and immunoreactivity were unaltered as compared to normal heterozygous littermates. Moreover, TH activity in the substantia nigra also was unchanged, thus suggesting that the dopamine phenotype is resistant to the influences of the pcd gene. Despite the absence of a well-defined effect of the pcd gene on neurons bearing the TH phenotype, the expression of this mutation within the olfactory system is not limited to mitral cell degeneration. The current studies also demonstrate the absence of the anterior commissure, especially pars anterior, in homozygous recessive PCD mice at 6-7 months postnatal. Whether or not the loss of the anterior commissure is a primary effect or one that is secondary to mitral cell degeneration, this structural alteration provides evidence that the pcd gene exerts more widespread effects within the olfactory system that previously appreciated. The neuronal specificity of those effects remains apparent as indicated by the lack of change in TH expression.

B‐50/GAP43 Gene Expression in the Rat Olfactory System During Postnatal Development and Aging

“…In older animals (6 and 18 months of age) B-50/GAP43 a large number of cerebellar hrkinje cells in the first 4 weeks after birth. In addition, by 3 months of age 75% of the mitral cells have been lost from the olfactory bulb (Greer and Shepherd, 1982;Greer and Halasz, 1987) but the tufted cell population is unchanged (Baker and Greer, 1990). A striking difference in B-50/GAP43 mRNA expression was observed in homozygous affected mice (pcd/pcd) as compared to their phenotypically normal littermates (pcd/ +) (Fig.…”

Changes in the connections of the main olfactory bulb after mitral cell selective neurodegeneration

“…Before this age, the cellular and synaptic organization in the OB seems to be normal, but along a short time window an accelerated mitral cell loss occurs, leading to an almost complete absence of these projection neurons by P90–P120. Other OB populations do not exhibit a comparable degenerative sequence (Baker and Greer, 1990), because mitral cells are the only neuronal population in the OB expressing the mutated gene. Despite mitral cell degeneration, the odor induced patterns of 2‐deoxyglucose uptake in OB glomeruli are not altered (Greer and Shepherd, 1982), showing that olfactory receptor cells respond in a normal manner to odors in PCD mice.…”

“…Despite mitral cell degeneration, the odor induced patterns of 2‐deoxyglucose uptake in OB glomeruli are not altered (Greer and Shepherd, 1982), showing that olfactory receptor cells respond in a normal manner to odors in PCD mice. Moreover, TH activity and immunoreactivity remain intact in the PCD OB (Baker and Greer, 1990). By contrast, the tufted cells of PCD mice, primarily unaffected (Greer and Shepherd, 1982), constitute the only centripetal pathway to convey olfactory information to secondary olfactory structures.…”

Zincergic innervation from the anterior olfactory nucleus to the olfactory bulb displays plastic responses after mitral cell loss

“…This indicates that the reported increase in the AON is the result of a selective plastic reorganization in pcd mutant mice and not a consequence of anatomical differences between the control and pcd animals. Furthermore, no changes have been described in AON volume in the pcd mouse (Baker and Greer, 1990), ruling out the hypothesis that a small AON in these mice would lead to a higher density of stained somata. These data support the notion that the differences observed in pcd mice are specific.…”

“…It is well known that the anterior commissure (AC), which communicates both hemispheres, is made up by axons from the AON and piriform cortex (Haberly and Price, 1978;Luskin and Price, 1983). In pcd mutant mice, the AC degenerates postnatally but it is still unknown whether this is due to the direct effects of the mutation or whether it is a direct consequence of mitral cell degeneration (Baker andGreer, 1990, Recio et al, 2007). With the present results it cannot be stated whether the lack of contralateral zincergic projections belongs to the causes or consequences of the AC degeneration, although it must be directly related to this process since the AC is the pathway where interhemispheric AON information is shuttled.…”