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N-methyl-D-aspartate receptors play important roles in acquisition and expression of the eyeblink conditioned response in glutamate receptor subunit delta2 mutant mice.
Classical eyeblink conditioning has been known to depend critically on the cerebellum. Apparently consistent with this, glutamate receptor subunit delta2 null mutant mice, which have serious morphological and functional deficiencies in the cerebellar cortex, are severely impaired in delay paradigm. However, these mutant mice successfully learn in trace paradigm, even in \u270-trace paradigm,\u27 in which the unconditioned stimulus starts just after the conditioned stimulus terminates. Our previous studies revealed that the hippocampus and the muscarinic acetylcholine receptors play crucial roles in 0-trace paradigm in glutamate receptor subunit delta2 null mutant mice unlike in wild-type mice, suggesting a large contribution of the forebrain to 0-trace conditioning in this type of mutant mice. In the present study, we investigated the role of N-methyl-D-aspartate receptors in 0-trace eyeblink conditioning in glutamate receptor subunit delta2 null mutant mice. Mice were injected intraperitoneally with the noncompetitive N-methyl-d-aspartate receptor antagonist (+)MK-801 (0.1mg/kg) or saline, and conditioned with 350-ms tone conditioned stimulus followed by 100-ms periorbital shock unconditioned stimulus. Glutamate receptor subunit delta2 null mutant mice that received (+)MK-801 injection exhibited a severe impairment in acquisition of the conditioned response, compared with the saline-injected glutamate receptor subunit delta2 null mutant mice. In contrast, wild-type mice were not impaired in acquisition of 0-trace conditioned response by (+)MK-801 injection. After the injection solution was changed from (+)MK-801 to saline, glutamate receptor subunit delta2 null mutant mice showed a rapid and partial recovery of performance of the conditioned response. On the other hand, when the injection solution was changed from saline to (+)MK-801, glutamate receptor subunit delta2 null mutant mice showed a marked impairment in expression of the pre-acquired conditioned response, whereas impairment of the expression was small in wild-type mice. Injection of (+)MK-801 had no significant effects on spontaneous eyeblink frequency or startle eyeblink frequency to the tone conditioned stimulus in either glutamate receptor subunit delta2 null mutant mice or wild-type mice. These results suggest that N-methyl-D-aspartate receptors play critical roles both in acquisition and expression of the conditioned response in 0-trace eyeblink conditioning in glutamate receptor subunit delta2 null mutant mice
ã€ããã·ãã ã ãŠãã€ã·ã§ãŠ : ãŠã©ã° ãã«ã³ã ã ãã³ã»ã€
âIwadeshinobuâ ia tale made in the Middle Ages in Japan. There are multiple âsimilarity of peopleâ in âIwadeshinobuâ.But, In the latter half of the story, people who can not resemble will appear. One of them is âUdaisyouâ. At the end of thestory, âUdaisyouâ is leaving for Yoshino. For that reason, This story is said to be a âTragic love and becoming a retiredâ tale.But, âUdaisyouâ goes out to Yoshino with his friend âSaisyo-Chujyoâ. He should be depressed with tragic love. But, He willgo on a journey with a little fun.That is different from other stories. And, the reason seems to be at âsimilarity of peopleâ. Inthis paper I would like to discover the end of âUdaisyouââs story by analyzing âsimilarity of peopleâ
The hippocampus plays an important role in eyeblink conditioning with a short trace interval in glutamate receptor subunit delta 2 mutant mice.
Mutant mice lacking the glutamate receptor subunit delta2 exhibit changes in the structure and function of the cerebellar cortex. The most prominent functional feature is a deficiency in the long-term depression (LTD) at parallel fiber-Purkinje cell synapses. These mutant mice exhibit severe impairment during delay eyeblink conditioning but learn normally during trace eyeblink conditioning without the cerebellar LTD, even with a 0 trace interval. We investigated the hippocampal contribution to this cerebellar LTD-independent "0 trace interval" learning. The mutant mice whose dorsal hippocampi were aspirated exhibited severe impairment in learning, whereas those that received post-training hippocampal lesions retained the memory. The wild-type mice showed no impairment in either case. These results suggest that the hippocampal component of the eyeblink conditioning task becomes dominant when cerebellar LTD is impaired
Impact of general practice / family medicine training on Japanese junior residents:a descriptive study
Background: Despite international recognition of the impact of general practice / family medicine training on postgraduate training outcomes, there have been few reports from Japan. Methods: Junior residents who participated in community medicine training for one month between 2019 and 2022 were enrolled in the study. The settings were five medical institutions (one hospital and four clinics) that had full-time family doctors. The junior residents were assigned to one of these institutions. The training content mainly consisted of general ambulatory care, home medical care, community-based care, and reflection. The junior residents evaluated themselves at the beginning and end of their training, and the family doctors evaluated the junior residents at the end. The evaluation items were 36 items in 10 areas, based on the objectives outlined in the Guidelines for Residency Training - 2020 Edition, and were rated on a 10-point Likert scale. In the statistical analysis, Wilcoxon signed rank test of two related groups was performed to analyze changes between pre and post self-evaluation, and the effect size r was calculated. Results: Ninety-one junior residents completed the study. Their self-evaluations showed statistically significant increases in all 36 items. The effect size was large in 33 items. The family doctors' evaluation was 8-9 points for all 36 items. Conclusion: General practice / family medicine training may greatly contribute to the acquisition of various required clinical abilities in postgraduate training even in Japan
Structure of the dopamine D2 receptor in complex with the antipsychotic drug spiperone
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éãªæ¢çŽ¢ã»èšèšãå¯èœã«--. 京éœå€§åŠãã¬ã¹ãªãªãŒã¹. 2020-12-24.In addition to the serotonin 5-HT2A receptor (5-HT2AR), the dopamine D2 receptor (D2R) is a key therapeutic target of antipsychotics for the treatment of schizophrenia. The inactive state structures of D2R have been described in complex with the inverse agonists risperidone (D2Rris) and haloperidol (D2Rhal). Here we describe the structure of human D2R in complex with spiperone (D2Rspi). In D2Rspi, the conformation of the extracellular loop (ECL) 2, which composes the ligand-binding pocket, was substantially different from those in D2Rris and D2Rhal, demonstrating that ECL2 in D2R is highly dynamic. Moreover, D2Rspi exhibited an extended binding pocket to accommodate spiperoneâs phenyl ring, which probably contributes to the selectivity of spiperone to D2R and 5-HT2AR. Together with D2Rris and D2Rhal, the structural information of D2Rspi should be of value for designing novel antipsychotics with improved safety and efficacy
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