Anat Cell Biol.  2010 Sep;43(3):211-217. 10.5115/acb.2010.43.3.211.

Differential regulation of Purkinje cell dendritic spines in rolling mouse Nagoya (tg(rol)/tg(rol)), P/Q type calcium channel (alpha1(A)/Ca(v)2.1) mutant

• Oda SI
• Lee KJ
• Arii T
• Imoto K
• Hyun BH
• Park IS
• Kim H
• Rhyu IJ

• KMID: 2168876
• DOI: http://doi.org/10.5115/acb.2010.43.3.211

Abstract

Voltage dependent calcium channels (VDCC) participate in regulation of neuronal Ca2+. The Rolling mouse Nagoya (Cacna1a(tg-rol) ) is a spontaneous P/Q type VDCC mutant, which has been suggested as an animal model for some human neurological diseases such as autosomal dominant cerebellar ataxia (SCA6), familial hemiplegic migraine and episodic ataxia type-2. Morphology of Purkinje cell (PC) dendritic spine is suggested to be regulated by signal molecules such as Ca2+ and by interactions with afferent inputs. The amplitude of excitatory postsynaptic current was decreased in parallel fiber (PF) to PC synapses, whereas apparently increased in climbing fiber (CF) to PC synapses in rolling mice Nagoya. We have studied synaptic morphology changes in cerebella of this mutant strain. We previously found altered synapses between PF varicosity and PC dendritic spines. To study dendritic spine plasticity of PC in the condition of insufficient P/Q type VDCC function, we used high voltage electron microscopy (HVEM). We measured the density and length of PC dendritic spines at tertiary braches. We observed statistically a significant decrease in spine density as well as shorter spine length in rolling mice compared to wild type mice at tertiary dendritic braches. In proximal PC dendrites, however, there were more numerous dendritic spines in rolling mice Nagoya. The differential regulation of rolling PC spines at tertiary and proximal dendrites in rolling mice Nagoya suggests that two major excitatory afferent systems may be regulated reciprocally in the cerebellum of rolling mouse Nagoya.

Keyword

Ataxia; Dendritic spine; High voltage electron microscope; Purkinje cell; Voltage dependent calcium channel

MeSH Terms

Animals
Ataxia
Calcium
Calcium Channels
Cerebellar Ataxia
Cerebellum
Dendrites
Dendritic Spines
Excitatory Postsynaptic Potentials
Humans
Mice
Microscopy, Electron
Migraine with Aura
Models, Animal
Neurons
Plastics
Spine
Sprains and Strains
Synapses
Calcium
Calcium Channels
Plastics

Figure

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  Fig. 1 The dendritic spines at tertiary dendritic tree of a Purkinje cell. Decreased density and length of spines are observed in rolling mouse Nagoya (B) compared to wild type mouse (A). Some spines of rolling dendritic tree projected to irregular direction and intermingled adjacent spines (C) (Scale bar: 5 µm).

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  Fig. 2 Quantitative analyses of the dendritic spines with NIH image. The density (A) and length (B) of spines have been decreased significantly in rolling mice compared to wild type (Student t-test, P<0.05).

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  Fig. 3 Ectopic spines in proximal dendrites of rolling mouse Nagoya. High voltage electron microscope (HVEM) photomicrographs of wild type (A) and rolling (B) Purkinje cells. Numerous spines from proximal dendrtie of rolling mouse Purkinje cells are observed in both HVEM and semithin section (B, C). Spines (black or white stars) from proximal dendrite of rolling Purkinje cell make synapses with climbing fiber (Arrow, D). (Scale bar=10 µm in A, B and C; 1 µm in D).

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  Fig. 4 Parallel fiber varicosities images taken by HVEM (×8,000). Each of the varicosities was the largest varicosity observed in rolling (B) and wild type mice (A) under the same magnification observation. The varicosity of rolling was large and had multiple pale spots, considered synaptic points (Scale bar: 5 µm).

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