Review
Neurosciences
Konstanze Simbriger, Ines S. Amorim, Gilliard Lach, Kleanthi Chalkiadaki, Stella Kouloulia, Seyed Mehdi Jafarnejad, Arkady Khoutorsky, Christos G. Gkogkas
Summary: Contextual fear conditioning is a common behavioral paradigm used in neuroscience research to study the mechanisms of learning and memory. Using ribosome profiling, a study demonstrated that an immediate shock in male mice leads to translational and transcriptional changes in Immediate Early Genes in the dorsal hippocampus, an effect often overlooked in research.
PROGRESS IN NEUROBIOLOGY
(2021)
Review
Neurosciences
Christine Stubbendorff, Carl W. Stevenson
Summary: Research has shown that dopamine plays a crucial role in regulating various contextual fear processes, although the related neurochemical mechanisms are still not fully understood. Understanding how dopamine regulates contextual fear can provide novel insights into the neurochemical modulation of neural circuit function underlying memory processing.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Jiahui Yu, Toshie Naoi, Masanori Sakaguchi
Summary: Fear generalization is a symptom of anxiety-related disorders, as demonstrated in mice exposed to similar neutral contexts after fear conditioning. This study provides insight into factors influencing fear generalization and may aid future research into the pathophysiological mechanisms of anxiety-related disorders.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Neurosciences
Zhiqian Yu, Mai Sakai, Hotaka Fukushima, Chiaki Ono, Yoshie Kikuchi, Ryuta Koyama, Ko Matsui, Tomoyuki Furuyashiki, Satoshi Kida, Hiroaki Tomita
Summary: This study characterized the transcription profile of microglia in a fear memory conditional mouse model, and found that synapse-related genes were induced while immune-related genes were reduced after fear memory consolidation. The expression of synapse-related genes reversed after fear memory extinction, but immune-related genes remained unchanged. The expression of neurotransmitter release regulators in hippocampal microglia was also found to be correlated with fear memory formation and extinction.
BRAIN RESEARCH BULLETIN
(2022)
Article
Neurosciences
Ana Oliveira, Marcia Azevedo, Rafaela Seixas, Raquel Martinho, Paula Serrao, Monica Moreira-Rodrigues
Summary: Adrenaline and glucose released during stress may strengthen contextual fear memory. Glucose can enhance contextual fear memory independently of adrenaline in Ad-deficient mice, possibly through increased gene expression in the hippocampus. Additionally, adrenaline and glucose may act synergistically to strengthen contextual fear memory.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Neurosciences
Zu-Cheng Shen, Zhi-Xuan Xia, Jian-Min Liu, Jie-Yan Zheng, Yu-Fei Luo, Han Yang, Meng-Die Li, Ting Cao, Hai-Ping Liu, Gui-Lin Jin, Hui-Hui Huang, Chang-Xi Yu, Jun Zhou
Summary: Palmitoylation has been found to be relevant to learning, memory, and disorders such as post-traumatic stress disorder and aging-related cognitive decline. However, the mechanisms underlying palmitoylation in these processes are not well understood. This study investigated the role of palmitoylation in hippocampal synaptic transmission and fear memory formation and identified the involvement of APT1-mediated depalmitoylation in the regulation of glutamatergic synaptic plasticity.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Behavioral Sciences
Carmela Conte, Elisabetta Baldi, Corrado Bucherelli, Raffaella di Vito, Davide Petri, Giovanna Traina
Summary: The contextual fear conditioning (CFC) paradigm is an effective approach for understanding the neurobiology of learning and memory. This study aimed to determine if the response to conditioning and stressful challenge is associated with alterations in synapse-related genes mRNA levels in specific brain regions. The results showed changes in gene expression after exposure to stress and new environment.
NEUROBIOLOGY OF LEARNING AND MEMORY
(2023)
Article
Psychology, Biological
Marcia C. Chavez, Maria Ragusa, Kayla Brooks, Chakeer Drake-Frazier, Isabella Ramos, Megan Zajkowski, Kalynn M. Schulz
Summary: The study found that prenatal and adolescent stress have different effects on fear memory, with no cumulative effects observed in males and females.
PHYSIOLOGY & BEHAVIOR
(2021)
Article
Neurosciences
Megha Sehgal, Vanessa E. Ehlers, James R. Moyer Jr
Summary: New learning results in modulation of intrinsic plasticity in the underlying brain regions. Such changes in intrinsic plasticity can influence allocation and encoding of future memories. In this study, the authors investigated the time course of changes in intrinsic excitability within lateral amygdala neurons using auditory fear conditioning as a behavioral paradigm. They found transient changes in the intrinsic excitability of amygdala neurons, which lasted for up to 4 days post-learning. Additionally, the study showed that the enhanced neuronal intrinsic excitability was evident in many of the same neurons that had undergone synaptic plasticity immediately following fear conditioning.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Neurosciences
Stuart A. Williams, Miriam Gwilt, Rebecca Hock, Charlotte Taylor, Joanna Loayza, Carl W. Stevenson, Helen J. Cassaday, Tobias Bast
Summary: The neural disinhibition in the hippocampus disrupts fear conditioning and salience modulation, which are impaired in schizophrenia. This may be attributed to the disruption in neural processing within the hippocampus and its projection sites.
Article
Neurosciences
Khadijah Shanazz, Rachael Dixon-Melvin, Rebecca Nalloor, Riya Thumar, Almira I. Vazdarjanova
Summary: According to animal experiments, there are differences in the expression of fear memories between female and male rats. Female rats tend to express fear memories through active motor responses, which is referred to as "Anxioescapic" behavior strategy. There is no significant difference in fear learning between female and male rats.
Article
Clinical Neurology
Yi-ting Wu, Chun-hui Chang
Summary: The functional reuniens and rhomboid nuclei are important for the acquisition and expression of fear to context and tones under trace procedure.
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
(2022)
Article
Neurosciences
Lucas A. Marcondes, Jociane De C. Myskiw, Eduarda G. Nachtigall, Rodrigo F. Narvaes, Ivan Izquierdo, Cristiane R. G. Furini
Summary: The prelimbic cortex (PrL) is crucial for encoding and expressing contextual fear memory. Protein kinase M zeta (PKM zeta) has been shown to maintain memories by inhibiting the endocytosis of GluA2-containing AMPA receptors. This study found that acute inhibition of GluA2-dependent AMPAR endocytosis in the PrL does not affect recent or remote contextual fear memory maintenance. However, inhibition of PKM zeta in the PrL at a remote time point disrupts contextual fear memory maintenance, which can be prevented by blocking GluA2-dependent removal of AMPARs.
Article
Neurosciences
Min Soo Kang, Jin-Hee Han
Summary: The study suggests that the hippocampus receiving input from MEC plays a crucial role in the formation of contextual fear memory after learning. Optogenetic inhibition of MEC inputs within 5 minutes after learning reduces freezing behavior during retrieval test, while the same manipulation performed 30 minutes before retrieval test has no effect on fear memory.
Article
Neurosciences
Ana Karla Oliveira Leite, Clarissa Penha Farias, Bianca Estefani Schmidt, Lucas Teixeira, Alessandra Schmitt Rieder, Cristiane R. G. Furini, Angela T. S. Wyse
Summary: This study investigated the effects of acute strength exercise on memory consolidation and found that exercise can promote the consolidation of weak memory. This effect is dependent on the activation of NMDA-receptors, and exercise also modulates the overexpression of BDNF and synapsin I through the activation of NMDA-receptors.
Article
Psychiatry
Hiroko Kotajima-Murakami, Hideo Hagihara, Atsushi Sato, Yoko Hagino, Miho Tanaka, Yoshihisa Katoh, Yasumasa Nishito, Yukio Takamatsu, Shigeo Uchino, Tsuyoshi Miyakawa, Kazutaka Ikeda
Summary: This study found that exposure to the GABA(A) receptor antagonist picrotoxin during the embryonic period induced ASD-like behavior in mice. The offspring exhibited a reduction in active interaction time in social interaction tests, and gene expression analysis showed an increase in odorant receptor gene expression. The findings suggest that impaired odorant function may contribute to social deficits in individuals with ASD.
FRONTIERS IN PSYCHIATRY
(2022)
Article
Biochemistry & Molecular Biology
Takafumi Kawai, Hirotaka Narita, Kohtarou Konno, Sharmin Akter, Rizki Tsari Andriani, Hirohide Iwasaki, Shoji Nishikawa, Norihiko Yokoi, Yuko Fukata, Masaki Fukata, Pattama Wiriyasermkul, Pornparn Kongpracha, Shushi Nagamori, Keizo Takao, Tsuyoshi Miyakawa, Manabu Abe, Kenji Sakimura, Masahiko Watanabe, Atsushi Nakagawa, Yasushi Okamura
Summary: Voltage-sensing protein TMEM266 has a unique voltage-sensing mechanism and interacts with specific splice variants. The coiled-coil region plays a significant role in forming homodimers, and the cytosolic region at the C-terminal of TMEM266 may bind to various targets. TMEM266 deficiency is associated with behavioral abnormalities.
BIOCHEMICAL JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Katsuya Miyajima, Yusuke Sudo, Sho Sanechika, Yoshitaka Hara, Mieko Horiguchi, Feng Xu, Minori Suzuki, Satoshi Hara, Koichi Tanda, Ken-ichi Inoue, Masahiko Takada, Nozomu Yoshioka, Hirohide Takebayashi, Masayo Mori-Kojima, Masahiro Sugimoto, Chiho Sumi-Ichinose, Kazunao Kondo, Keizo Takao, Tsuyoshi Miyakawa, Hiroshi Ichinose
Summary: Increasing evidence suggests that peripheral amino acid metabolism is involved in the pathophysiology of neuropsychiatric disorders, but the molecular mechanisms are largely unknown. This study found that disturbances in tetrahydrobiopterin (BH4) metabolism can lead to hyperphenylalaninemia and monoamine deficiency in the brain, potentially contributing to the development of anxiety-related psychiatric disorders.
JOURNAL OF NEUROCHEMISTRY
(2022)
Article
Neurosciences
Akiko Oota-Ishigaki, Keizo Takao, Daisuke Yamada, Masayuki Sekiguchi, Masayuki Itoh, Yumie Koshidata, Manabu Abe, Rie Natsume, Masaki Kaneko, Toma Adachi, Toshie Kaizuka, Nami Suzuki, Kenji Sakimura, Hiroyuki Okuno, Keiji Wada, Masayoshi Mishina, Tsuyoshi Miyakawa, Takashi Hayashi
Summary: This study suggests that impairment of AMPA receptor palmitoylation specifically causes symptoms resembling posttraumatic stress disorder (PTSD), including prolonged contextual fear memory formation and increased fear generalization. However, this mutation has no effect on anxiety levels, locomotion, sociability, depression-related behaviors, and spatial learning and memory.
NEUROPSYCHOPHARMACOLOGY
(2022)
Article
Developmental Biology
Takayuki Mitsuhashi, Satoko Hattori, Kimino Fujimura, Shinsuke Shibata, Tsuyoshi Miyakawa, Takao Takahashi
Summary: Valproic acid (VPA) is an antiepileptic drug that inhibits epileptic activity of neurons mainly through sodium channel inhibition and GABA transaminase inhibition. It also inhibits histone deacetylases, leading to epigenetic modifications of stem/progenitor cell characteristics and affecting fetal development. Clinical studies have shown that VPA exposure in utero increases the risk of autistic features and intellectual disabilities in children. A study on mice revealed that in utero VPA exposure led to abnormal social interaction, cognitive changes, hypersensitivity to pain/heat, and impaired locomotor activity, resembling symptoms of autism spectrum disorder in humans.
DEVELOPMENTAL NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Shohei Iida, Hirotaka Shoji, Fumihiro Kawakita, Takehisa Nakanishi, Yoshiaki Matsushima, Makoto Kondo, Koji Habe, Hidenori Suzuki, Tsuyoshi Miyakawa, Keiichi Yamanaka
Summary: Intense itching reduces the quality of life and is associated with psychiatric conditions. This study used a dermatitis mouse model to evaluate psychiatric symptoms and found that Lcn2 is closely associated with anxiety symptoms, but anxiety and depression caused by chronic skin inflammation may be irreversible. Active control of skin inflammation is essential for preventing anxiety.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Hirotaka Shoji, Kazutaka Ikeda, Tsuyoshi Miyakawa
Summary: This study investigated the effects of 5-HTT deficiency on behavior, gut microbiota, and brain c-Fos expression. The findings revealed abnormal behaviors including decreased locomotor activity, reduced pain sensitivity, increased anxiety and depression-related behavior, and altered gut microbiota composition in 5-HTT-/- mice. The expression of c-Fos in certain brain regions was also different from normal. These results indicate that 5-HTT-/- mice serve as a valid animal model to study anxiety and depression.
Article
Neurosciences
Mohamed Darwish, Satoko Hattori, Hirofumi Nishizono, Tsuyoshi Miyakawa, Nozomu Yachie, Keizo Takao
Summary: GlyR alpha 4 subunit is mainly expressed in the hindbrain and midbrain of mice, and has lower expression in other regions of the brain. The expression of GlyR alpha 4 increases during brain development. Mutant mice with Glra4 deficiency show changes in startle response, social behavior, and anxiety-like behavior.
Article
Psychiatry
Hideo Hagihara, Tomoyuki Murano, Tsuyoshi Miyakawa
Summary: The study suggests that changes in brain pH, expressed as pH, are associated with various neuropsychiatric disorders. The expression patterns of pH-associated genes in these disorders were analyzed in human patients and mouse models, showing abnormal expression levels. Furthermore, astrocytes were identified as the cell type with the highest acidity-related gene expression. These findings indicate that the expression pattern of pH-associated genes may serve as a surrogate for pH changes in brain cells and provide insights into the pathophysiology of neuropsychiatric disorders.
FRONTIERS IN PSYCHIATRY
(2023)
Article
Biochemistry & Molecular Biology
Yashuang Ping, Kenji Ohata, Kenji Kikushima, Takumi Sakamoto, Ariful Islam, Lili Xu, Hengsen Zhang, Bin Chen, Jing Yan, Fumihiro Eto, Chiho Nakane, Keizo Takao, Tsuyoshi Miyakawa, Katsuya Kabashima, Miho Watanabe, Tomoaki Kahyo, Ikuko Yao, Atsuo Fukuda, Koji Ikegami, Yoshiyuki Konishi, Mitsutoshi Setou
Summary: As an important neurotransmitter, glutamate functions in the majority of excitatory synapses in the human brain. The metabolic pathway of glutamate is complex, and the exact role of glutamate pool in neurons remains unclear. This study utilized Ttll1 and Ttll7 knockout mice to investigate the impact of tubulin polyglutamylation on neuronal behavior. Matrix-assisted laser desorption/ionization (MALDI) Imaging mass spectrometry (IMS) analysis revealed increased levels of glutamate in the brains of knockout mice, suggesting that tubulin polyglutamylation by TTLLs acts as a reservoir of glutamate in neurons and modulates other glutamate-related amino acids.
Article
Neurosciences
Hirotaka Shoji, Hiroshi Kunugi, Tsuyoshi Miyakawa
Summary: This study investigated the acute and chronic effects of oral administration of capric acid (C10) on behavior in mice. The results showed that high doses of C10 decreased body weight, distance traveled, and increased anxiety-like behavior, while low doses of C10 increased distance traveled. Repeated administration of C10 at a high dose for more than 21 days led to lower body weight and decreased depression-related behavior.
NEUROPSYCHOPHARMACOLOGY REPORTS
(2022)
Meeting Abstract
Ophthalmology
Chieko Koike, Tesshu Hori, Keishun Iwao, Shohei Ikuta, Satoko Hattori, Keizo Takao, Tsuyoshi Miyakawa
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
Article
Clinical Neurology
Masayoshi Nagai, Kenji Iemura, Takako Kikkawa, Sharmin Naher, Satoko Hattori, Hideo Hagihara, Koh-ichi Nagata, Hayato Anzawa, Risa Kugisaki, Hideki Wanibuchi, Takaya Abe, Kenichi Inoue, Kengo Kinoshita, Tsuyoshi Miyakawa, Noriko Osumi, Kozo Tanaka
Summary: The deficiency of CHAMP1 gene causes intellectual disability and is associated with delayed neuronal development and behavioral defects observed in mice models.
BRAIN COMMUNICATIONS
(2022)