Increased serotonergic innervation of lumbosacral motoneurons of rolling mouse Nagoya in correlation with abnormal hindlimb extension.
Rolling Mouse Nagoya (RMN) carries a mutation in a gene encoding for alpha(1A) subunit of P/Q-type Ca(2+) channel (Ca(v)2.1). In addition to ataxia, this mutant mouse exhibits abnormal hindlimb extension, which is characterized by a sustained excessive tone of hindlimb extensor muscles. This study aimed to clarify whether serotonergic (5-HTergic) innervation of the spinal motoneurons was altered in RMN in relation to the abnormal hindlimb extension. The density of 5-HT immunoreactive fibres in the ventral horn of lumbar and sacral regions of spinal cord was significantly greater in RMN than in controls. Retrograde wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) labelling combined with 5-HT immunostaining revealed that the number of 5-HT immunoreactive terminals adjoining femoris quadriceps motoneurons was about 2.5-fold greater in RMN than in controls. Furthermore, 5-HT immunostaining in the lumbar cord ventral horn was examined in three other Ca(v)2.1 mutant mice (tottering, leaner and pogo) as to whether or not they showed the abnormal hindlimb extension. Among these mutants, the increased density of 5-HT immunoreactive fibres was observed in correlation with the presence of the abnormal hindlimb extension. The results suggest an increased 5-HTergic innervation of the lumbosacral motoneurons in correlation with the abnormal hindlimb extension in RMN and other Ca(v)2.1 mutant mice. As 5-HT is known to induce the sustained membrane depolarizations without continuous excitatory synaptic inputs (plateau potentials) in spinal motoneurons, the increased 5-HTergic innervation may cause the sustained excitation of hindlimb extensor motoneurons, resulting in the abnormal hindlimb extension.
Koyanagi
Y
Y
Department of Anatomy and Developmental Neurobiology, University of Tokushima Graduate School Institute of Health Biosciences, Tokushima 770-8503, Japan.
Sawada
K
K
Sakata-Haga
H
H
Jeong
Y-G
YG
Fukui
Y
Y
D000818:Animals; D001259:Ataxia / Q000235:genetics / Q000662:veterinary; D005260:Female; D006614:Hindlimb / Q000294:innervation / Q000503:physiopathology; D006735:Horseradish Peroxidase; D007150:Immunohistochemistry / Q000662:veterinary; D008161:Lumbosacral Region / Q000294:innervation*; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants; D009046:Motor Neurons / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000294:innervation*; D012701:Serotonin / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism
D012701:Serotonin; D006735:Horseradish Peroxidase