Dependence of parvalbumin expression on Purkinje cell input in the deep cerebellar nuclei.
A complete loss of Purkinje cell (PC) input leads to an increase in expression of the calcium-binding protein parvalbumin (Parv) in neurons of the deep cerebellar nuclei (DCN) of PC degeneration (pcd) mutants. To verify this apparent dependence of Parv expression on PC input in the DCN, the patterns of expression in five other cerebellar mutants (weaver, staggerer, leaner, nervous, and lurcher) with differing grades and chronologies of PC loss were compared. Degree and time course of PC loss and the subsequent denervation of DCN neurons were monitored by using Calbindin D-28k (Calb) immunocytochemistry. Similar to pcd mice, somatal Parv in lurcher mutants increased massively throughout the cerebellar nuclei. In nervous and leaner mutants, somatal Parv was restricted to almost completely denervated nuclear areas, whereas areas with appreciable remnants of PC input were spared. The first appearance of Parv+ somata was closely correlated with the time course of PC degeneration--postnatal day 19 in lurcher mutants and postnatal day 23 in nervous mutants. In staggerer mice, neurons immunopositive for Parv as well as for Calb were present in outer DCN areas, likely representing ectopic PCs rather than DCN neurons. No Parv+ DCN somata were found in weaver mutants at any time. In conclusion, increased expression of somatal Parv in DCN neurons is not restricted to the specific histopathology in pcd mutants but is a common mechanism that is dependent on the topography and severeness of PC-input loss. The functional significance of the Parv increase and its possible contribution to the degree of motor disability among the different mutants are discussed.
Bäurle
J
J
Department of Physiology, Universitätsklinikum Benjamin Franklin, Fachbereich Humanmedizin, Freie Universität Berlin, Germany. baeurle@zedat.fu-berlin.de
Hoshi
M
M
Grüsser-Cornehls
U
U
D000818:Animals; D002452:Cell Count; D002529:Cerebellar Nuclei / Q000473:pathology*; D005260:Female; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants / Q000502:physiology*; D009410:Nerve Degeneration / Q000473:pathology; D009434:Neural Pathways; D009473:Neuronal Plasticity / Q000502:physiology; D010320:Parvalbumins / Q000032:analysis / Q000096:biosynthesis*; D011689:Purkinje Cells / Q000737:chemistry* / Q000473:pathology
D010320:Parvalbumins