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Susumu Tonegawa

Joshua Kim, Michele Pignatelli, Sangyu Xu, Shigeyoshi Itohara, Susumu Tonegawa
The basolateral amygdala (BLA) is a site of convergence of negative and positive stimuli and is critical for emotional behaviors and associations. However, the neural substrate for negative and positive behaviors and relationship between negative and positive representations in the basolateral amygdala are unknown. Here we identify two genetically distinct, spatially segregated populations of excitatory neurons in the mouse BLA that participate in valence-specific behaviors and are connected through mutual inhibition...
October 17, 2016: Nature Neuroscience
Teruhiro Okuyama, Takashi Kitamura, Dheeraj S Roy, Shigeyoshi Itohara, Susumu Tonegawa
The medial temporal lobe, including the hippocampus, has been implicated in social memory. However, it remains unknown which parts of these brain regions and their circuits hold social memory. Here, we show that ventral hippocampal CA1 (vCA1) neurons of a mouse and their projections to nucleus accumbens (NAc) shell play a necessary and sufficient role in social memory. Both the proportion of activated vCA1 cells and the strength and stability of the responding cells are greater in response to a familiar mouse than to a previously unencountered mouse...
September 30, 2016: Science
Mu-Ming Poo, Michele Pignatelli, Tomás J Ryan, Susumu Tonegawa, Tobias Bonhoeffer, Kelsey C Martin, Andrii Rudenko, Li-Huei Tsai, Richard W Tsien, Gord Fishell, Caitlin Mullins, J Tiago Gonçalves, Matthew Shtrahman, Stephen T Johnston, Fred H Gage, Yang Dan, John Long, György Buzsáki, Charles Stevens
The mechanism of memory remains one of the great unsolved problems of biology. Grappling with the question more than a hundred years ago, the German zoologist Richard Semon formulated the concept of the engram, lasting connections in the brain that result from simultaneous "excitations", whose precise physical nature and consequences were out of reach of the biology of his day. Neuroscientists now have the knowledge and tools to tackle this question, however, and this Forum brings together leading contemporary views on the mechanisms of memory and what the engram means today...
2016: BMC Biology
Fritz Melchers
Fifty years ago, Norbert Hilschmann discovered that antibodies have variable immunoglobulin domains to bind antigens, and constant domains to carry out effector functions in the immune system. Just as this happened, the author of this perspective entered the field of immunology. Ten years later, the genetic basis of antibody variability was discovered by Susumu Tonegawa and his colleagues at the Basel Institute for Immunology, where the author had become a scientific member. At the same time, Georges Köhler, a former graduate student of the author's at the Basel Institute, invented with Cesar Milstein at the Laboratory of Molecular Biology in Cambridge, England, the method to produce monoclonal antibodies...
January 2016: European Journal of Immunology
Dheeraj S Roy, Autumn Arons, Teryn I Mitchell, Michele Pignatelli, Tomás J Ryan, Susumu Tonegawa
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive memory decline and subsequent loss of broader cognitive functions. Memory decline in the early stages of AD is mostly limited to episodic memory, for which the hippocampus has a crucial role. However, it has been uncertain whether the observed amnesia in the early stages of AD is due to disrupted encoding and consolidation of episodic information, or an impairment in the retrieval of stored memory information. Here we show that in transgenic mouse models of early AD, direct optogenetic activation of hippocampal memory engram cells results in memory retrieval despite the fact that these mice are amnesic in long-term memory tests when natural recall cues are used, revealing a retrieval, rather than a storage impairment...
March 24, 2016: Nature
Tomás J Ryan, Susumu Tonegawa
No abstract text is available yet for this article.
April 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Tomás J Ryan, Susumu Tonegawa
No abstract text is available yet for this article.
January 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Susumu Tonegawa, Keikantse Matlhagela
No abstract text is available yet for this article.
October 22, 2015: Nature
Takashi Kitamura, Chen Sun, Jared Martin, Lacey J Kitch, Mark J Schnitzer, Susumu Tonegawa
Forming distinct representations and memories of multiple contexts and episodes is thought to be a crucial function of the hippocampal-entorhinal cortical network. The hippocampal dentate gyrus (DG) and CA3 are known to contribute to these functions, but the role of the entorhinal cortex (EC) is poorly understood. Here, we show that Ocean cells, excitatory stellate neurons in the medial EC layer II projecting into DG and CA3, rapidly form a distinct representation of a novel context and drive context-specific activation of downstream CA3 cells as well as context-specific fear memory...
September 23, 2015: Neuron
Susumu Tonegawa, Xu Liu, Steve Ramirez, Roger Redondo
The idea that memory is stored in the brain as physical alterations goes back at least as far as Plato, but further conceptualization of this idea had to wait until the 20(th) century when two guiding theories were presented: the "engram theory" of Richard Semon and Donald Hebb's "synaptic plasticity theory." While a large number of studies have been conducted since, each supporting some aspect of each of these theories, until recently integrative evidence for the existence of engram cells and circuits as defined by the theories was lacking...
September 2, 2015: Neuron
Takashi Kitamura, Christopher J Macdonald, Susumu Tonegawa
The entorhinal cortex (EC)-hippocampal (HPC) network plays an essential role for episodic memory, which preserves spatial and temporal information about the occurrence of past events. Although there has been significant progress toward understanding the neural circuits underlying the spatial dimension of episodic memory, the relevant circuits subserving the temporal dimension are just beginning to be understood. In this review, we examine the evidence concerning the role of the EC in associating events separated by time--or temporal associative learning--with emphasis on the function of persistent activity in the medial entorhinal cortex layer III (MECIII) and their direct inputs into the CA1 region of HPC...
September 2015: Learning & Memory
Susumu Tonegawa, Michele Pignatelli, Dheeraj S Roy, Tomás J Ryan
A great deal of experimental investment is directed towards questions regarding the mechanisms of memory storage. Such studies have traditionally been restricted to investigation of the anatomical structures, physiological processes, and molecular pathways necessary for the capacity of memory storage, and have avoided the question of how individual memories are stored in the brain. Memory engram technology allows the labeling and subsequent manipulation of components of specific memory engrams in particular brain regions, and it has been established that cell ensembles labeled by this method are both sufficient and necessary for memory recall...
December 2015: Current Opinion in Neurobiology
Joshua Sariñana, Susumu Tonegawa
Activation of prefrontal cortical (PFC), striatal, and hippocampal dopamine 1-class receptors (D1R and D5R) is necessary for normal spatial information processing. Yet the precise role of the D1R versus the D5R in the aforementioned structures, and their specific contribution to the water-maze spatial learning task remains unknown. D1R- and D5R-specific in situ hybridization probes showed that forebrain restricted D1R and D5R KO mice (F-D1R/D5R KO) displayed D1R mRNA deletion in the medial (m)PFC, dorsal and ventral striatum, and the dentate gyrus (DG) of the hippocampus...
January 2016: Hippocampus
Chen Sun, Takashi Kitamura, Jun Yamamoto, Jared Martin, Michele Pignatelli, Lacey J Kitch, Mark J Schnitzer, Susumu Tonegawa
Entorhinal-hippocampal circuits in the mammalian brain are crucial for an animal's spatial and episodic experience, but the neural basis for different spatial computations remain unknown. Medial entorhinal cortex layer II contains pyramidal island and stellate ocean cells. Here, we performed cell type-specific Ca(2+) imaging in freely exploring mice using cellular markers and a miniature head-mounted fluorescence microscope. We found that both oceans and islands contain grid cells in similar proportions, but island cell activity, including activity in a proportion of grid cells, is significantly more speed modulated than ocean cell activity...
July 28, 2015: Proceedings of the National Academy of Sciences of the United States of America
Katie C Bittner, Christine Grienberger, Sachin P Vaidya, Aaron D Milstein, John J Macklin, Junghyup Suh, Susumu Tonegawa, Jeffrey C Magee
Feature-selective firing allows networks to produce representations of the external and internal environments. Despite its importance, the mechanisms generating neuronal feature selectivity are incompletely understood. In many cortical microcircuits the integration of two functionally distinct inputs occurs nonlinearly through generation of active dendritic signals that drive burst firing and robust plasticity. To examine the role of this processing in feature selectivity, we recorded CA1 pyramidal neuron membrane potential and local field potential in mice running on a linear treadmill...
August 2015: Nature Neuroscience
Susumu Tonegawa, Karen Carniol
No abstract text is available yet for this article.
2014: Cold Spring Harbor Symposia on Quantitative Biology
Steve Ramirez, Xu Liu, Christopher J MacDonald, Anthony Moffa, Joanne Zhou, Roger L Redondo, Susumu Tonegawa
Stress is considered a potent environmental risk factor for many behavioural abnormalities, including anxiety and mood disorders. Animal models can exhibit limited but quantifiable behavioural impairments resulting from chronic stress, including deficits in motivation, abnormal responses to behavioural challenges, and anhedonia. The hippocampus is thought to negatively regulate the stress response and to mediate various cognitive and mnemonic aspects of stress-induced impairments, although the neuronal underpinnings sufficient to support behavioural improvements are largely unknown...
June 18, 2015: Nature
Tomás J Ryan, Dheeraj S Roy, Michele Pignatelli, Autumn Arons, Susumu Tonegawa
Memory consolidation is the process by which a newly formed and unstable memory transforms into a stable long-term memory. It is unknown whether the process of memory consolidation occurs exclusively through the stabilization of memory engrams. By using learning-dependent cell labeling, we identified an increase of synaptic strength and dendritic spine density specifically in consolidated memory engram cells. Although these properties are lacking in engram cells under protein synthesis inhibitor-induced amnesia, direct optogenetic activation of these cells results in memory retrieval, and this correlates with retained engram cell-specific connectivity...
May 29, 2015: Science
Xu Liu, Steve Ramirez, Roger L Redondo, Susumu Tonegawa
How memories are formed and stored in the brain remains a fascinating question in neuroscience. Here we discuss the memory engram theory, our recent attempt to identify and manipulate memory engram cells in the brain with optogenetics, and how these methods are used to address questions such as how false memory is formed and how the valence of a memory can be changed in the brain.
2014: Cold Spring Harbor Symposia on Quantitative Biology
Roger L Redondo, Joshua Kim, Autumn L Arons, Steve Ramirez, Xu Liu, Susumu Tonegawa
The valence of memories is malleable because of their intrinsic reconstructive property. This property of memory has been used clinically to treat maladaptive behaviours. However, the neuronal mechanisms and brain circuits that enable the switching of the valence of memories remain largely unknown. Here we investigated these mechanisms by applying the recently developed memory engram cell- manipulation technique. We labelled with channelrhodopsin-2 (ChR2) a population of cells in either the dorsal dentate gyrus (DG) of the hippocampus or the basolateral complex of the amygdala (BLA) that were specifically activated during contextual fear or reward conditioning...
September 18, 2014: Nature
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