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Autor     Sreedharan Sajikumar
Titel    Functional plasticity in the hippocampal slices in vitro
Jahr    2005
Anmerkung    Otto-von-Guericke-Universität Magdeburg, Diss., (rer.nat.), eingereicht am 03.12.2004, Verteidigung am 04.05.2005; S. 2: "I am thankful to Dr.Sajikumar Sreedharan and [...] for their encouragement and support during the initial period of my work."
URL    http://edoc.bibliothek.uni-halle.de/servlets/MCRFileNodeServlet/HALCoRe_derivate_00002188/sresajikumar.pdf

Literaturverz.   

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Fragmente    6


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[1.] Br/Fragment 011 21 - Diskussion
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The hippocampus has direct connections to the entorhinal cortex via the subiculum. Outputs from these structures can affect many other areas of the brain. For example the entorhinal cortex projects to the cingulated cortex, which has connections to the temporal lobe cortex, orbital cortex, and olfactory bulb. Thus, all of these areas can be influenced by hippocampal output, primarily from CA1. It has direct connections to the entorhinal cortex (via the subiculum) and the amygdala. Outputs from these structures can then affect many other areas of the brain (Fig. 1). For example, the entorhinal cortex projects to the cingulate cortex, which has a connection to the temporal lobe cortex, orbital cortex, and olfactory bulb. Thus, all of these areas can be influenced by hippocampal output, primarily from CA1.
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[2.] Br/Fragment 012 01 - Diskussion
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[The entorhinal cortex is a] major source of inputs to the hippocampus collecting information from the cingulated cortex, amygdale, orbital cortex and olfactory bulb (Johnson and Amaral, 1998). The hippocampus receives inputs via the precommissural branch of the fornix from the septal nuclei.

• Johnson D, Amaral D.G (1998) Hippocampus. In: G.M. Shepherd, Editor, The synaptic organization of the brain (4th ed.) Oxford University Press, Oxford. pp. 417–45.

The entorhinal cortex has a major source of inputs to the hippocampus, collecting information from the cingulate cortex, temporal lobe cortex, amygdala, orbital cortex, and olfactory bulb (Amaral and Witter, 1989). The hippocampus receives inputs via the precommissural branch of the fornix from the septal nuclei.

Amaral DG, Witter MP (1989) The three-dimensional organization of the hippocampal formation: a review of anatomical data. Neuroscience 31: 571-591.

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[3.] Br/Fragment 017 17 - Diskussion
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The hippocampal slice offers a variety of opportunities like visual control of electrode placement, possibility to direct electrodes to known parts of a given cell. For example an electrode may be placed in the apical or basal dendritic tree of pyramidal cells at known distances from the soma to record the activity of a small population of synapses. Furthermore in the slice preparation, the ability to change the concentration of interesting molecules at will provides a good experimental control of the preparation. In addition to the temperature and oxygen concentration, the pH, ionic concentration and hormonal levels can be changed at will. Brain slices offer a variety of novel opportunities, the most obvious being visual inspection. [...] This allows visual control of electrode placement. It is also possible to direct electrodes to known parts of a given cell. For example, in the hippocampus, an electrode may be placed in the apical or basal dendritic tree of pyramidal cells at known distances from the soma to record the activity of a small group of synapses. [...] Furthermore, in the slice preparation the influence of the blood brain barrier is removed. The ability to change the tissue concentration of interesting molecules at will provides good experimental control of the preparation. In addition to the temperature and oxygen concentration, the pH, ionic concentration and hormonal levels can be changed at will.
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[4.] Br/Fragment 018 04 - Diskussion
Zuletzt bearbeitet: 2016-05-21 18:17:28 Schumann
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1.3.1. Properties of LTP

As a result of brief high frequency stimulation, the LTP expressed in CA3-CA1 synapse of hippocampal region show some basic properties such as ‘inputspecificity’, ‘co-operativity’, ‘associativity’ and ‘late-associativity’ (Bear and Malenka, 1994; Bliss and Collingridge, 1993; Frey and Morris, 1997, 1998; Malenka and Bear, 2004). LTP is input-specific in general, which means those synapses who receive high frequency stimulation only will express LTP. This property of LTP is consistent with its involvement in memory formation. If the activation of one set of synapses leads to the simultaneous activation of all other synapses, even inactive ones, being potentiated, it would be difficult to activate selectively a particular sets of inputs, as is presumably required for learning and memory (Bliss and Collingridge, 1993).


• Bear MF, Malenka RC (1994) Synaptic plasticity: LTP and LTD. Curr Opin Neurobiol 4:38 9[sic]-399.

• Bliss TV, Collingridge GL (1993) A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361:31-39.

• Frey U, Morris RGM (1997) Synaptic tagging and long-term potentiation. Nature 385:533-536.

• Frey U, Morris RGM (1998a) Synaptic tagging: implications for latemaintenance of hippocampal long-term potentiation. Trends Neurosci 21:181-188.

• Frey U, Morris RGM (1998b) Weak before strong: dissociating synaptic tagging and plasticity-factor accounts for late-LTP. Neuropharmacology 37:545-552.

• Malenka RC and Bear MF (2004) LTP and LTD: an embarrassment of riches. Neuron 44:5-21.

1.4. Basic properties of LTP and LTD

LTP and LTD at the Schaffer collaterals CA1 synapses share several common properties: like input-specificity, co-operativity, associativity and late-associativity (Bliss and Collingridge, 1993;Bear and Malenka, 1994;Malenka and Bear, 2004). LTP/LTD is input-specific, in the sense that it is restricted to the synapses which receive high-frequency stimulation (HFS) or low-frequency stimulation respectively (LFS) (Kelso and Brown, 1986;Lynch et al., 1977). This feature is consistent with its involvement in memory formation. If activation of one set of synapses led to the activation of all other synapses, even inactive ones-being potentiated or depressed, it would be difficult to selectively enhance particular sets of inputs, as is presumably required for learning and memory (Bliss and Collingridge, 1993).


Bear MF, Malenka RC (1994) Synaptic plasticity: LTP and LTD. Curr Opin Neurobiol 4: 389-399.

Bliss TV, Collingridge GL (1993) A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361: 31-39.

Kelso SR, Brown TH (1986) Differential conditioning of associative synaptic enhancement in hippocampal brain slices. Science 232: 85-87.

Lynch GS, Dunwiddie T, Gribkoff V (1977) Heterosynaptic depression: a postsynaptic correlate of long-term potentiation. Nature 266: 737-739.

Malenka RC, Bear MF (2004) LTP and LTD; An Embarrassment of Riches. Neuron 44: 5-21.

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[5.] Br/Fragment 018 20 - Diskussion
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This selective enhancement of conjointly activated synaptic inputs is often considered as a cellular analog correlate of associative or classical conditioning. Otherways, associativity is expected in any network of neurons that links one set information with another. ‘Late-associativity’ is a novel property of LTP, which describes intersynaptic interventions within a time frame of few minutes to few hours (Frey and Morris, 1997, 1998a, 1998b). More clearly, a weak protein synthesis-independent early-LTP in one synaptic input can be [transformed into a late, protein synthesis-dependent form, if a protein synthesis-dependent late-LTP is induced in the second synaptic input preceded by the weak events in the first synaptic input (“Weak before strong”) within a specific time frame (Frey and Morris, 1998a, 1998b; Frey , 2001 ; Frey and Frey, 2008; Kauderer and Kandel, 2000; Sajikumar and Frey, 2004a).]

• Frey U, Frey S, Schollmeier F, Krug M (1995) Influence of actinomycin D, a RNA synthesis inhibitor, on long-term potentiation in rat hippocampal neurons in vivo and in vitro. J Physiol 490:703-711

• Frey U, Morris RGM (1997) Synaptic tagging and long-term potentiation. Nature 385:533-536.

• Frey U, Morris RGM (1998a) Synaptic tagging: implications for late maintenance of hippocampal long-term potentiation. Trends Neurosci 21:181-188.

• Frey U, Morris RGM (1998b) Weak before strong: dissociating synaptic tagging and plasticity-factor accounts for late-LTP. Neuropharmacology 37:545-552.

• Frey S, Bergado-Rosado J, Seidenbecher T, Pape HC, Frey JU (2001) Reinforcement of early long-term potentiation (early-LTP) in dentate gyrus by stimulation of the basolateral amygdala: heterosynaptic induction mechanisms of late-LTP. J Neurosci 21:3697-3703.

• Kauderer BS, Kandel ER (2000) Capture of a protein synthesis-dependent component of long-term depression. Proc Natl Acad Sci U S A.97:13342-7.

• Sajikumar S, Frey JU (2004) Resetting of synaptic tags is time-and activity-dependent in rat hippocampal CA1 in vitro. Neuroscience 129:503-507.

• Sajikumar S, Frey JU (2004) Late-associativity, synaptic tagging, and the role of dopamine during LTP and LTD. Neurobiol Learn Mem 82:12-25.

This selective enhancement /depression of conjointly activated sets of synaptic inputs is often considered as a cellular analog of associative or classical conditioning. More generally, associativity is expected in any network of neurons that links one set of information with another.

Late-associativity is a novel property of LTP/LTD. It describes intersynaptic interventions within a time frame of few minutes to few hours (Frey and Morris, 1997;Frey and Morris, 1998a;Frey and Morris, 1998b;Morris and Frey, 1999). More clearly, a weak protein synthesis independent early-LTP/-LTD in one synaptic input can be transformed into a late, protein synthesis-dependent form, if a protein synthesis-dependent late-LTP/-LTD is induced in the second synaptic input preceded by the weak events in the first synaptic input (weak before strong) within a specific time frame (Frey and Morris, 1998b;Kauderer and Kandel, 2000).


Frey U, Morris RG (1997) Synaptic tagging and long-term potentiation. Nature 385: 533-536.

Frey U, Morris RG (1998a) Synaptic tagging: implications for late maintenance of hippocampal long-term potentiation. Trends Neurosci 21: 181-188.

Frey U, Morris RG (1998b) Weak before strong: dissociating synaptic tagging and plasticity-factor accounts of late-LTP. Neuropharmacology 37: 545-552.

Kauderer BS, Kandel ER (2000) Capture of a protein synthesis-dependent component of long-term depression. Proc Natl Acad Sci U S A 97: 13342-13347.

Morris RG, Frey U (1999) Tagging the hebb synapse: reply. Trends Neurosci 22: 256.

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[6.] Br/Fragment 021 21 - Diskussion
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Because the NMDA receptors are sensitive to both presynaptic transmitter release and postsynaptic depolarization; they act as Hebbian coincidence detectors (Collingridge, 2003). NMDA-receptor-dependent LTP can be triggered experimentally either by delivering high-frequency trains to a critical number of presynaptic afferents, or by [pairing postsynaptic depolarization with pre-synaptic stimulation (Wigstrom [sic] and Gustafsson, 1986).]

• Collingridge G (2003) The induction of N-methyl-D-aspartate receptordependent long-term potentiation. Philos Trans R Soc Lond B Biol Sci 358:635-41.

• Wigström H, Gustafsson B (1986) Postsynaptic control of hippocampal longterm potentiation. J Physiol (Paris) 81:228-36.

Because NMDA-receptors are sensitive to both presynaptic transmitter release and postsynaptic depolarization, they act as Hebbian coincidence detectors (Collingridge, 2003). NMDA-receptor- dependent LTP can be triggered experimentally either by delivering high-frequency tetani to a critical number of presynaptic afferent fibers, or by pairing postsynaptic depolarization with presynaptic stimulation (Gustafsson et al., 1987).

Collingridge GL (2003) The induction of N-methyl-D-aspartate receptor-dependent long-term potentiation. Philos Trans R Soc Lond B Biol Sci 358: 635-641.

Gustafsson B, Wigstrom H, Abraham WC, Huang YY (1987) Long-term potentiation in the hippocampus using depolarizing current pulses as the conditioning stimulus to single volley synaptic potentials. J Neurosci 7: 774-780.

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Though nearly identical nothing has been marked as a citation.

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