Publications by authors named "Satoshi Kida"

101 Publications

The dopamine D2 agonist quinpirole impairs frontal mismatch responses to sound frequency deviations in freely moving rats.

Neuropsychopharmacol Rep 2021 Jul 23. Epub 2021 Jul 23.

Department of Molecular Neurobiology, Brain Research Institute, Niigata University, Niigata, Japan.

Aim: A reduced mismatch negativity (MMN) response is a promising electrophysiological endophenotype of schizophrenia that reflects neurocognitive impairment. Dopamine dysfunction is associated with symptoms of schizophrenia. However, whether the dopamine system is involved in MMN impairment remains controversial. In this study, we investigated the effects of the dopamine D2-like receptor agonist quinpirole on mismatch responses to sound frequency changes in an animal model.

Methods: Event-related potentials were recorded from electrocorticogram electrodes placed on the auditory and frontal cortices of freely moving rats using a frequency oddball paradigm consisting of ascending and equiprobable (ie, many standards) control sequences before and after the subcutaneous administration of quinpirole. To detect mismatch responses, difference waveforms were obtained by subtracting nondeviant control waveforms from deviant waveforms.

Results: Here, we show the significant effects of quinpirole on frontal mismatch responses to sound frequency deviations in rats. Quinpirole delayed the frontal N18 and P30 mismatch responses and reduced the frontal N55 MMN-like response, which resulted from the reduction in the N55 amplitude to deviant stimuli. Importantly, the magnitude of the N55 amplitude was negatively correlated with the time of the P30 latency in the difference waveforms. In contrast, quinpirole administration did not clearly affect the temporal mismatch responses recorded from the auditory cortex.

Conclusion: These results suggest that the disruption of dopamine D2-like receptor signaling by quinpirole reduces frontal MMN to sound frequency deviations and that delays in early mismatch responses are involved in this MMN impairment.
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http://dx.doi.org/10.1002/npr2.12199DOI Listing
July 2021

The efficacy of memantine in the treatment of civilian posttraumatic stress disorder: an open-label trial.

Eur J Psychotraumatol 2021 Jan 15;12(1):1859821. Epub 2021 Jan 15.

Department of Behavioral Medicine, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan.

: Currently, there is a paucity of pharmacological treatment options for posttraumatic stress disorder (PTSD), and the development of a novel pharmacotherapeutic approach has become a matter of great interest. : We conducted a 12-week open-label clinical trial to examine the efficacy and safety of memantine, an -methyl-D-aspartate receptor antagonist, in the treatment of civilian PTSD. : Thirteen adult patients with DSM-IV PTSD, all civilian women, were enrolled. They were monitored at an ambulatory care facility every week until 4 weeks and then every 4 weeks until 12 weeks. Memantine was added to each patient's current medication, with the initial dosage of 5 mg/day and then titrated. Concomitant medications were essentially kept unchanged during the trial. The primary outcome was PTSD diagnosis and severity assessed with the Posttraumatic Diagnostic Scale (PDS). : Of the 13 cases, one dropped out and two were discarded due to the protocol deviation, and the analysis was done for the remaining 10. Mean PDS total scores decreased from 32.3 ± 9.7 at baseline to 12.2 ± 7.9 at endpoint, which was statistically significant with a large effect (paired -test: = .002, = 1.35); intrusion, avoidance, hyperarousal symptoms were all significantly improved from baseline to endpoint. Six patients no longer fulfilled the diagnostic criteria of PTSD at endpoint. Some adverse, but not serious, effects possibly related to memantine were observed, including sleep problems, sleepiness, sedation, weight change and hypotension. : Memantine significantly reduced PTSD symptoms in civilian female PTSD patients and the drug was well tolerated. Future randomized controlled trials are necessary to verify the efficacy and safety of memantine in the treatment of PTSD.
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http://dx.doi.org/10.1080/20008198.2020.1859821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874937PMC
January 2021

Tumor necrosis factor α negatively regulates the retrieval and reconsolidation of hippocampus-dependent memory.

Brain Behav Immun 2021 05 5;94:79-88. Epub 2021 Mar 5.

Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan; Department of Bioscience, Faculty of Life Sciences, Tokyo University of Agriculture, Tokyo 156-8502, Japan. Electronic address:

Neural inflammation is associated with cognitive decline, especially learning and memory. Tumor necrosis factor α (TNFα) is a major cytokine generated during neuroinflammation. Previous studies indicated that TNFα impairs hippocampus-dependent memory including contextual fear and spatial memories. However, it is unknown which memory processes are impaired by TNFα. Here, we show that TNFα blocked the retrieval and reconsolidation of contextual fear and spatial memories. Micro-infusion of TNFα into the dorsal hippocampus at 6-18 h before retrieval impaired the retrieval of contextual fear memory, although micro-infusion before contextual fear conditioning had no effect on memory formation. Interestingly, hippocampal TNFα micro-infusion before memory retrieval decreased freezing responses, even at 24 h after retrieval, suggesting that TNFα impairs the reconsolidation of contextual fear memory. Similarly, hippocampal TNFα micro-infusion impaired the retrieval and reconsolidation of spatial memory in the Morris water maze. Consistent with these observations, hippocampal TNFα micro-infusion before retrieval blocked the induction of c-fos expression in the hippocampus, which is a marker of neural activation, in response to the retrieval of contextual fear memory. Collectively, our findings indicate that TNFα negatively regulates the retrieval and reconsolidation of hippocampus-dependent memory.
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http://dx.doi.org/10.1016/j.bbi.2021.02.033DOI Listing
May 2021

Dietary magnesium deficiency induces the expression of neuroinflammation-related genes in mouse brain.

Neuropsychopharmacol Rep 2021 Jun 6;41(2):230-236. Epub 2021 Mar 6.

Department of Applied Biological Chemistry, Graduate school of Agriculture and Life Sciences, The University of Tokyo, Tokyo, Japan.

Aims: Dietary Mg deficiency (MgD) impairs hippocampus-dependent memory in mice; however, the molecular mechanisms underlying MgD-induced memory impairments are unclear. Here, we investigated the molecular signatures in the hippocampus of MgD mice by analyzing the hippocampal transcriptome.

Methods: We performed RNA-sequencing of the hippocampal transcriptome of MgD mice. We used gene ontology analyses and quantitative real-time PCR to validate the RNA-sequencing results.

Results: mRNAs for neuroinflammation-related genes were upregulated in the hippocampus and cortex of MgD mice.

Conclusion: MgD induces neuroinflammation in the mouse brain, including the hippocampus and cortex. Our findings suggest that MgD-induced neuroinflammation triggers the impairments of hippocampus-dependent memory.
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http://dx.doi.org/10.1002/npr2.12167DOI Listing
June 2021

LOTUS, an endogenous Nogo receptor antagonist, is involved in synapse and memory formation.

Sci Rep 2021 Mar 3;11(1):5085. Epub 2021 Mar 3.

Molecular Medical Bioscience Laboratory, Yokohama City University Graduate School of Medical Life Science, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan.

The Nogo signal is involved in impairment of memory formation. We previously reported the lateral olfactory tract usher substance (LOTUS) as an endogenous antagonist of the Nogo receptor 1 that mediates the inhibition of axon growth and synapse formation. Moreover, we found that LOTUS plays an essential role in neural circuit formation and nerve regeneration. However, the effects of LOTUS on synapse formation and memory function have not been elucidated. Here, we clearly showed the involvement of LOTUS in synapse formation and memory function. The cultured hippocampal neurons derived from lotus gene knockout (LOTUS-KO) mice exhibited a decrease in synaptic density compared with those from wild-type mice. We also found decrease of dendritic spine formation in the adult hippocampus of LOTUS-KO mice. Finally, we demonstrated that LOTUS deficiency impairs memory formation in the social recognition test and the Morris water maze test, indicating that LOTUS is involved in functions of social and spatial learning and memory. These findings suggest that LOTUS affects synapse formation and memory function.
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http://dx.doi.org/10.1038/s41598-021-84106-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930056PMC
March 2021

Interactions between the amygdala and medial prefrontal cortex as upstream regulators of the hippocampus to reconsolidate and enhance retrieved inhibitory avoidance memory.

Mol Brain 2021 03 2;14(1):44. Epub 2021 Mar 2.

Department of Bioscience, Faculty of Life Sciences, Tokyo University of Agriculture, 1-1-1, Sakuragaoka, Setagaya-ku, Tokyo, 156-8502, Japan.

Memory reconsolidation is thought to maintain or enhance an original memory or add new information to the memory. Retrieved inhibitory avoidance (IA) memory is enhanced through memory reconsolidation by activating gene expression in the amygdala, medial prefrontal cortex (mPFC), and hippocampus. However, it remains unclear how these regions interact to reconsolidate/enhance IA memory. Here, we found the interactions between the amygdala and mPFC as upstream regulators of the hippocampus for IA memory reconsolidation. Pharmacological inactivation of the amygdala, mPFC, or hippocampus immediately after IA memory retrieval blocked IA memory enhancement. More importantly, inactivation of the amygdala or mPFC blocked the induction of c-Fos in the amygdala, mPFC, and hippocampus, whereas hippocampal blockade inhibited it only in the hippocampus. These observations suggest interactions between the amygdala and mPFC and they both function as upstream regulators of the hippocampus to reconsolidate IA memory. Our findings suggest circuitry mechanisms underlying IA memory enhancement through reconsolidation between the amygdala, mPFC, and hippocampus.
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http://dx.doi.org/10.1186/s13041-021-00753-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923328PMC
March 2021

Active Transition of Fear Memory Phase from Reconsolidation to Extinction through ERK-Mediated Prevention of Reconsolidation.

J Neurosci 2021 02 8;41(6):1288-1300. Epub 2020 Dec 8.

Department of Bioscience, Faculty of Life Sciences, Tokyo University of Agriculture, Tokyo 156-8502, Japan

The retrieval of fear memory induces two opposite memory process, i.e., reconsolidation and extinction. Brief retrieval induces reconsolidation to maintain or enhance fear memory, while prolonged retrieval extinguishes this memory. Although the mechanisms of reconsolidation and extinction have been investigated, it remains unknown how fear memory phases are switched from reconsolidation to extinction during memory retrieval. Here, we show that an extracellular signal-regulated kinase (ERK)-dependent memory transition process after retrieval regulates the switch of memory phases from reconsolidation to extinction by preventing induction of reconsolidation in an inhibitory avoidance (IA) task in male mice. First, the transition memory phase, which cancels the induction of reconsolidation, but is insufficient for the acquisition of extinction, was identified after reconsolidation, but before extinction phases. Second, the reconsolidation, transition, and extinction phases after memory retrieval showed distinct molecular and cellular signatures through cAMP responsive element binding protein (CREB) and ERK phosphorylation in the amygdala, hippocampus, and medial prefrontal cortex (mPFC). The reconsolidation phase showed increased CREB phosphorylation, while the extinction phase displayed several neural populations with various combinations of CREB and/or ERK phosphorylation, in these brain regions. Interestingly, the three memory phases, including the transition phase, showed transient ERK activation immediately after retrieval. Most importantly, the blockade of ERK in the amygdala, hippocampus, or mPFC at the transition memory phase disinhibited reconsolidation-induced enhancement of IA memory. These observations suggest that the ERK-signaling pathway actively regulates the transition of memory phase from reconsolidation to extinction and this process functions as a switch that cancels reconsolidation of fear memory. Retrieval of fear memory induces two opposite memory process; reconsolidation and extinction. Reconsolidation maintains/enhances fear memory, while extinction weakens fear memory. It remains unknown how memory phases are switched from reconsolidation to extinction during retrieval. Here, we identified an active memory transition process functioning as a switch that inhibits reconsolidation. This memory transition phase showed a transient increase of extracellular signal-regulated kinase (ERK) phosphorylation in the amygdala, hippocampus and medial prefrontal cortex (mPFC). Interestingly, inhibition of ERK in these regions at the transition phase disinhibited the reconsolidation-mediated enhancement of inhibitory avoidance (IA) memory. These findings suggest that the transition memory process actively regulates the switch of fear memory phases of fear memory by preventing induction of reconsolidation through the activation of the ERK-signaling pathway.
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http://dx.doi.org/10.1523/JNEUROSCI.1854-20.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888227PMC
February 2021

[Recent Review Articles in Radiological Physics and Technology].

Nihon Hoshasen Gijutsu Gakkai Zasshi 2020 ;76(11):1207-1210

Faculty of Engineering, Gifu University.

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http://dx.doi.org/10.6009/jjrt.2020_JSRT_76.11.1207DOI Listing
December 2020

[Improvement in Image Quality of CBCT during Treatment by Cycle Generative Adversarial Network].

Nihon Hoshasen Gijutsu Gakkai Zasshi 2020 ;76(11):1173-1184

Department of Radiology, University of Tokyo Hospital.

Purpose: Volumetric modulated arc therapy (VMAT) can acquire projection images during rotational irradiation, and cone-beam computed tomography (CBCT) images during VMAT delivery can be reconstructed. The poor quality of CBCT images prevents accurate recognition of organ position during the treatment. The purpose of this study was to improve the image quality of CBCT during the treatment by cycle generative adversarial network (CycleGAN).

Method: Twenty patients with clinically localized prostate cancer were treated with VMAT, and projection images for intra-treatment CBCT (iCBCT) were acquired. Synthesis of PCT (SynPCT) with improved image quality by CycleGAN requires only unpaired and unaligned iCBCT and planning CT (PCT) images for training. We performed visual and quantitative evaluation to compare iCBCT, SynPCT and PCT deformable image registration (DIR) to confirm the clinical usefulness.

Result: We demonstrated suitable CycleGAN networks and hyperparameters for SynPCT. The image quality of SynPCT improved visually and quantitatively while preserving anatomical structures of the original iCBCT. The undesirable deformation of PCT was reduced when SynPCT was used as its reference instead of iCBCT.

Conclusion: We have performed image synthesis with preservation of organ position by CycleGAN for iCBCT and confirmed the clinical usefulness.
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http://dx.doi.org/10.6009/jjrt.2020_JSRT_76.11.1173DOI Listing
November 2020

Assessment of dysplasia in bone marrow smear with convolutional neural network.

Sci Rep 2020 09 7;10(1):14734. Epub 2020 Sep 7.

Department of Hemato-Oncology, International Medical Center, Saitama Medical University, Saitama, Japan.

In this study, we developed the world's first artificial intelligence (AI) system that assesses the dysplasia of blood cells on bone marrow smears and presents the result of AI prediction for one of the most representative dysplasia-decreased granules (DG). We photographed field images from the bone marrow smears from patients with myelodysplastic syndrome (MDS) or non-MDS diseases and cropped each cell using an originally developed cell detector. Two morphologists labelled each cell. The degree of dysplasia was evaluated on a four-point scale: 0-3 (e.g., neutrophil with severely decreased granules were labelled DG3). We then constructed the classifier from the dataset of labelled images. The detector and classifier were based on a deep neural network pre-trained with natural images. We obtained 1797 labelled images, and the morphologists determined 134 DGs (DG1: 46, DG2: 77, DG3: 11). Subsequently, we performed a five-fold cross-validation to evaluate the performance of the classifier. For DG1-3 labelled by morphologists, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 91.0%, 97.7%, 76.3%, 99.3%, and 97.2%, respectively. When DG1 was excluded in the process, the sensitivity, specificity, PPV, NPV, and accuracy were 85.2%, 98.9%, 80.6%, and 99.2% and 98.2%, respectively.
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http://dx.doi.org/10.1038/s41598-020-71752-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477564PMC
September 2020

Function and mechanisms of memory destabilization and reconsolidation after retrieval.

Authors:
Satoshi Kida

Proc Jpn Acad Ser B Phys Biol Sci 2020 ;96(3):95-106

Graduate School of Agriculture and Life Sciences, The University of Tokyo.

Memory retrieval is not a passive process. When a memory is retrieved, the retrieved memory is destabilized, similar to short-term memory just after learning, and requires memory reconsolidation to re-stabilize the memory. Recent studies characterizing destabilization and reconsolidation showed that a retrieved memory is not always destabilized and that there are boundary conditions that determine the induction of destabilization and reconsolidation according to certain parameters, such as the duration of retrieval and the memory strength and age. Moreover, the reconsolidation of contextual fear memory is not independent of memory extinction; rather, these memory processes interact with each other. There is an increasing number of findings suggesting that destabilization following retrieval facilitates the modification, weakening, or strengthening of the original memory, and the resultant updated memory is stabilized through reconsolidation. Reconsolidation could be targeted therapeutically to improve emotional disorders such as post-traumatic stress disorder and phobia. Thus, this review summarizes recent findings to understand the mechanisms and function of reconsolidation.
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http://dx.doi.org/10.2183/pjab.96.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167366PMC
April 2020

Hippocampal clock regulates memory retrieval via Dopamine and PKA-induced GluA1 phosphorylation.

Nat Commun 2019 12 18;10(1):5766. Epub 2019 Dec 18.

Department of Bioscience, Faculty of Applied Bioscience, Tokyo University of Agriculture, Tokyo, 156-8502, Japan.

Cognitive performance in people varies according to time-of-day, with memory retrieval declining in the late afternoon-early evening. However, functional roles of local brain circadian clocks in memory performance remains unclear. Here, we show that hippocampal clock controlled by the circadian-dependent transcription factor BMAL1 regulates time-of-day retrieval profile. Inducible transgenic dominant negative BMAL1 (dnBMAL1) expression in mouse forebrain or hippocampus disrupted retrieval of hippocampal memories at Zeitgeber Time 8-12, independently of retention delay, encoding time and Zeitgeber entrainment cue. This altered retrieval profile was associated with downregulation of hippocampal Dopamine-cAMP signaling in dnBMAL1 mice. These changes included decreases in Dopamine Receptors (D1-R and D5-R) and GluA1-S845 phosphorylation by PKA. Consistently, pharmacological activation of cAMP-signals or D1/5Rs rescued impaired retrieval in dnBMAL1 mice. Importantly, GluA1 S845A knock-in mice showed similar retrieval deficits with dnBMAL1 mice. Our findings suggest mechanisms underlying regulation of retrieval by hippocampal clock through D1/5R-cAMP-PKA-mediated GluA1 phosphorylation.
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http://dx.doi.org/10.1038/s41467-019-13554-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920429PMC
December 2019

Visual enhancement of Cone-beam CT by use of CycleGAN.

Med Phys 2020 Mar 3;47(3):998-1010. Epub 2020 Jan 3.

Department of Radiology, University of Tokyo Hospital, Tokyo, 113-8655, Japan.

Purpose: Cone-beam computed tomography (CBCT) offers advantages over conventional fan-beam CT in that it requires a shorter time and less exposure to obtain images. However, CBCT images suffer from low soft-tissue contrast, noise, and artifacts compared to conventional fan-beam CT images. Therefore, it is essential to improve the image quality of CBCT.

Methods: In this paper, we propose a synthetic approach to translate CBCT images with deep neural networks. Our method requires only unpaired and unaligned CBCT images and planning fan-beam CT (PlanCT) images for training. The CBCT images and PlanCT images may be obtained from other patients as long as they are acquired with the same scanner settings. Once trained, three-dimensionally reconstructed CBCT images can be directly translated into high-quality PlanCT-like images.

Results: We demonstrate the effectiveness of our method with images obtained from 20 prostate patients, and provide a statistical and visual comparison. The image quality of the translated images shows substantial improvement in voxel values, spatial uniformity, and artifact suppression compared to those of the original CBCT. The anatomical structures of the original CBCT images were also well preserved in the translated images.

Conclusions: Our method produces visually PlanCT-like images from CBCT images while preserving anatomical structures.
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http://dx.doi.org/10.1002/mp.13963DOI Listing
March 2020

Improvement of PTSD-like behavior by the forgetting effect of hippocampal neurogenesis enhancer memantine in a social defeat stress paradigm.

Mol Brain 2019 08 2;12(1):68. Epub 2019 Aug 2.

Department of Bioscience, Faculty of Applied Bioscience, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo, 156-8502, Japan.

Post-traumatic stress disorder (PTSD) is a psychiatric disorder associated with memories of traumatic experiences. Recent studies have shown that the forgetting of contextual fear memory is promoted via increased adult hippocampal neurogenesis induced by neurogenesis enhancers, such as memantine (MEM) and exercise, raising the possibility that neurogenesis enhancers improve PTSD by facilitating the forgetting of traumatic memory. On the other hand, repeated exposure to social defeat (SD) stress by aggressor mice induces social avoidance behavior to the aggressor and chronic anxiety-like behavior. In this study, we assumed this SD stress paradigm as a PTSD-like model and examined the effects of treatment with neurogenesis enhancer MEM on SD stress-induced PTSD-like behavior. Male C57BL/6 mice received SD stress for 10 consecutive days and were assessed for social avoidance memory to the aggressor (memory of aggressor mice) and anxiety-like behavior using social interaction and elevated zero maze tasks. Consistent with previous studies, SD mice formed social avoidance memory and exhibited increased anxiety-like behavior. Importantly, subsequent MEM treatment (once a week for 4 weeks) significantly reduced social avoidance behavior, suggesting that MEM-treated SD mice showed forgetting of social avoidance memory. Interestingly, MEM-treated SD mice showed comparable anxiety-like behavior with control mice that were not exposed to SD stress. Moreover, MEM-treated SD mice showed no reinstatement of social avoidance memory following single re-exposure to the aggressor. Our findings suggest that neurogenesis enhancer not only enhanced the forgetting of traumatic memory but also improved PTSD (anxiety)-like behavior.
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http://dx.doi.org/10.1186/s13041-019-0488-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6676601PMC
August 2019

Overview of image-to-image translation by use of deep neural networks: denoising, super-resolution, modality conversion, and reconstruction in medical imaging.

Radiol Phys Technol 2019 Sep 20;12(3):235-248. Epub 2019 Jun 20.

LPixel Inc., Tokyo, Japan.

Since the advent of deep convolutional neural networks (DNNs), computer vision has seen an extremely rapid progress that has led to huge advances in medical imaging. Every year, many new methods are reported at conferences such as the International Conference on Medical Image Computing and Computer-Assisted Intervention and Machine Learning for Medical Image Reconstruction, or published online at the preprint server arXiv. There is a plethora of surveys on applications of neural networks in medical imaging (see [1] for a relatively recent comprehensive survey). This article does not aim to cover all aspects of the field, but focuses on a particular topic, image-to-image translation. Although the topic may not sound familiar, it turns out that many seemingly irrelevant applications can be understood as instances of image-to-image translation. Such applications include (1) noise reduction, (2) super-resolution, (3) image synthesis, and (4) reconstruction. The same underlying principles and algorithms work for various tasks. Our aim is to introduce some of the key ideas on this topic from a uniform viewpoint. We introduce core ideas and jargon that are specific to image processing by use of DNNs. Having an intuitive grasp of the core ideas of applications of neural networks in medical imaging and a knowledge of technical terms would be of great help to the reader for understanding the existing and future applications. Most of the recent applications which build on image-to-image translation are based on one of two fundamental architectures, called pix2pix and CycleGAN, depending on whether the available training data are paired or unpaired (see Sect. 1.3). We provide codes ([2, 3]) which implement these two architectures with various enhancements. Our codes are available online with use of the very permissive MIT license. We provide a hands-on tutorial for training a model for denoising based on our codes (see Sect. 6). We hope that this article, together with the codes, will provide both an overview and the details of the key algorithms and that it will serve as a basis for the development of new applications.
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http://dx.doi.org/10.1007/s12194-019-00520-yDOI Listing
September 2019

Dietary heat-killed Lactobacillus brevis SBC8803 (SBL88™) improves hippocampus-dependent memory performance and adult hippocampal neurogenesis.

Neuropsychopharmacol Rep 2019 06 11;39(2):140-145. Epub 2019 Apr 11.

Department of Bioscience, Faculty of Applied Bioscience, Tokyo University of Agriculture, Setagaya-ku, Tokyo, Japan.

Aims: Lactobacillus species are used widely as various food and supplements to improve health. Previous studies have shown that heat-killed Lactobacillus brevis SBC8803 induces serotonin release from intestinal cells and affects sleep rhythm and the autonomic nervous system. However, the effect of SBC8803 on cognitive function remains unknown. Here, we examined the effects of dietary heat-killed SBC8803 on hippocampus-dependent memory and adult hippocampal neurogenesis.

Methods: Hippocampus-dependent memory performance was assessed in mice fed heat-killed SBC8803 using social recognition and contextual fear conditioning tasks. Adult hippocampal neurogenesis was evaluated before, during, and after feeding heat-killed SBC8803 by measuring the number of 5-bromo-2-deoxyuridine (BrdU)-positive cells following systemic injections of BrdU using immunohistochemistry.

Results: Mice fed a heat-killed SBC8803 diet showed an improvement of hippocampus-dependent social recognition and contextual fear memories and enhanced adult hippocampal neurogenesis by increasing the survival, but not proliferation, of newborn neurons.

Conclusion: Dietary heat-killed SBC8803 functions as memory and neurogenesis enhancers.
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http://dx.doi.org/10.1002/npr2.12054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7292330PMC
June 2019

Motor skills mediated through cerebellothalamic tracts projecting to the central lateral nucleus.

Mol Brain 2019 02 8;12(1):13. Epub 2019 Feb 8.

Department of Molecular Genetics, Institute of Biomedical Sciences, Fukushima Medical University, Fukushima, 960-1295, Japan.

The cerebellum regulates complex animal behaviors, such as motor control and spatial recognition, through communication with many other brain regions. The major targets of the cerebellar projections are the thalamic regions including the ventroanterior nucleus (VA) and ventrolateral nucleus (VL). Another thalamic target is the central lateral nucleus (CL), which receives the innervations mainly from the dentate nucleus (DN) in the cerebellum. Although previous electrophysiological studies suggest the role of the CL as the relay of cerebellar functions, the kinds of behavioral functions mediated by cerebellothalamic tracts projecting to the CL remain unknown. Here, we used immunotoxin (IT) targeting technology combined with a neuron-specific retrograde labeling technique, and selectively eliminated the cerebellothalamic tracts of mice. We confirmed that the number of neurons in the DN was selectively decreased by the IT treatment. These IT-treated mice showed normal overground locomotion with no ataxic behavior. However, elimination of these neurons impaired motor coordination in the rotarod test and forelimb movement in the reaching test. These mice showed intact acquisition and flexible change of spatial information processing in the place discrimination, Morris water maze, and T-maze tests. Although the tract labeling indicated the existence of axonal collaterals of the DN-CL pathway to the rostral part of the VA/VL complex, excitatory lesion of the rostral VA/VL did not show any significant alterations in motor coordination or forelimb reaching, suggesting no requirement of axonal branches connecting to the VL/VA complex for motor skill function. Taken together, our data highlight that the cerebellothalamic tracts projecting to the CL play a key role in the control of motor skills, including motor coordination and forelimb reaching, but not spatial recognition and its flexibility.
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http://dx.doi.org/10.1186/s13041-019-0431-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6368787PMC
February 2019

NSP-C contributes to the upregulation of CLOCK/BMAL1-mediated transcription.

Cytotechnology 2019 Feb 1;71(1):453-460. Epub 2019 Jan 1.

Department of Bioscience, Faculty of Life Science, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo, 156-8502, Japan.

The bHLH-PAS transcription factors clock circadian regulator (CLOCK) and brain and muscle ARNT-like protein 1 (BMAL1) play essential roles in the generation of circadian gene expression rhythms through the activation of E-box-mediated transcription. Importantly, circadian transcriptional rhythms mediated by CLOCK/BMAL1 are observed in peripheral tissues as well as in the suprachiasmatic nucleus and contribute to tissue-specific functions. These findings suggest that CLOCK/BMAL1 have roles in many biological phenomena by interacting with various cellular regulators. In the present study, to understand the mechanisms underlying the multiple functional roles of CLOCK, we tried to identify new proteins that interact with CLOCK using a yeast two-hybrid system. We identified neuroendocrine-specific protein (NSP)-C, which is highly expressed in the brain, as a positive regulator of CLOCK/BMAL1-mediated transcription. We found that NSP-C interacted with CLOCK in mammalian cells. Co-expression of NSP-C with CLOCK/BMAL1 enhanced the transcriptional activation by CLOCK/BMAL1. Furthermore, knockdown of endogenous NSP-C by small interfering RNA (siRNA) suppressed E-box-mediated transcription, while this reduction of transcription was rescued by the expression of NSP-C protected from the action of siRNA. These observations suggest that NSP-C contributes to the upregulation of CLOCK/BMAL1-mediated transcription.
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http://dx.doi.org/10.1007/s10616-018-0266-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6368517PMC
February 2019

Dietary magnesium deficiency impairs hippocampus-dependent memories without changes in the spine density and morphology of hippocampal neurons in mice.

Brain Res Bull 2019 01 27;144:149-157. Epub 2018 Nov 27.

Department of Bioscience, Faculty of Life Science, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502, Japan. Electronic address:

Magnesium (Mg) is an essential mineral for maintaining biological functions. One major action of Mg in the brain is modulating the voltage-dependent blockade of N-methyl-d-aspartate type glutamate receptors, thereby controlling their opening, which is crucial for synaptic plasticity. Therefore, Mg has been shown to play critical roles in learning and memory, and synaptic plasticity. However, the effects of dietary Mg deficiency (MgD) on learning and memory and the morphology of neurons contributing to memory performance have not been examined in depth. Here, we show that MgD impairs hippocampus-dependent memories in mice. Mice fed an MgD diet showed deficits in hippocampus-dependent contextual fear, spatial and social recognition memories, although they showed normal amygdala- and insular cortex-dependent conditioned taste aversion memory, locomotor activity, and emotional behaviors such as anxiety-related and social behaviors. However, MgD mice showed normal spine density and morphology of hippocampal neurons. These findings suggest that MgD impairs hippocampus-dependent memory without affecting the morphology of hippocampal neurons.
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http://dx.doi.org/10.1016/j.brainresbull.2018.11.019DOI Listing
January 2019

Reconsolidation/destabilization, extinction and forgetting of fear memory as therapeutic targets for PTSD.

Authors:
Satoshi Kida

Psychopharmacology (Berl) 2019 Jan 29;236(1):49-57. Epub 2018 Oct 29.

Department of Bioscience, Faculty of Life Science, Tokyo University of Agriculture, Tokyo, Japan.

Post-traumatic stress disorder (PTSD) is a psychiatric disorder associated with memories of traumatic experiences. Conditioned fear memory, a representative model of traumatic memories, is observed across species from lower to higher animals, including humans. Numerous studies have investigated the mechanisms of conditioned fear memory and have led to the identification of the underlying processes involved in fear memory regulation, including cellular and systems consolidation of fear conditioning, destabilization/reconsolidation and extinction after fear memory retrieval, and forgetting of fear memory. These studies suggested that mechanisms for fear memory regulation are shared by humans and other higher animals. Additionally, rodent studies have identified the mechanisms of fear memory at the molecular, cellular, and circuit levels. Findings from these studies in rodents have been applied to facilitate the development and improvement of PTSD intervention. For instance, reconsolidation and extinction of fear memories have been applied for PTSD treatment to improve prolonged exposure (PE) therapy, an effective psychotherapy for PTSD. Combination of medications weakening retrieved traumatic memory (e.g., by facilitating both destabilization and extinction) with PE therapy may contribute to improvement of PTSD. Interestingly, a recent study in mice identified forgetting of fear memory as another potential therapeutic target for PTSD. A better understanding of the mechanisms involved in fear memory processes is likely to facilitate the development of better treatments for PTSD. This review describes fear memory processes and their mechanisms and discusses the pros and cons of applying how this knowledge can be applied in the development of interventions for PTSD.
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http://dx.doi.org/10.1007/s00213-018-5086-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6373183PMC
January 2019

Cone Beam Computed Tomography Image Quality Improvement Using a Deep Convolutional Neural Network.

Cureus 2018 Apr 29;10(4):e2548. Epub 2018 Apr 29.

Radiology, The University of Tokyo Hospital.

Introduction Cone beam computed tomography (CBCT) plays an important role in image-guided radiation therapy (IGRT), while having disadvantages of severe shading artifact caused by the reconstruction using scatter contaminated and truncated projections. The purpose of this study is to develop a deep convolutional neural network (DCNN) method for improving CBCT image quality. Methods CBCT and planning computed tomography (pCT) image pairs from 20 prostate cancer patients were selected. Subsequently, each pCT volume was pre-aligned to the corresponding CBCT volume by image registration, thereby leading to registered pCT data (pCT). Next, a 39-layer DCNN model was trained to learn a direct mapping from the CBCT to the corresponding pCTimages. The trained model was applied to a new CBCT data set to obtain improved CBCT (i-CBCT) images. The resulting i-CBCT images were compared to pCT using the spatial non-uniformity (SNU), the peak-signal-to-noise ratio (PSNR) and the structural similarity index measure (SSIM). Results The image quality of the i-CBCT has shown a substantial improvement on spatial uniformity compared to that of the original CBCT, and a significant improvement on the PSNR and the SSIM compared to that of the original CBCT and the enhanced CBCT by the existing pCT-based correction method. Conclusion We have developed a DCNN method for improving CBCT image quality. The proposed method may be directly applicable to CBCT images acquired by any commercial CBCT scanner.
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http://dx.doi.org/10.7759/cureus.2548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6021187PMC
April 2018

Dietary glucoraphanin prevents the onset of psychosis in the adult offspring after maternal immune activation.

Sci Rep 2018 02 1;8(1):2158. Epub 2018 Feb 1.

Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, 260-8670, Japan.

Maternal immune activation (MIA) contributes to behavioral abnormalities relevant to schizophrenia in adult offspring, although the molecular mechanisms underlying MIA-induced behavioral changes remain unclear. Here we demonstrated that dietary intake of glucoraphanin (GF), the precursor of a natural antioxidant sulforaphane, during juvenile and adolescent stages prevented cognitive deficits and loss of parvalbumin (PV) immunoreactivity in the medial prefrontal cortex (mPFC) of adult offspring after MIA. Gene set enrichment analysis by RNA sequencing showed that MIA caused abnormal expression of centrosome-related genes in the PFC and hippocampus of adult offspring, and that dietary intake of GF improved these abnormal gene expressions. Particularly, MIA increased the expression of suppressor of fermentation-induced loss of stress resistance protein 1 (Sfi1) mRNA in the PFC and hippocampus of adult offspring, and dietary intake of GF prevented the expression of Sfi1 mRNA in these regions. Interestingly, we found altered expression of SFI1 in the postmortem brains and SFI1 mRNA in hair follicle cells from patients with schizophrenia compared with controls. Overall, these data suggest that centrosome-related genes may play a role in the onset of psychosis in offspring after MIA. Therefore, dietary intake of GF-rich vegetables in high-risk psychosis subjects may prevent the transition to psychosis in young adulthood.
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http://dx.doi.org/10.1038/s41598-018-20538-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5794794PMC
February 2018

Hippocampal calpain is required for the consolidation and reconsolidation but not extinction of contextual fear memory.

Mol Brain 2017 Dec 19;10(1):61. Epub 2017 Dec 19.

Department of Bioscience, Faculty of Applied Bioscience, Tokyo University of Agriculture, Tokyo, Japan.

Memory consolidation, reconsolidation, and extinction have been shown to share similar molecular signatures, including new gene expression. Calpain is a Ca-dependent protease that exerts its effects through the proteolytic cleavage of target proteins. Neuron-specific conditional deletions of calpain 1 and 2 impair long-term potentiation in the hippocampus and spatial learning. Moreover, recent studies have suggested distinct roles of calpain 1 and 2 in synaptic plasticity. However, the role of hippocampal calpain in memory processes, especially memory consolidation, reconsolidation, and extinction, is still unclear. In the current study, we demonstrated the critical roles of hippocampal calpain in the consolidation, reconsolidation, and extinction of contextual fear memory in mice. We examined the effects of pharmacological inhibition of calpain in the hippocampus on these memory processes, using the N-Acetyl-Leu-Leu-norleucinal (ALLN; calpain 1 and 2 inhibitor). Microinfusion of ALLN into the dorsal hippocampus impaired long-term memory (24 h memory) without affecting short-term memory (2 h memory). Similarly, this pharmacological blockade of calpain in the dorsal hippocampus also disrupted reactivated memory but did not affect memory extinction. Importantly, the systemic administration of ALLN inhibited the induction of c-fos in the hippocampus, which is observed when memory is consolidated. Our observations showed that hippocampal calpain is required for the consolidation and reconsolidation of contextual fear memory. Further, the results suggested that calpain contributes to the regulation of new gene expression that is necessary for these memory processes as a regulator of Ca-signal transduction pathway.
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http://dx.doi.org/10.1186/s13041-017-0341-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5735908PMC
December 2017

Cone-beam CT reconstruction for non-periodic organ motion using time-ordered chain graph model.

Radiat Oncol 2017 Sep 4;12(1):145. Epub 2017 Sep 4.

Department of Radiology, The University of Tokyo Hospital, Bunkyo-ku, Tokyo, 113-8655, Japan.

Purpose: The purpose of this study is to introduce the new concept of a four-dimensional (4D) cone-beam computed tomography (CBCT) reconstruction approach for non-periodic organ motion in cooperation with the time-ordered chain graph model (TCGM) and to compare it with previously developed methods such as total variation-based compressed sensing (TVCS) and prior-image constrained compressed sensing (PICCS).

Materials And Methods: Our proposed reconstruction is based on a model including the constraint originating from the images of neighboring time phases. Namely, the reconstructed time-series images depend on each other in this TCGM scheme, and the time-ordered images are concurrently reconstructed in the iterative reconstruction approach. In this study, iterative reconstruction with the TCGM was carried out with 90° projection ranges. The images reconstructed by the TCGM were compared with the images reconstructed by TVCS (200° projection ranges) and PICCS (90° projection ranges). Two kinds of projection data sets-an elliptic-cylindrical digital phantom and two clinical patients' data-were used. For the digital phantom, an air sphere was contained and virtually moved along the longitudinal axis by 3 cm/30 s and 3 cm/60 s; the temporal resolution was evaluated by measuring the penumbral width of the air sphere. The clinical feasibility of the non-periodic time-ordered 4D CBCT image reconstruction was examined with the patient data in the pelvic region.

Results: In the evaluation of the digital-phantom reconstruction, the penumbral widths of the TCGM yielded the narrowest result; the results obtained by PICCS and TCGM using 90° projection ranges were 2.8% and 18.2% for 3 cm/30 s, and 5.0% and 23.1% for 3 cm/60 s narrower than that of TVCS using 200° projection ranges. This suggests that the TCGM has a better temporal resolution, whereas PICCS seems similar to TVCS. These reconstruction methods were also compared using patients' projection data sets. Although all three reconstruction results showed motion related to rectal gas or stool, the result obtained by the TCGM was visibly clearer with less blurring.

Conclusion: The TCGM is a feasible approach to visualize non-periodic organ motion. The digital-phantom results demonstrated that the proposed method provides 4D image series with a better temporal resolution compared to TVCS and PICCS. The clinical patients' results also showed that the present method enables us to visualize motion related to rectal gas and flatus in the rectum.
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http://dx.doi.org/10.1186/s13014-017-0879-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5584034PMC
September 2017

Effective atomic number estimation using kV-MV dual-energy source in LINAC.

Phys Med 2017 Jul 20;39:9-15. Epub 2017 Jun 20.

Department of Radiology, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo, Tokyo 113-8655, Japan.

Dual-energy computed tomography (DECT) imaging can measure the effective atomic number (EAN) as well as the electron density, and thus its adoption may improve dose calculations in brachytherapy and external photon/particle therapy. An expanded energy gap in dual-energy sources is expected to yield more accurate EAN estimations than conventional DECT systems, which typically span less than 100kV. The aim of this paper is to assess a larger energy gap DECT by using a linear accelerator (LINAC) radiotherapy system with a kV X-ray imaging device, which are combined to provide X-rays in both the kV- and MV-energy ranges. Traditionally, the EAN is determined by parameterising the Hounsfield Unit; however, this is difficult in a kV-MV DECT due to different uncertainties in the reconstructed attenuation coefficient at each end of the energy spectrum. To overcome this problem, we included a new calibration step to produce the most likely linear attenuation coefficients, based upon the X-ray spectrum. To determine the X-ray spectrum, Monte Carlo calculations using GEANT4 were performed. Then the images were calibrated using information from eight inserts of known materials in a CIRS phantom (CIRS Inc., Norfolk, VA). Agreement between the estimated and empirical EANs in these inserts was within 11%. Validation was subsequently performed with the CatPhan500 phantom (The Phantom Laboratory, Salem). The estimated EAN for seven inserts agreed with the empirical values to within 3%. Accordingly, it can be concluded that, given properly reconstructed images based upon a well-determined X-ray spectrum, kV-MV DECT provides an excellent prediction for the EAN.
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http://dx.doi.org/10.1016/j.ejmp.2017.06.010DOI Listing
July 2017

Brain networks activated to form object recognition memory.

Brain Res Bull 2018 07 3;141:27-34. Epub 2017 Jun 3.

Department of Biosciences, Faculty of Applied Bioscience, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Saitama 332-0012, Japan. Electronic address:

Object recognition memory allows discrimination of familiar and novel objects. Previous studies have shown the importance of several brain regions for object recognition memories; however, the mechanisms underlying the consolidation of object recognition (OR) memory at the anatomic level remain unknown. Here, we analyzed the brain network for the generation of OR memory in mice by measuring the expression of the immediate-early gene c-fos. We found that c-fos expression was induced in the hippocampus (CA1 and CA3 regions), insular cortex (IC), perirhinal cortex (PRh), and medial prefrontal cortex (mPFC) when OR memory was generated, suggesting that gene expression in these brain regions contributes to the formation of OR memory. Consistently, inhibition of protein synthesis in the mPFC blocked the formation of long-term OR memory. Importantly, network analyses suggested that the hippocampus, IC, PRh and mPFC show increased connectivity with other brain regions when OR memory is formed. Thus, we suggest that a brain network composed of the hippocampus, IC, PRh, and mPFC is required for the generation of OR memory by connecting with other brain regions.
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http://dx.doi.org/10.1016/j.brainresbull.2017.05.017DOI Listing
July 2018

Functional Connectivity of Multiple Brain Regions Required for the Consolidation of Social Recognition Memory.

J Neurosci 2017 04 14;37(15):4103-4116. Epub 2017 Mar 14.

Department of Biosciences, Faculty of Applied Bioscience, Tokyo University of Agriculture, Tokyo 156-8502, Japan,

Social recognition memory is an essential and basic component of social behavior that is used to discriminate familiar and novel animals/humans. Previous studies have shown the importance of several brain regions for social recognition memories; however, the mechanisms underlying the consolidation of social recognition memory at the molecular and anatomic levels remain unknown. Here, we show a brain network necessary for the generation of social recognition memory in mice. A mouse genetic study showed that cAMP-responsive element-binding protein (CREB)-mediated transcription is required for the formation of social recognition memory. Importantly, significant inductions of the CREB target immediate-early genes c-fos and Arc were observed in the hippocampus (CA1 and CA3 regions), medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), and amygdala (basolateral region) when social recognition memory was generated. Pharmacological experiments using a microinfusion of the protein synthesis inhibitor anisomycin showed that protein synthesis in these brain regions is required for the consolidation of social recognition memory. These findings suggested that social recognition memory is consolidated through the activation of CREB-mediated gene expression in the hippocampus/mPFC/ACC/amygdala. Network analyses suggested that these four brain regions show functional connectivity with other brain regions and, more importantly, that the hippocampus functions as a hub to integrate brain networks and generate social recognition memory, whereas the ACC and amygdala are important for coordinating brain activity when social interaction is initiated by connecting with other brain regions. We have found that a brain network composed of the hippocampus/mPFC/ACC/amygdala is required for the consolidation of social recognition memory. Here, we identify brain networks composed of multiple brain regions for the consolidation of social recognition memory. We found that social recognition memory is consolidated through CREB-meditated gene expression in the hippocampus, medial prefrontal cortex, anterior cingulate cortex (ACC), and amygdala. Importantly, network analyses based on c-fos expression suggest that functional connectivity of these four brain regions with other brain regions is increased with time spent in social investigation toward the generation of brain networks to consolidate social recognition memory. Furthermore, our findings suggest that hippocampus functions as a hub to integrate brain networks and generate social recognition memory, whereas ACC and amygdala are important for coordinating brain activity when social interaction is initiated by connecting with other brain regions.
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http://dx.doi.org/10.1523/JNEUROSCI.3451-16.2017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6596582PMC
April 2017

Constitutive activation of CREB in mice enhances temporal association learning and increases hippocampal CA1 neuronal spine density and complexity.

Sci Rep 2017 02 14;7:42528. Epub 2017 Feb 14.

Department of Bioscience, Faculty of Applied Bioscience, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502, Japan.

Transcription factor CREB is believed to play essential roles in the formation of long-term memory (LTM), but not in learning and short-term memory (STM). Surprisingly, we previously showed that transgenic mice expressing a dominant active mutant of CREB (DIEDML) in the forebrain (DIEDML mice) demonstrated enhanced STM and LTM in hippocampal-dependent, rapid, one-trial learning tasks. Here we show that constitutive activation of CREB enhances hippocampal-dependent learning of temporal association in trace fear conditioning and delayed matching-to-place tasks. We then show that in DIEDML mice the apical tuft dendrites of hippocampal CA1 pyramidal neurons, required for temporal association learning, display increased spine density, especially of thin spines and of Homer1-negative spines. In contrast, the basal and apical oblique dendrites of CA1 neurons, required for rapid one-trial learning, show increased density of thin, stubby, and mushroom spines and of Homer1-positive spines. Furthermore, DIEDML mice showed increased dendritic complexity in the proximal portion of apical CA1 dendrites to the soma. In contrast, forebrain overexpression of CaMKIV, leading to enhanced LTM but not STM, show normal learning and CA1 neuron morphology. These findings suggest that dendritic region-specific morphological changes in CA1 neurons by constitutive activation of CREB may contribute to improved learning and STM.
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http://dx.doi.org/10.1038/srep42528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5307365PMC
February 2017

Hippocampal neurogenesis enhancers promote forgetting of remote fear memory after hippocampal reactivation by retrieval.

Elife 2016 Sep 26;5. Epub 2016 Sep 26.

Department of Biosciences, Faculty of Applied Bioscience, Tokyo University of Agriculture, Setagaya-ku, Japan.

Forgetting of recent fear memory is promoted by treatment with memantine (MEM), which increases hippocampal neurogenesis. The approaches for treatment of post-traumatic stress disorder (PTSD) using rodent models have focused on the extinction and reconsolidation of recent, but not remote, memories. Here we show that, following prolonged re-exposure to the conditioning context, enhancers of hippocampal neurogenesis, including MEM, promote forgetting of remote contextual fear memory. However, these interventions are ineffective following shorter re-exposures. Importantly, we find that long, but not short re-exposures activate gene expression in the hippocampus and induce hippocampus-dependent reconsolidation of remote contextual fear memory. Furthermore, remote memory retrieval becomes hippocampus-dependent after the long-time recall, suggesting that remote fear memory returns to a hippocampus dependent state after the long-time recall, thereby allowing enhanced forgetting by increased hippocampal neurogenesis. Forgetting of traumatic memory may contribute to the development of PTSD treatment.
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http://dx.doi.org/10.7554/eLife.17464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5036964PMC
September 2016
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