Hiroyuki Okuno

Hiroyuki Okuno
Kagoshima University | Kadai · Department of Biochemistry II

Ph.D

About

144
Publications
12,030
Reads
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4,749
Citations
Introduction
The focus of my research is to investigate the functions of neuronal immediate early genes (IEGs) on synaptic and cortical plasticity. My ultimate research goal is to elucidate the molecular principles governing memory functions under normal and pathological conditions.
Additional affiliations
April 2018 - present
Kagoshima University Graduate School of Medical and Dental Sciences
Position
  • Professor
July 2013 - March 2018
Kyoto University Graduate School of Medicine
Position
  • Professor (Associate)
June 2003 - June 2013
The University of Tokyo
Position
  • Professor

Publications

Publications (144)
Article
Full-text available
Long-lasting fear-related disorders depend on the excessive retention of traumatic fear memory. We previously showed that the palmitoylation-dependent removal of synaptic α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors prevents hyperexcitation-based epileptic seizures and that AMPA receptor palmitoylation maintains neural network...
Article
Full-text available
Consolidated memory can be preserved or updated depending on the environmental change. Although such conflicting regulation may happen during memory updating, the flexibility of memory updating may have already been determined in the initial memory consolidation process. Here, we explored the gating mechanism for activity-dependent transcription in...
Preprint
Full-text available
The expression of immediate early genes (IEGs) in visual cortex can be triggered by visual input and is associated with certain forms of neuronal plasticity. How IEG expression in cortical neurons relates to neuronal activity or experience-dependent changes of neuronal activity, however, is still unclear. Using three transgenic mouse lines that exp...
Article
Full-text available
Background AMPA receptors predominantly mediate fast excitatory synaptic transmission in the mammalian brain. Post‐translational protein S‐palmitoylation of AMPA receptor GluA subunits at their C‐termini reversibly controls the receptors trafficking to and from excitatory glutamatergic synapses. Excitatory inputs to neurons induce the expression of...
Article
Full-text available
Synaptic AMPAR expression controls the strength of excitatory synaptic transmission and plasticity. An excess of synaptic AMPARs leads to epilepsy in response to seizure-inducible stimulation. The appropriate regulation of AMPARs plays a crucial role in the maintenance of the excitatory/inhibitory synaptic balance; however, the detailed mechanisms...
Article
Full-text available
Neural network remodeling underpins the ability to remember life experiences, but little is known about the long-term plasticity of neural populations. To study how the brain encodes episodic events, we used time-lapse two-photon microscopy and a fluorescent reporter of neural plasticity based on an enhanced form of the synaptic activity-responsive...
Article
Full-text available
The expression of immediate early genes (IEGs) is thought to be an essential molecular basis of neuronal plasticity for higher brain function. Many IEGs contain serum response element (SRE) in their transcriptional regulatory regions and their expression is controlled by serum response factor (SRF). SRF is known to play a role in concert with trans...
Article
Full-text available
In patients born blind with retinal dystrophies, understanding the critical periods of cortical plasticity is important for successful visual restoration. In this study, we sought to model childhood blindness and investigate the plasticity of visual pathways. To this end, we generated double-mutant (Pde6ccpfl1/cpfl1Gnat1IRD2/IRD2) mice with absent...
Article
Plasticity of cortical responses in vivo involves activity-dependent changes at synapses, but the manner in which different forms of synaptic plasticity act together to create functional changes in neurons remains unknown. We found that spike timing–induced receptive field plasticity of visual cortex neurons in mice is anchored by increases in the...
Article
Full-text available
Arc is a unique immediate early gene (IEG) whose expression is induced as synapses are modified during learning. Newly-synthesizedArcmRNA is rapidly transported throughout dendrites and localizes near recently activated synapses.ArcmRNA levels are regulated by rapid degradation, which is accelerated by synaptic activity in a translation-dependent p...
Preprint
Plasticity of cortical responses involves activity-dependent changes at synapses, but the manner in which different forms of synaptic plasticity act together to create functional changes in neuronal responses remains unknown. Here we show that spike-timing induced receptive field plasticity of individual visual cortex neurons in vivo is anchored by...
Article
Long-lasting forms of synaptic plasticity such as long-term potentiation (LTP) and long-term depression (LTD) are fundamental cellular mechanisms underlying learning and memory. The synaptic tagging and capture (STC) hypothesis has provided a theoretical framework on how products of activity-dependent genes may interact with potentiated synapses to...
Article
Full-text available
The molecular basis for the decline in experience-dependent neural plasticity over age remains poorly understood. In visual cortex, the robust plasticity induced in juvenile mice by brief monocular deprivation (MD) during the critical period is abrogated by genetic deletion of Arc, an activity-dependent regulator of excitatory synaptic modification...
Article
Full-text available
The activity-regulated cytoskeleton associated protein Arc is strongly and quickly upregulated by neuronal activity, synaptic potentiation and learning. Arc entry in the synapse is followed by the endocytosis of glutamatergic AMPA receptors (AMPARs), and its nuclear accumulation has been shown in vitro to result in a small decline in the transcript...
Article
Full-text available
Odour information induces various innate responses that are critical to the survival of the individual and for the species. An axon guidance molecule, Neuropilin 2 (Nrp2), is known to mediate targeting of olfactory sensory neurons (primary neurons), to the posteroventral main olfactory bulb (PV MOB) in mice. Here we report that Nrp2-positive (Nrp2+...
Preprint
Full-text available
The molecular basis for the decline in experience-dependent neural plasticity over age remains poorly understood. In visual cortex, the robust plasticity induced in juvenile mice by brief monocular deprivation (MD) during the critical period is abrogated by genetic deletion of Arc, an activity-dependent regulator of excitatory synaptic modification...
Chapter
Long-term synaptic plasticity and memory formation require activity-dependent gene expression. However, it remains unknown how such activity-induced gene products are targeted to proper cellular compartments including synapses. Investigation of the targeting of the memory related-protein Arc from the soma to the synapses have elucidated a novel “in...
Article
Full-text available
Accumulating evidence suggests that transcriptional regulation is required for maintenance of long-term memories (LTMs). Here we characterize global transcriptional and epigenetic changes that occur during LTM storage in the Drosophila mushroom bodies (MBs), structures important for memory. Although LTM formation requires the CREB transcription fac...
Data
FastQC result of the sequencing reads
Data
GO analysis of the CREB/CRTC target genes with decreased H3K9Ac
Data
GO analysis of the CREB/CRTC target genes with increased H4K16Ac
Data
GO analysis of the CREB/CRTC target genes with increased H3K9Ac
Data
GO analysis of the CREB/CRTC target genes with decreased H4K16Ac
Article
Full-text available
In the brain, neuronal gene expression is dynamically changed in response to neuronal activity. In particular, the expression of immediate-early genes (IEGs) such as egr-1, c-fos, and Arc is rapidly and selectively upregulated in subsets of neurons in specific brain regions associated with learning and memory formation. IEG expression has therefore...
Article
Full-text available
In vivo experimental evidence indicates that acute neuronal activation increases Aβ release from presynaptic terminals, whereas long-term effects of chronic synaptic activation on Aβ pathology remain unclear. To address this issue, we adopted optogenetics and transduced stabilized step-function opsin, a channelrhodopsin engineered to elicit a long-...
Article
Full-text available
Although coordinated molecular signaling through excitatory and modulatory neurotransmissions is critical for the induction of immediate early genes (IEGs), which lead to effective changes in synaptic plasticity, the intracellular mechanisms responsible remain obscure. Here we measured the expression of IEGs and used bioluminescence imaging to visu...
Article
Full-text available
We examined the transcriptional regulation of the activity-regulated cytoskeleton-associated protein gene (Arc), focusing on BDNF-induced Arc expression in cultured rat cortical cells. Although the synaptic activity-responsive element (SARE), located -7 kbp upstream of the Arc transcription start site, responded to NMDA, BDNF or FGF2, the proximal...
Article
In an era when every passing week seems to herald the birth of a new area of exploration and a startling new technique to neuroscience, we thought it would be of interest to briefly discuss some promising topics for research on the claustrum. These include immediate-early genes, microRNAs, transcription factors, exosomes, epigenetic mechanisms, mem...
Article
CREB is a pivotal mediator of activity-regulated gene transcription that underlies memory formation and allocation. The contribution of a key CREB cofactor, CREB-regulated transcription coactivator 1 (CRTC1), has, however, remained elusive. Here we show that several constitutive kinase pathways and an activity-regulated phosphatase, calcineurin, co...
Article
The ability to visualize behaviourally evoked neural activity patterns across the rodent brain is essential for understanding the distributed brain networks mediating particular behaviours. However, current imaging methods are limited in their spatial resolution and/or ability to obtain brain-wide coverage of functional activity. Here, we describe...
Article
Full-text available
Genetic labeling of neurons with a specific response feature is an emerging technology for precise dissection of brain circuits that are functionally heterogeneous at the single-cell level. While immediate early gene mapping has been widely used for decades to identify brain regions which are activated by external stimuli, recent characterization o...
Article
During learning and memory, it has been suggested that the coordinated electrical activity of hippocampal neurons translates information about the external environment into internal neuronal representations, which then are stored initially within the hippocampus and subsequently into other areas of the brain. A widely held hypothesis posits that sy...
Article
Abstract Neurons make contact with each other and form neuronal networks. The synapse, the site of contact between 2 neurons, has the ability to dynamically modify functional efficiency and connectivity in response to spatially and temporally specific patterns of neuronal activity. Such plastic ability of the synapse is believed to be indispensable...
Article
Full-text available
Identifying the neuronal ensembles that respond to specific stimuli and mapping their projection patterns in living animals are fundamental challenges in neuroscience. To this end, we engineered a synthetic promoter, the enhanced synaptic activity-responsive element (E-SARE), that drives neuronal activity-dependent gene expression more potently tha...
Article
Neural circuits are shaped by activity-dependent elimination of redundant synapses during postnatal development. In many systems, postsynaptic activity is known to be crucial, but the precise mechanisms remain elusive. Here, we report that the immediate early gene Arc/Arg3.1 mediates elimination of surplus climbing fiber (CF) to Purkinje cell (PC)...
Article
Full-text available
How information encoded in glutamate release rates at individual synapses is converted into biochemical activation patterns of postsynaptic enzymes remains unexplored. To address this, we developed a dual fluorescence resonance energy transfer (FRET) imaging platform and recorded CaMKIIα and calcineurin activities in hippocampal neurons while varyi...
Article
Full-text available
An increasing prevalence of mental health problems has been partly ascribed to abnormal brain development that is induced upon exposure to environmental chemicals. However, it has been extremely difficult to detect and assess such causality particularly at low exposure levels. To address this question, we here investigated higher brain function in...
Data
c-Fos-positive cells in each brain area as estimated by stereological analysis. Bars, open, red, and green, indicate the Control, TC-0.6, and TC-3.0 groups of mice, respectively (mean ± S.E.M, n = 5/group). * indicates a significant difference from other two groups. (P<0.05, two-way ANOVA followed by Tukey's post hoc test). (TIF)
Data
The exploratory and spontaneous activity indices extracted from the acclimation phase 1 of IntelliCage test. Data are shown as average ± S.E.M., n = 8/group. (DOC)
Data
Validation of Arc antibody in Western blotting. Western blotting was performed by the essentially same method as described previously (Kawashima et al., 2009). Mouse brain homogenates (10 µg protein/lane) were separated on standard SDS-polyacrylamide gels and transferred onto nylon membranes. The membranes were allowed to react with the anti-Arc pA...
Data
Photographs of mice in IntelliCage apparatus. (A) Group-housed condition in IntelliCage. (B) Nose poking behavior in a corner chamber. An inset and a large picture each shows a mouse that is before and doing a nose poke. (TIF)
Data
Basal activity in open field test and motor coordination tested by accelerating rota rod test. No significant difference in the average travel distance and time spent in the center area (25 cm×25 cm) among groups was detected (A, B). No significant difference in latency to fall-down among groups was detected in accelerating rota rod test (C). Data...
Data
Correlation coefficient matrix of 16 behavioral parameters described in Table S2 in Control (A), TC-0.6 (B) and TC-3.0 (C) mice. Numbers in the table indicate the correlation coefficient between the corresponding two parameters. Bold face indicates a significant correlation (P<0.05, test of significance for Pearson product-moment correlation coeffi...
Data
Averaged time spent per visit (visit duration) during the first three 5-minute time frames after the task started throughout the behavioral flexibility test. Bars, open, red, and green, indicate the Control, TC-0.6, and TC-3.0 groups of mice, respectively (mean ± S.E.M, n = 8/group). (TIF)
Data
Descriptions of observed behavioral variables extracted from IntelliCage test (prepared for Figure S4). (DOC)
Article
Full-text available
We are interested in identifying and characterizing various projection neurons that constitute the neocortical circuit. For this purpose, we developed a novel lentiviral vector that carries the tetracycline transactivator (tTA) and the transgene under the TET Responsive Element promoter (TRE) on a single backbone. By pseudotyping such a vector with...
Article
Full-text available
Neurons express new gene transcripts and proteins upon receiving synaptic inputs, and these events are essential for achieving proper neuronal wiring, adequate synaptic plasticity, and updatable memory. However, the biological impact of new gene expression on input-specific synaptic potentiation remains largely elusive, in part because the cell bio...
Article
The Arc/Arg3.1 gene product is rapidly upregulated by strong synaptic activity and critically contributes to weakening synapses by promoting AMPA-R endocytosis. However, how activity-induced Arc is redistributed and determines the synapses to be weakened remains unclear. Here, we show targeting of Arc to inactive synapses via a high-affinity intera...