National Institute of Genetics NIG

Mishima, Japan

National Institute of Genetics NIG

Mishima, Japan
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Arakawa H.,University of Maryland Baltimore County | Suzuki A.,National Institute of Genetics NIG | Zhao S.,University of Maryland Baltimore County | Tsytsarev V.,University of Maryland Baltimore County | And 5 more authors.
Journal of Neuroscience | Year: 2014

NMDARs play a major role in patterning of topographic sensory maps in the brain. Genetic knock-out of the essential subunit ofNMDARs in excitatory cortical neurons prevents whisker-specific neural pattern formation in the barrel cortex. To determine the role of NMDARs en route to the cortex, we generated sensory thalamus-specific NR1 (Grin1)-null mice (ThNR1KO). A multipronged approach, using histology, electrophysiology, optical imaging, and behavioral testing revealed that, in these mice, whisker patterns develop in the trigeminal brainstem but do not develop in the somatosensory thalamus. Subsequently, there is no barrel formation in the neocortex yet a partial afferent patterning develops. Whisker stimulation evokes weak cortical activity and presynaptic neurotransmitter release probability is also affected. We found several behavioral deficits in tasks, ranging from sensorimotor to social and cognitive. Collectively, these results show that thalamic NMDARs play a critical role in the patterning of the somatosensory thalamic and cortical maps and their impairment may lead to pronounced behavioral defects. © 2014 the authors.

Takahashi A.,National Institute of Genetics NIG | Shiroishi T.,SOKENDAI | Shiroishi T.,National Institute of Genetics NIG | Koide T.,National Institute of Genetics NIG
Frontiers in Neuroscience | Year: 2014

The Japanese wild-derived mouse strain MSM/Ms (MSM) retains a wide range of traits related to behavioral wildness, including high levels of emotionality and avoidance of humans. In this study, we observed that MSM showed a markedly higher level of aggression than the standard laboratory strain C57BL/6J. Whereas almost all MSM males showed high frequencies of attack bites and pursuit in the resident-intruder test, only a few C57BL/6J males showed aggressive behaviors, with these behaviors observed at only a low frequency. Sexually mature MSM males in their home cages killed their littermates, or sometimes female pair-mates. To study the genetic and neurobiological mechanisms that underlie the escalated aggression observed in MSM mice, we analyzed reciprocal F1 crosses and five consomic strains of MSM (Chr 4, 13, 15, X and Y) against the background of C57BL/6J. We identified two chromosomes, Chr 4 and Chr 15, which were involved in the heightened aggression observed in MSM. These chromosomes had different effects on aggression: whereas MSM Chr 15 increased agitation and initiation of aggressive events, MSM Chr 4 induced a maladaptive level of aggressive behavior. Expression analysis of mRNAs of serotonin receptors, serotonin transporter and Tph2, an enzyme involved in serotonin synthesis in seven brain areas, indicated several differences among MSM, C57BL/6J, and their consomic strains. We found that Tph2 expression in the midbrain was increased in the Chr 4 consomic strain, as well as in MSM, and that there was a strong positive genetic correlation between aggressive behavior and Tph2 expression at the mRNA level. Therefore, it is possible that increased expression of the Tph2 gene is related to escalated aggression observed in MSM. © 2014 Takahashi, Shiroishi and Koide.

Takahashi A.,National Institute of Genetics NIG | Schilit A.N.,Tufts University | Kim J.,Tufts University | Debold J.F.,Tufts University | And 2 more authors.
Psychopharmacology | Year: 2012

Rationale: Pharmacological activation of GABAB receptors in the dorsal raphe nucleus (DRN) can escalate territorial aggression in male mice. Objectives: We characterized this escalated aggression in terms of its behavioral and environmental determinants. Methods: Aggressive behavior of resident male (CFW or ICR mouse) was assessed in confrontations with a group-housed intruder. Either baclofen (0.06 nmol/0.2 μl) or vehicle (saline) was microinjected into the DRN 10 min before the confrontation. We examined baclofen-heightened aggression in five situations: aggression in a neutral arena and after social instigation (experiment 1), aggression during the light phase of the cycle (experiment 2), aggression without prior fighting experience (experiment 3), aggression toward a female (experiment 4), and aggression after defeat experiences (experiment 5). In addition, we examined the body targets towards which bites are directed and the duration of aggressive bursts after baclofen treatment. Results: Regardless of the past social experience, baclofen escalated aggressive behaviors. Even in the neutral arena and after defeat experiences, where aggressive behaviors were inhibited, baclofen significantly increased aggression. Baclofen increased attack bites directed at vulnerable body areas of male intruders but not toward a female and only in the dark. Also, baclofen prolonged the duration of aggressive bursts. Conclusions: For baclofen to escalate aggression, specific stimulation (male intruder) and tonic level of serotonin (dark cycle) are required. Once aggressive behavior is triggered, intra-DRN baclofen escalates the level of aggression to abnormal levels and renders it difficult to terminate. Also, baclofen counteracts the effects of novelty or past experiences of defeat. © 2012 Springer-Verlag.

Suzuki A.,National Institute of Genetics NIG | Suzuki A.,Graduate University for Advanced Studies | Lee L.-J.,National Taiwan University | Hayashi Y.,RIKEN | And 5 more authors.
Neuroscience | Year: 2015

Cyclic AMP signaling is critical for activity-dependent refinement of neuronal circuits. Global disruption of adenylyl cyclase 1 (AC1), the major calcium/calmodulin-stimulated adenylyl cyclase in the brain, impairs formation of whisker-related discrete neural modules (the barrels) in cortical layer 4 in mice. Since AC1 is expressed both in the thalamus and the neocortex, the question of whether pre- or postsynaptic (or both) AC1 plays a role in barrel formation has emerged. Previously, we generated cortex-specific AC1 knockout (Cx-AC1KO) mice and found that these animals develop histologically normal barrels, suggesting a potentially more prominent role for thalamic AC1 in barrel formation. To determine this, we generated three new lines of mice: one in which AC1 is disrupted in nearly half of the thalamic ventrobasal nucleus cells in addition to the cortical excitatory neurons (Cx/pTh-AC1KO mouse), and another in which AC1 is disrupted in the thalamus but not in the cortex or brainstem nuclei of the somatosensory system (Th-AC1KO mouse). Cx/pTh-AC1KO mice show severe deficits in barrel formation. Th-AC1KO mice show even more severe disruption in barrel patterning. In these two lines, single thalamocortical (TC) axon labeling revealed a larger lateral extent of TC axons in layer 4 compared to controls. In the third line, all calcium-stimulated adenylyl cyclases (both AC1 and AC8) are deleted in cortical excitatory neurons. These mice have normal barrels. Taken together, these results indicate that thalamic AC1 plays a major role in patterning and refinement of the mouse TC circuitry. © 2015 IBRO.

Takahashi A.,National Institute of Genetics NIG | Takahashi A.,Graduate University for Advanced Studies | Nagayasu K.,Osaka University | Nagayasu K.,Kyoto University | And 4 more authors.
PLoS ONE | Year: 2014

Aggressive behavior is widely observed throughout the animal kingdom because of its adaptiveness for social animals. However, when aggressive behavior exceeds the species-typical level, it is no longer adaptive, so there should be a mechanism to control excessive aggression to keep it within the adaptive range. Using optogenetics, we demonstrate that activation of excitatory neurons in the medial prefrontal cortex (mPFC), but not the orbitofrontal cortex (OFC), inhibits intermale aggression in mice. At the same time, optogenetic silencing of mPFC neurons causes an escalation of aggressive behavior both quantitatively and qualitatively. Activation of the mPFC suppresses aggressive bursts and reduces the intensity of aggressive behavior, but does not change the duration of the aggressive bursts. Our findings suggest that mPFC activity has an inhibitory role in the initiation and execution, but not the termination, of aggressive behavior, and maintains such behavior within the adaptive range. © 2014 Takahashi et al.

Takahashi A.,University of Tsukuba | Takahashi A.,National Institute of Genetics NIG | Takahashi A.,Graduate University for Advanced Studies | Lee R.X.,National Institute of Genetics NIG | And 9 more authors.
Journal of Neuroscience | Year: 2015

Although the dorsal raphe nucleus (DRN) has long been linked to neural control of aggression, little is known about the regulatory influences of the DRN when an animal engages in either adaptive species-typical aggressive behavior or escalated aggression. Therefore it is important to explore which neurotransmitter inputs into theDRNdetermine the escalation of aggression in male mice. Previously,we observed that microinjection of the GABAB receptor agonist baclofen into the DRN escalates aggressive behavior in male mice. Here, we used a serotonin (5-HT) neuron-specific GABAB receptor knock-out mouse to demonstrate that baclofen acts on nonserotonergic neurons to escalate aggression. Intra-DRN baclofen administration increased glutamate release, but did not alter GABA release, within the DRN. Microinjection of L-glutamate into the DRN escalated dose-dependently attack bites toward an intruder. In vivo microdialysis showed that glutamate release increased in the DRN during an aggressive encounter, and the level of glutamate was further increased when the animal was engaged in escalated aggressive behavior after social instigation. Finally, 5-HT release was increased within theDRN and also in the medial prefrontal cortex when animals were provoked by social instigation, and during escalated aggression after social instigation, but this increase in 5-HT release was not observed when animals were engaged in species-typical aggression. In summary, glutamate input into theDRNis enhanced during escalated aggression, which causes a phasic increase of 5-HT release from theDRN5-HT neurons. © 2015 the authors.

Komiya R.,National Institute of Genetics NIG | Komiya R.,Okinawa Institute of Science and Technology | Ohyanagi H.,Plant Genetics Laboratory | Ohyanagi H.,Mitsubishi Group | And 7 more authors.
Plant Journal | Year: 2014

Small RNAs that interact with Argonaute (AGO) proteins play central roles in RNA-mediated silencing. MEIOSIS ARRESTED AT LEPTOTENE1 (MEL1), a rice AGO, has specific functions in the development of pre-meiotic germ cells and the progression of meiosis. Here, we show that MEL1, which is located mostly in the cytoplasm of germ cells, associates preferentially with 21-nucleotide phased small interfering RNAs (phasiRNAs) that bear a 5′-terminal cytosine. Most phasiRNAs are derived from 1171 intergenic clusters distributed on all rice chromosomes. From these clusters, over 700 large intergenic, non-coding RNAs (lincRNAs) that contain the consensus sequence complementary to miR2118 are transcribed specifically in inflorescences, and cleaved within the miR2118 site. Cleaved lincRNAs are processed via DICER-LIKE4 (DCL4) protein, resulting in production of phasiRNAs. This study provides the evidence that the miR2118-dependent and the DCL4-dependent pathways are both required for biogenesis of 21-nt phasiRNAs associated with germline-specific MEL1 AGO in rice, and over 700 lincRNAs are key factors for induction of this biogenesis during reproductive-specific stages. © 2014 John Wiley & Sons Ltd.

Sultana Z.,Kyoto University | Sultana Z.,National Institute of Genetics NIG | Asakura A.,Kyoto University
Zootaxa | Year: 2015

The complete larval development of the hermit crab Pagurus maculosus, is described and illustrated based on specimens reared in the laboratory at 15°C and 33-35 PSU. Newly hatched larvae invariably passed through a short prezoeal stage (10 minutes to 2 hours), four zoeal stages (each of 7 days,) and one megalopal stage (14 days). Distinct morphological features of each larval stage of the present study are compared with other closely related species in Japanese waters, and we found many differences in morphology and the duration of zoeal stages between them. We mentioned significant diagnostic characters separating this species from other congeners in Japanese waters that include the presence of red-yellowish chromatophores on the maxillipeds. This is the first report of complete larvae development of Pagurus maculosus. Copyright © 2015 Magnolia Press.

Komiya R.,National Institute of Genetics NIG | Nonomura K.-I.,National Institute of Genetics NIG
Methods in Molecular Biology | Year: 2014

The small noncoding RNAs in plants are categorized into two major classes, 21-nucleotides (nt) micro RNA (miRNA) and 21- or 24-nt small-interfering RNA (siRNA). ARGONAUTE (AGO) proteins associate with small RNAs and play central roles in transcriptional and posttranscriptional gene regulation. In plants, AGO1-miRNA complexes mainly regulate developmental processes, and AGO4-siRNA complexes suppress the activity of transposons and exogenous viral infections via RNA-directed DNA methylation. In many animal species, the PIWI-subfamily AGOs interact with PIWI-interacting RNAs (piRNAs), which are most commonly 24-34 nt, and function to tame transposons and to regulate mRNA translation and stability in the germline. The rice protein MEIOSIS ARRESTED AT LEPTOTENE1 (MEL1) is a plant AGO member that has roles specific to development and maintenance of germ cells before meiosis. MEL1-binding small RNAs are mainly 21 nt, have a 5′-terminal cytosine, and are distinct from animal piRNAs. In this chapter, we describe methods for RNA-immunoprecipitation (RNA-IP) using a specific antibody that recognizes MEL1 and subsequent purification of MEL1-associating small RNAs from the IP fraction. We also introduce the bioinformatic procedures including mapping, annotation, and identifying small RNA clusters on the rice genome. © 2014 Springer Science+Business Media, LLC.

PubMed | National Institute of Genetics NIG and Nagaoka University of Technology
Type: Journal Article | Journal: PloS one | Year: 2016

Caspr3 (Contactin-associated protein-like 3, Cntnap3) is a neural cell adhesion molecule belonging to the Caspr family. We have recently shown that Caspr3 is expressed abundantly between the first and second postnatal weeks in the mouse basal ganglia, including the striatum, external segment of the globus pallidus, subthalamic nucleus, and substantia nigra. However, its physiological role remains largely unknown. In this study, we conducted a series of behavioral analyses on Capsr3-knockout (KO) mice and equivalent wild-type (WT) mice to investigate the role of Caspr3 in brain function. No significant differences were observed in most behavioral traits between Caspr3-KO and WT mice, but we found that Caspr3-KO mice performed poorly during the early phase of the accelerated rotarod task in which latency to falling off a rod rotating with increasing velocity was examined. In the late phase, the performance of the Caspr3-KO mice caught up to the level of WT mice, suggesting that the deletion of Caspr3 caused a delay in motor learning. We then examined changes in neural activity after training on the accelerated rotarod by conducting immunohistochemistry using antibody to c-Fos, an indirect marker for neuronal activity. Experience of the accelerated rotarod task caused increases in the number of c-Fos-positive cells in the dorsal striatum, cerebellum, and motor cortex in both Caspr3-KO and WT mice, but the number of c-Fos-positive cells was significantly lower in the dorsal striatum of Caspr3-KO mice than in that of WT mice. The expression of c-Fos in the ventral striatum of Caspr3-KO and WT mice was not altered by the training. Our findings suggest that reduced activation of neural cells in the dorsal striatum in Caspr3-KO mice leads to a decline in motor learning in the accelerated rotarod task.

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