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Impairment of mGluR signaling at cerebellar parallel fiber–Purkinje cell synapses in staggerer mutant mice
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Abstracts / Neuroscience Research 71S (2011) e108–e415
P3-h15 Factors determining performance of two limb coordinated movements in the sagittal plane
P3-h17 Impairment of mGluR signaling at cerebellar parallel fiber–Purkinje cell synapses in staggerer mutant mice
Kento Nakagawa 1 Kazuyuki Kanosue 3
Nobutake Hosoi , Kazuhiro Mitsumura, Hirokazu Hirai
, Tetsurou
Muraoka 2 , Yusuke
Uchida 3 ,
Dep. of Neurophysiology, Gunma Univ. Grad. Sch. of Med., Maebashi, Japan
1
Grad. Sch of Sport Science, Waseda Univ., Tokorozawa, Japan 2 College of Economics, Nihon Univ., Tokyo, Japan 3 Fac Sport Sci, Waseda Univ., Tokorozawa, Japan When humans perform rhythmic movement of two limbs in the sagittal plane, the “directional principle” appears: that is, the movement in the same direction is easier than the opposite direction. The purpose of this study is to examine the basis of this principle. In the first experiment, we tested the hypothesis that sending separate motor commands to two limbs is important. We compared the difficulty of movement in two conditions: (1) coordination of voluntary movements of ipsilateral hand and foot, and (2) coordination of voluntary movement of the hand and passive movement of the foot. Each condition composed of the “same direction” task and “opposite direction” task. In both conditions the difficulty of movement obeyed the directional principle. In the second experiment, we investigated the influence of kinesthetic afferent from the foot on the stability of the relationships between the positions of hand and foot. Subjects performed voluntary movement of hand with guidance of auditory pace signal, while ignoring the passive movement of ipsilateral foot that was moved by the experimenter in the same or opposite direction to the hand. No difference of the stability appeared depending on the direction of the foot movement. The results of the first and second experiments suggest that the directional principle is not based on sending separate motor commands to two limbs, nor interference of afferent signals from two limbs. Instead, comparing kinesthetic afferent from two limbs seems to be crucial for the stability of movements of two limbs. doi:10.1016/j.neures.2011.07.1073
P3-h16 Different effects of transcription and translation inhibition on transfer of memory trace of cerebellumdependent motor learning Nagao 1
Soichi , Takehito Shirao 2 , Toshinori Suzuki 1
Okamoto 1,2 ,
Shogo
Endo 3 ,
Tomoaki
1
Lab for Motor Learning Control, RIKEN BSI, Wako, Japan 2 Dept of Neurobiol and Behav, Gunma Univ Grad Sch of Med, Maebashi, Japan 3 Aging Regulation Res Team, TMIG, Tokyo, Japan It is generally assumed that protein synthesis is important in the memory retention, but not necessary for the memory acquisition (e.g., Squire, 1987; Squire and Kandel, 2000), however, the role of protein synthesis has been examined very little in cerebellum-dependent motor learning. Here, we examined the effects of local application of protein synthesis inhibitors, anisomycin and actinomycin D on the adaptation of horizontal optokinetic response (HOKR) eye movements. B6 mice received bilateral infusions of anisomycin, actinomycin D, which respectively block translation and transcription, or control Ringer’s solution into the cerebellar flocculus 1 h or 4 h before the training to view 15deg-0.16 Hz screen oscillation in head-fixed condition. The adaptation was induced by 1 h of massed training or by the 4 h spaced training of ×4 of 15 min training with 1 h interval. Eye movements were measured by an IR-TV camera system, and gains of HOKR (evoked eye movement vs. screen movement) were compared between the two trainings. Both the massed and spaced training induced similar amount of HOKR gain increase after Ringer’s solution infusions. The adaptation induced by massed training was not affected by anisomycin infusions. The adaptation induced by spaced training was depressed by anisomycin or actinomycin D infusions, however, a recover of adaptation was observed 24 h after anisomycin infusions, but not after actinomycin D infusions. Taken together with the results of our previous study that the memory trace adaptation is transferred from the cerebellar flocculus to vestibular nuclei within 4 h of spaced training, we suggest an important role of protein synthesis in the transfer of memory trace of adaptation. Research fund: This study was supported by a Grant-in-Aid from the Japan Society for Promotion of Science (22300112). doi:10.1016/j.neures.2011.07.1074
Staggerer mutant mice have a functional loss of a transcription factor, retinoid-related orphan receptor ␣ (ROR␣), which is abundantly expressed in Purkinje cells (PCs) of the cerebellum. In addition to the developmental study, the homozygous staggerer (sg/sg) mice that exhibit cerebellar hypoplasia and severe ataxia, can serve as a good model for the hereditary spinocerebellar ataxia, because ROR␣ interacts with ataxin1, whose polyglutamine expansion causes spinocerebellar ataxia type 1. The sg/sg cerebellum is small, PCs are not arranged in a monolayer and the dendrites are rudimentary. Moreover, it has been reported that parallel fibers (PFs) are not able to form mature functional synapses onto PCs in the sg/sg mice although some of them can form primitive synapse-like junctional structure on PCs. In contrast to the extensive morphological studies, detailed electrophysiological investigation has not been performed on sg/sg PF–PC synapses. In this study, we report that PFs can still establish functional synapses onto PCs in sg/sg mice. Compared with PF-evoked EPSCs in wild type or in the heterozygotes, success rate of the EPSC recordings in sg/sg was quite low (∼40%) and the EPSCs showed faster kinetics and slightly decreased paired pulse facilitation at short intervals. The most prominent phenotypical difference is that the sg/sg mice lack metabotropic glutamate receptor (mGluR)-mediated slow EPSCs completely. Neither PF activation nor exogenously applied mGluR agonist, DHPG could elicit the mGluR-mediated responses. Western blot analysis and immunohistochemical data in the sg/sg cerebellum revealed low-level expression of mGluR1 and TRPC3, both of which underlie the mGluR-mediated slow response in PCs. We found that mGluR-mediated retrograde suppression of PF–PC EPSCs by endocannabinoid was also deficient completely in the sg/sg mice. These results suggest that impairment of mGluR signaling is one of the major defects at PF–PC synapses in the sg/sg mutant mice. doi:10.1016/j.neures.2011.07.1075
P3-h18 The origin of high-frequency firing pattern of the cerebellar mossy fibers Taro Ishikawa 1 , Misa Shimuta 1 , Wen-Bin Li 1,2 1
Dept. Pharmacology, Jikei Univ. Sch. of Med., Tokyo, Japan 2 Dept. Pathophysiology, Hebei Medical Univ., Shijiazhuang, China
Somatosensory signals from the facial area of rodents are delivered to the cerebellum via pontocerebellar and trigeminocerebellar pathways. Projection fibers of these pathways form mossy fibers, which terminate in the granule cell layer of the cerebellar cortex. It has been previously reported that somatosensory stimulation to the whiskers and the perioral skin triggers burst firings of the mossy fibers and that the instantaneous frequency of such burst action potentials can exceed 700 Hz. It has not been known, however, which of the cerebellar afferent pathways conducts such high-frequency firings. It is possible that these two pathways may convey qualitatively different signals, given that the activity of trigeminal nuclei (TrgN) is a direct representation of sensory information while the pontine nuclei (PN) relay descending signals from the cerebral cortex. In this study, we investigated firing properties of projection neurons of PN and TrgN in acute slice preparations from rats. The input resistance was not significantly different between PN and TrgN neurons. During depolarizing pulses (500 ms), PN neurons did not fire high-frequency action potentials but showed regular firing with moderate accommodation. The maximum instantaneous frequency of individual PN cells was 223 ± 18 Hz (mean ± sem; N = 14 cells; range between 122 and 316 Hz). In contrast, TrgN neurons showed burst firing at the onset of depolarization, which had high instantaneous frequency exceeding 400 Hz in 60% of cells and 700 Hz in 20% of cells (n = 10). These results suggest that the highfrequency firings (above around 350 Hz) of cerebellar mossy fibers are direct signals from TrgN. Research fund: KAKENHI21800056, Takeda Science Foundation. doi:10.1016/j.neures.2011.07.1076
Abstracts / Neuroscience Research 71S (2011) e108–e415
P3-h15 Factors determining performance of two limb coordinated movements in the sagittal plane
P3-h17 Impairment of mGluR signaling at cerebellar parallel fiber–Purkinje cell synapses in staggerer mutant mice
Kento Nakagawa 1 Kazuyuki Kanosue 3
Nobutake Hosoi , Kazuhiro Mitsumura, Hirokazu Hirai
, Tetsurou
Muraoka 2 , Yusuke
Uchida 3 ,
Dep. of Neurophysiology, Gunma Univ. Grad. Sch. of Med., Maebashi, Japan
1
Grad. Sch of Sport Science, Waseda Univ., Tokorozawa, Japan 2 College of Economics, Nihon Univ., Tokyo, Japan 3 Fac Sport Sci, Waseda Univ., Tokorozawa, Japan When humans perform rhythmic movement of two limbs in the sagittal plane, the “directional principle” appears: that is, the movement in the same direction is easier than the opposite direction. The purpose of this study is to examine the basis of this principle. In the first experiment, we tested the hypothesis that sending separate motor commands to two limbs is important. We compared the difficulty of movement in two conditions: (1) coordination of voluntary movements of ipsilateral hand and foot, and (2) coordination of voluntary movement of the hand and passive movement of the foot. Each condition composed of the “same direction” task and “opposite direction” task. In both conditions the difficulty of movement obeyed the directional principle. In the second experiment, we investigated the influence of kinesthetic afferent from the foot on the stability of the relationships between the positions of hand and foot. Subjects performed voluntary movement of hand with guidance of auditory pace signal, while ignoring the passive movement of ipsilateral foot that was moved by the experimenter in the same or opposite direction to the hand. No difference of the stability appeared depending on the direction of the foot movement. The results of the first and second experiments suggest that the directional principle is not based on sending separate motor commands to two limbs, nor interference of afferent signals from two limbs. Instead, comparing kinesthetic afferent from two limbs seems to be crucial for the stability of movements of two limbs. doi:10.1016/j.neures.2011.07.1073
P3-h16 Different effects of transcription and translation inhibition on transfer of memory trace of cerebellumdependent motor learning Nagao 1
Soichi , Takehito Shirao 2 , Toshinori Suzuki 1
Okamoto 1,2 ,
Shogo
Endo 3 ,
Tomoaki
1
Lab for Motor Learning Control, RIKEN BSI, Wako, Japan 2 Dept of Neurobiol and Behav, Gunma Univ Grad Sch of Med, Maebashi, Japan 3 Aging Regulation Res Team, TMIG, Tokyo, Japan It is generally assumed that protein synthesis is important in the memory retention, but not necessary for the memory acquisition (e.g., Squire, 1987; Squire and Kandel, 2000), however, the role of protein synthesis has been examined very little in cerebellum-dependent motor learning. Here, we examined the effects of local application of protein synthesis inhibitors, anisomycin and actinomycin D on the adaptation of horizontal optokinetic response (HOKR) eye movements. B6 mice received bilateral infusions of anisomycin, actinomycin D, which respectively block translation and transcription, or control Ringer’s solution into the cerebellar flocculus 1 h or 4 h before the training to view 15deg-0.16 Hz screen oscillation in head-fixed condition. The adaptation was induced by 1 h of massed training or by the 4 h spaced training of ×4 of 15 min training with 1 h interval. Eye movements were measured by an IR-TV camera system, and gains of HOKR (evoked eye movement vs. screen movement) were compared between the two trainings. Both the massed and spaced training induced similar amount of HOKR gain increase after Ringer’s solution infusions. The adaptation induced by massed training was not affected by anisomycin infusions. The adaptation induced by spaced training was depressed by anisomycin or actinomycin D infusions, however, a recover of adaptation was observed 24 h after anisomycin infusions, but not after actinomycin D infusions. Taken together with the results of our previous study that the memory trace adaptation is transferred from the cerebellar flocculus to vestibular nuclei within 4 h of spaced training, we suggest an important role of protein synthesis in the transfer of memory trace of adaptation. Research fund: This study was supported by a Grant-in-Aid from the Japan Society for Promotion of Science (22300112). doi:10.1016/j.neures.2011.07.1074
Staggerer mutant mice have a functional loss of a transcription factor, retinoid-related orphan receptor ␣ (ROR␣), which is abundantly expressed in Purkinje cells (PCs) of the cerebellum. In addition to the developmental study, the homozygous staggerer (sg/sg) mice that exhibit cerebellar hypoplasia and severe ataxia, can serve as a good model for the hereditary spinocerebellar ataxia, because ROR␣ interacts with ataxin1, whose polyglutamine expansion causes spinocerebellar ataxia type 1. The sg/sg cerebellum is small, PCs are not arranged in a monolayer and the dendrites are rudimentary. Moreover, it has been reported that parallel fibers (PFs) are not able to form mature functional synapses onto PCs in the sg/sg mice although some of them can form primitive synapse-like junctional structure on PCs. In contrast to the extensive morphological studies, detailed electrophysiological investigation has not been performed on sg/sg PF–PC synapses. In this study, we report that PFs can still establish functional synapses onto PCs in sg/sg mice. Compared with PF-evoked EPSCs in wild type or in the heterozygotes, success rate of the EPSC recordings in sg/sg was quite low (∼40%) and the EPSCs showed faster kinetics and slightly decreased paired pulse facilitation at short intervals. The most prominent phenotypical difference is that the sg/sg mice lack metabotropic glutamate receptor (mGluR)-mediated slow EPSCs completely. Neither PF activation nor exogenously applied mGluR agonist, DHPG could elicit the mGluR-mediated responses. Western blot analysis and immunohistochemical data in the sg/sg cerebellum revealed low-level expression of mGluR1 and TRPC3, both of which underlie the mGluR-mediated slow response in PCs. We found that mGluR-mediated retrograde suppression of PF–PC EPSCs by endocannabinoid was also deficient completely in the sg/sg mice. These results suggest that impairment of mGluR signaling is one of the major defects at PF–PC synapses in the sg/sg mutant mice. doi:10.1016/j.neures.2011.07.1075
P3-h18 The origin of high-frequency firing pattern of the cerebellar mossy fibers Taro Ishikawa 1 , Misa Shimuta 1 , Wen-Bin Li 1,2 1
Dept. Pharmacology, Jikei Univ. Sch. of Med., Tokyo, Japan 2 Dept. Pathophysiology, Hebei Medical Univ., Shijiazhuang, China
Somatosensory signals from the facial area of rodents are delivered to the cerebellum via pontocerebellar and trigeminocerebellar pathways. Projection fibers of these pathways form mossy fibers, which terminate in the granule cell layer of the cerebellar cortex. It has been previously reported that somatosensory stimulation to the whiskers and the perioral skin triggers burst firings of the mossy fibers and that the instantaneous frequency of such burst action potentials can exceed 700 Hz. It has not been known, however, which of the cerebellar afferent pathways conducts such high-frequency firings. It is possible that these two pathways may convey qualitatively different signals, given that the activity of trigeminal nuclei (TrgN) is a direct representation of sensory information while the pontine nuclei (PN) relay descending signals from the cerebral cortex. In this study, we investigated firing properties of projection neurons of PN and TrgN in acute slice preparations from rats. The input resistance was not significantly different between PN and TrgN neurons. During depolarizing pulses (500 ms), PN neurons did not fire high-frequency action potentials but showed regular firing with moderate accommodation. The maximum instantaneous frequency of individual PN cells was 223 ± 18 Hz (mean ± sem; N = 14 cells; range between 122 and 316 Hz). In contrast, TrgN neurons showed burst firing at the onset of depolarization, which had high instantaneous frequency exceeding 400 Hz in 60% of cells and 700 Hz in 20% of cells (n = 10). These results suggest that the highfrequency firings (above around 350 Hz) of cerebellar mossy fibers are direct signals from TrgN. Research fund: KAKENHI21800056, Takeda Science Foundation. doi:10.1016/j.neures.2011.07.1076