NOBEL LECTURE: The Molecular Biology of Memory Storage: A Dialog Between Genes and Synapses

Kandel, Eric R.

doi:10.1023/a:1014775008533

Cited by 265 publications

(104 citation statements)

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“…Transcriptional regulation of signaling and synaptic components has been found to couple neural activity with longterm changes in synaptic strength (32,46,47). The transcription factor CREB, for example, is modulated by phosphorylation to couple a variety of physiological stimuli to the differential expression of downstream genes that mediate synaptic and behavioral plasticity (48)(49)(50).…”

Section: Activation Of Unc-86 Causes Hypersensitivity To Odor-attractantmentioning

confidence: 99%

“…Drosophila Cfla and islet (26,27) and C. elegans unc-30 (28,29) regulate neurotransmitter production and packaging in particular neurons. There is evidence from many systems that the expression of synaptic components is modulated by neural activity and that changes in synaptic strength underlie neural and behavioral plasticity (30)(31)(32). An outstanding question is whether the activity of transcription factors that trigger cascades of synaptic-component gene expression during initial neurogenesis is also regulated by neural activity in mature neurons to mediate changes in synaptic strength.…”

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confidence: 99%

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Activity of the Caenorhabditis elegans UNC-86 POU transcription factor modulates olfactory sensitivity

Sze

Ruvkun

2003

Proc. Natl. Acad. Sci. U.S.A.

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The activity of transcription factors modulates several neural pathways that mediate complex behaviors. We describe here the role of the POU transcription factor UNC-86 in the olfactory behavior of Caenorhabditis elegans. unc-86-null mutants are defective in response to odor attractants but avoid odor repellents normally. Continuous UNC-86 activity is necessary for maintenance of odortaxis behavior; hyperactivation of UNC-86 by fusion to a VP16 activation domain dramatically enhances sensitivity to odor attractants and promotes odor-attractant adaptation. UNC-86 is not expressed in olfactory sensory neurons but is expressed throughout the life of the animal in the AIZ interneurons of the odorsensory pathway. We suggest that UNC-86 transcriptional activity regulates the expression of genes that mediate synaptic properties of AIZ and that hyperactive UNC-86::VP16 may enhance the expression of synaptic components to affect the capacity to analyze and process sensory information. O dor sensation involves a neural pathway that translates the perception of volatile compounds into motor outputs such as attraction, avoidance, feeding, and mating. To generate such behaviors, an animal recognizes odors, integrates temporal and spatial changes in sensory information, and adjusts its movement. The olfactory system allows animals to sense potential food, danger, and mates. Influenced by previous odorant exposure and other experiences, the sensitivity of an animal to a given odorant may vary over a wide range. Although signal-transduction cascades in olfactory sensory neurons have been explored extensively (1, 2) and molecular mechanisms for plasticity of sensory signaling pathways are beginning to emerge (3-5), neural pathways that integrate and relay odorant stimuli to motor outputs and the mechanisms of behavioral modulation are largely unknown.Odor sensation and the neurons that mediate olfactory behaviors have been analyzed in Caenorhabditis elegans. Odorants stimulate one of two alternative responses: taxis (attraction) or avoidance. Five pairs of olfactory sensory neurons sense volatile chemicals; each pair detects distinct odorants (6). For example, the AWA neurons detect the attractants diacetyl and pyrazine, the AWC neurons detect the attractants benzaldehyde and isoamyl alcohol, and the AWB neurons detect the repellent nonanone (7). The olfactory sensory neurons extend their dendrites to the tip of the nose and project their axons to the nerve ring (the C. elegans CNS equivalent), where they synapse extensively to the interneurons AIY and AIZ, which connect to command interneurons and motor neurons (8). Neural connectivity, genetic analysis (9, 10), and laser-ablation experiments (7) all implicate the AIZ interneurons as a prominent integrating center that couples odorsensory signals to the behavioral response. After continuous exposure to an odorant, C. elegans displays diminished response to the odorant. This olfactory-adaptation behavior is modulated by the availability of food (11,12).The POU transcription fact...

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Section: Activation Of Unc-86 Causes Hypersensitivity To Odor-attractantmentioning

confidence: 99%

mentioning

confidence: 99%

Activity of the Caenorhabditis elegans UNC-86 POU transcription factor modulates olfactory sensitivity

Sze

Ruvkun

2003

Proc. Natl. Acad. Sci. U.S.A.

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“…Besonderes Augenmerk gilt der "Amyloidhypothese" der Alzheimer-Krankheit, da sie das theoretische Fundament für die meisten der in der Entwicklung befindlichen therapeutischen Konzepte bildet. [4,5] Die Entwicklung des episodischen Gedächtnisses beruht insbesondere auf den neuronalen Kopplungen in den kleinen Regionen des entorhinalen Cortex und des Hippocampus im mittleren Schläfenlappen (Hippocampus und Gyrus parahippocampalis). Die gewaltigen Mengen an Information, die durch Sehen, Hören und Fühlen gewonnen werden, werden im Neocortex verarbeitet und durch Projektionen von fast allen Regionen des Neocortex zur entorhinalen Region weitergeleitet (Abbildung 1).…”

Section: Beeinträchtigung Des Episodischen Gedächtnissesunclassified

Die Alzheimer‐Demenz: von der Pathologie zu therapeutischen Ansätzen

Jakob‐Roetne

Jacobsen

2009

Angewandte Chemie

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Die gegenwärtigen Strategien zur Entwicklung von Alzheimer‐Therapien sind breit gefächert. Ein verstärktes Augenmerk gilt der Suche nach Hemmstoffen (siehe Bild für zwei Beispiele) der proteolytischen Enzyme β‐ und γ‐Secretase, die die Spaltung des Amyloid‐Vorläuferproteins in Amyloid‐β‐Peptide inhibieren, aus denen die krankheitstypischen Plaque‐Ablagerungen im Gehirn von Alzheimer‐Patienten entstehen.magnified imageDie Forschungen über Altersdemenz und die Alzheimersche Krankheit umfassen ein sehr breites Feld wissenschaftlicher Aktivitäten. So wurden etwa bei der letztjährigen internationalen Tagung der Alzheimer‐Gesellschaft (ICAD 2008 in Chicago) mehr als 2200 Einzelbeiträge präsentiert. Ziel dieses Aufsatzes ist es, einen zusammenhängenden Überblick über das Gebiet zu präsentieren und die wichtigsten Themen und Forschungstrends aufzuzeigen. Die Ausführungen beginnen mit einer Diskussion von Verhaltensabweichungen und sichtbaren pathologischen Befunden, bevor dann auf die molekularen Details der Pathologie eingegangen wird. Besonderes Augenmerk gilt der “Amyloidhypothese” der Alzheimer‐Krankheit, da sie das theoretische Fundament für die meisten der in der Entwicklung befindlichen therapeutischen Konzepte bildet.

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“…Neuronal AMPA receptors may also associate with other transmembrane proteins, including CNIH (cornichon) proteins and CKAMP44, which can further modulate receptor trafficking and channel function (11)(12)(13)(14). AMPA receptors play fundamental roles in controlling behavior, learning, and memory; dysfunction of these receptors likely underlies a variety of neuropsychiatric disorders (15)(16)(17)(18)(19)(20)(21). Accordingly, numerous pharmacological efforts have sought either to promote AMPA receptor function with potentiators or to block channel function with antagonists.…”

mentioning

confidence: 99%

Transmembrane AMPA Receptor Regulatory Proteins and Cornichon-2 Allosterically Regulate AMPA Receptor Antagonists and Potentiators

Schober

Gill

et al. 2011

Journal of Biological Chemistry

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NOBEL LECTURE: The Molecular Biology of Memory Storage: A Dialog Between Genes and Synapses

Abstract: The biology of learning, and short-term and long-term memory, as revealed by Aplysia and other organisms, is reviewed.

Cited by 265 publications

References 103 publications

Activity of the Caenorhabditis elegans UNC-86 POU transcription factor modulates olfactory sensitivity

Activity of the Caenorhabditis elegans UNC-86 POU transcription factor modulates olfactory sensitivity

Die Alzheimer‐Demenz: von der Pathologie zu therapeutischen Ansätzen

Transmembrane AMPA Receptor Regulatory Proteins and Cornichon-2 Allosterically Regulate AMPA Receptor Antagonists and Potentiators

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