Impaired learning in mice with abnormal short-lived plasticity

Silva, Alcino J.; Rosahl, Thomas W.; Chapman, Paul F.; Marowitz, Zachary; Friedman, Eugenia; Frankland, Paul W.; Cestari, Vincenzo; Cioffi, Dianna; Südhof, Thomas C.; Bourtchuladze, Roussoudan

doi:10.1016/s0960-9822(96)00756-7

Cited by 163 publications

(126 citation statements)

References 41 publications

(82 reference statements)

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“…tent with previous studies demonstrating that synapsin I knockout mice have seemingly normal LTP and learning (Rosahl et al, 1993;Silva et al, 1996), reflecting a functional redundancy between synapsin I and II (Rosahl et al, 1995;Silva et al, 1996). Accordingly, synapsin I/II double mutants show synaptic and learning deficits absent in either single gene mutant (Rosahl et al, 1995;Silva et al, 1996).…”

Section: Figure 8 Ltp Enhancement In H-rassupporting

confidence: 89%

“…Accordingly, synapsin I/II double mutants show synaptic and learning deficits absent in either single gene mutant (Rosahl et al, 1995;Silva et al, 1996). Consistent with these findings, both synapsin I and II are required for an ERK-dependent facilitation of synaptosomal neurotransmitter release (Jovanovic et al, 2000).…”

Section: Figure 8 Ltp Enhancement In H-rassupporting

confidence: 63%

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Modulation of Presynaptic Plasticity and Learning by the H-ras/Extracellular Signal-Regulated Kinase/Synapsin I Signaling Pathway

Kushner¹,

Elgersma²,

Murphy³

et al. 2005

J. Neurosci.

170

162

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G12V), which is abundantly localized in axon terminals, we were able to increase the ERK-dependent phosphorylation of synapsin I. This resulted in several presynaptic changes, including a higher density of docked neurotransmitter vesicles in glutamatergic terminals, an increased frequency of miniature EPSCs, and increased paired-pulse facilitation. In addition, we observed facilitated neurotransmitter release selectively during high-frequency activity with consequent increases in long-term potentiation. Moreover, these mice showed dramatic enhancements in hippocampus-dependent learning. Importantly, deletion of synapsin I, an exclusively presynaptic protein, blocked the enhancements of learning, presynaptic plasticity, and long-term potentiation. Together with previous invertebrate studies, these results demonstrate that presynaptic plasticity represents an important evolutionarily conserved mechanism for modulating learning and memory.

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Section: Figure 8 Ltp Enhancement In H-rassupporting

confidence: 89%

Section: Figure 8 Ltp Enhancement In H-rassupporting

confidence: 63%

Modulation of Presynaptic Plasticity and Learning by the H-ras/Extracellular Signal-Regulated Kinase/Synapsin I Signaling Pathway

Kushner¹,

Elgersma²,

Murphy³

et al. 2005

J. Neurosci.

170

162

View full text Add to dashboard Cite

show abstract

“…CAMKII mRNA expression has been shown to be increased in dentate gyrus (molecular and granule cell layers) following perforant path LTP (Roberts et al, 1998) and increased in CA1 following Schaffer collateral induced LTP (Liu et al, 1999). Interestingly, mice with a mutant CAMKII show alterations in the frequency dependence of LTP induction (Hinds et al, 1998) together with deficits in spatial memory (Silva et al, 1996). The decrease found here was confined to the dentate gyrus and is perhaps indicative of reduced excitatory synaptic activity in this region either in excitatory inputs from the entorhinal cortex via the perforant path or outputs via synapses between mossy fibers and CA3 apical dendrites.…”

Section: Corticosterone-induced Changes In Hippocampal Expression Of mentioning

confidence: 99%

Flattening the Glucocorticoid Rhythm causes Changes in Hippocampal Expression of Messenger RNAs Coding Structural and Functional Proteins: Implications for Aging and Depression

Gartside

Leitch

McQuade

et al. 2002

Neuropsychopharmacol

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Subtle changes in glucocorticoid levels, including a flattening of the diurnal rhythm with raised nadir, are prevalent, being characteristic of both aging and major depression. Both these conditions are also associated with deficits in hippocampally mediated cognitive functions. We hypothesized that this profile of glucocorticoid levels causes structural and functional changes in the hippocampus, which in turn may engender cognitive deficits. We implanted slow-release corticosterone pellets into adrenally intact adult male rats to produce a flattened glucocorticoid rhythm with levels clamped midway between the normal nadir and zenith. Using density profile analysis we measured hippocampal expression of messenger RNAs encoding structural and functional proteins. In rats with a flattened glucocorticoid rhythm, the expression of the mRNA coding for microtubule associated protein-2b (MAP2b) was reduced in CA3 relative to sham-operated controls, but unchanged in dentate gyrus and CA1. In contrast, the expression of the mRNA coding the alpha subunit of calciumcalmodulin dependent kinase (CAMKIIa) was reduced in dentate gyrus in animals with a flattened glucocorticoid rhythm, but unchanged in CA3. The expression of the mRNA coding the synaptic vesicle protein synaptophysin was unchanged in both CA3 and dentate gyrus. The data indicate that a flattening of the normal diurnal glucocorticoid rhythm decreases the hippocampal expression of mRNAs coding key structural and functional proteins, and does so in a regionally selective manner. The data may have relevance for cognitive deficits characteristic of aging and depression.

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“…Both adult and larval Drosophila lacking Synapsin show associative memory scores that are reduced by about half as compared with wild-type animals, as do animals upon an RNAi-mediated knockdown of Synapsin (adult odor-punishment memory: Godenschwege et al 2004;Knapek et al 2010;Niewalda et al 2015;Walkinshaw et al 2015; larval odor-reward memory: Michels et al 2005Michels et al , 2011. Corresponding phenotypes in learning and memory tasks have been reported throughout the animal kingdom, including man (Silva et al 1996;Garcia et al 2004;Südhof, 2004;Gitler et al 2008;Greco et al 2013). …”

mentioning

confidence: 90%

Synapsin is required to “boost” memory strength for highly salient events

et al. 2015

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Synapsin is an evolutionarily conserved presynaptic phosphoprotein. It is encoded by only one gene in the Drosophila genome and is expressed throughout the nervous system. It regulates the balance between reserve and releasable vesicles, is required to maintain transmission upon heavy demand, and is essential for proper memory function at the behavioral level. Task-relevant sensorimotor functions, however, remain intact in the absence of Synapsin. Using an odor-sugar reward associative learning paradigm in larval Drosophila, we show that memory scores in mutants lacking Synapsin (syn 97 ) are lower than in wild-type animals only when more salient, higher concentrations of odor or of the sugar reward are used. Furthermore, we show that Synapsin is selectively required for larval short-term memory. Thus, without Synapsin Drosophila larvae can learn and remember, but Synapsin is required to form memories that match in strength to event salience-in particular to a high saliency of odors, of rewards, or the salient recency of an event. We further show that the residual memory scores upon a lack of Synapsin are not further decreased by an additional lack of the Sap47 protein. In combination with mass spectrometry data showing an up-regulated phosphorylation of Synapsin in the larval nervous system upon a lack of Sap47, this is suggestive of a functional interdependence of Synapsin and Sap47.

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Impaired learning in mice with abnormal short-lived plasticity

Cited by 163 publications

References 41 publications

Modulation of Presynaptic Plasticity and Learning by the H-ras/Extracellular Signal-Regulated Kinase/Synapsin I Signaling Pathway

Modulation of Presynaptic Plasticity and Learning by the H-ras/Extracellular Signal-Regulated Kinase/Synapsin I Signaling Pathway

Flattening the Glucocorticoid Rhythm causes Changes in Hippocampal Expression of Messenger RNAs Coding Structural and Functional Proteins: Implications for Aging and Depression

Synapsin is required to “boost” memory strength for highly salient events

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