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Kyogo S Kobayashi, Naoki Matsuo, Persistent representation of the environment in the hippocampus., Cell Reports, 10.1016/j.celrep.2022.111989, 42, 1, 111989-111989, 2023.01, In the hippocampus, environmental changes elicit rearrangement of active neuronal ensembles or remapping of place cells. However, it remains elusive how the brain ensures a consistent representation of a certain environment itself despite salient events occurring there. Here, we longitudinally tracked calcium dynamics of dorsal hippocampal CA1 neurons in mice subjected to contextual fear conditioning and extinction training. Overall population activities were significantly changed by fear conditioning and were responsive to footshocks and freezing. However, a small subset of neurons, termed environment cells, were consistently active in a specific environment irrespective of experiences. A decoder modeling study showed that these cells, but not place cells, were able to predict the environment to which the mouse was exposed. Environment cells might underlie the constancy of cognition for distinct environments across time and events. Additionally, our study highlights the functional heterogeneity of cells in the hippocampus.. |
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Kensuke Ikenaka, Kaori Kawai, Masahisa Katsuno, Zhe Huang, Yue-Mei Jiang, Yohei Iguchi, Kyogo Kobayashi, Tsubasa Kimata, Masahiro Waza, Fumiaki Tanaka, Ikue Mori, Gen Sobue, dnc-1/dynactin 1 Knockdown Disrupts Transport of Autophagosomes and Induces Motor Neuron Degeneration, PLOS ONE, 10.1371/journal.pone.0054511, 8, 2, 2013.02, Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons. We previously showed that the expression of dynactin 1, an axon motor protein regulating retrograde transport, is markedly reduced in spinal motor neurons of sporadic ALS patients, although the mechanisms by which decreased dynactin 1 levels cause neurodegeneration have yet to be elucidated. The accumulation of autophagosomes in degenerated motor neurons is another key pathological feature of sporadic ALS. Since autophagosomes are cargo of dynein/dynactin complexes and play a crucial role in the turnover of several organelles and proteins, we hypothesized that the quantitative loss of dynactin 1 disrupts the transport of autophagosomes and induces the degeneration of motor neuron. In the present study, we generated a Caenorhabditis elegans model in which the expression of DNC-1, the homolog of dynactin 1, is specifically knocked down in motor neurons. This model exhibited severe motor defects together with axonal and neuronal degeneration. We also observed impaired movement and increased number of autophagosomes in the degenerated neurons. Furthermore, the combination of rapamycin, an activator of autophagy, and trichostatin which facilitates axonal transport dramatically ameliorated the motor phenotype and axonal degeneration of this model. Thus, our results suggest that decreased expression of dynactin 1 induces motor neuron degeneration and that the transport of autophagosomes is a novel and substantial therapeutic target for motor neuron degeneration..  |
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Kyogo Kobayashi, Shunji Nakano, Mutsuki Amano, Daisuke Tsuboi, Tomoki Nishioka, Shingo Ikeda, Genta Yokoyama, Kozo Kaibuchi, Ikue Mori, Single-Cell Memory Regulates a Neural Circuit for Sensory Behavior, Cell Reports, 10.1016/j.celrep.2015.11.064, 14, 1, 11-21, 2016.01, Unveiling the molecular and cellular mechanisms underlying memory has been a challenge for the past few decades. Although synaptic plasticity is proven to be essential for memory formation, the significance of "single-cell memory'' still remains elusive. Here, we exploited a primary culture system for the analysis of C. elegans neurons and show that a single thermosensory neuron has an ability to form, retain, and reset a temperature memory. Genetic and proteomic analyses found that the expression of the single-cell memory exhibits inter-individual variability, which is controlled by the evolutionarily conserved CaMKI/IV and Raf pathway. The variable responses of a sensory neuron influenced the neural activity of downstream interneurons, suggesting that modulation of the sensory neurons ultimately determines the behavioral output in C. elegans. Our results provide proof of single-cell memory and suggest that the individual differences in neural responses at the single-cell level can confer individuality.. |
