| 1. |
- Abrahamsson, Therése, 1976, et al.
(författare)
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AMPA silencing is a prerequisite for developmental long-term potentiation in the hippocampal CA1 region.
- 2008
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Ingår i: Journal of neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598.
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Tidskriftsartikel (refereegranskat)abstract
- AMPA unsilencing is an often proposed expression mechanism both for developmental LTP, involved in circuitry refinement during brain development, and for mature LTP, involved in learning and memory. In the hippocampal CA3-CA1 connection naïve (non-stimulated) synapses are AMPA-signaling, and AMPA-silent synapses are created from naïve AMPA-signaling (AMPA-labile) synapses by test pulse synaptic activation (AMPA silencing). To investigate to what extent LTP at different developmental stages are explained by AMPA unsilencing, the amount of LTP obtained at these different developmental stages was related to the amount of AMPA silencing that preceded the induction of LTP. When examined in the second postnatal week Hebbian induction was found to produce no more stable potentiation than that causing a return to the naïve synaptic strength existing prior to the AMPA silencing. Moreover, in the absence of a preceding AMPA silencing Hebbian induction produced no stable potentiation above the naïve synaptic strength. Thus, this early, or developmental, LTP is nothing more than an unsilencing (de-depression), and stabilization, of the AMPA signaling that was lost by the prior AMPA silencing. This de-depression and stabilization of AMPA signaling was mimicked by the presence of the PKA-activator forskolin. As the relative degree of AMPA silencing decreased with development, LTP manifested itself more and more as a "genuine" potentiation (as opposed to a de-depression) not explained by unsilencing and stabilization of AMPA-labile synapses. This "genuine", or mature, LTP rose from close to nothing of total LTP prior to P13, to about 70 % of total LTP at P16, and to about 90 % of total LTP at P30. Developmental LTP, by stabilization of AMPA labile synapses, thus seems adapted to select synaptic connections to the growing synaptic network. Mature LTP, by instead strengthening existing stable connections between cells, may then create functionally tightly connected cell assemblies within this network.
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| 2. |
- Abrahamsson, Therése, 1976
(författare)
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Plasticity of the developing glutamate synapse in the hippocampus
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Synapses are highly plastic, i.e. they have the ability to change their signaling strength both in the short- and long-term (e.g. long-term potentiation - LTP) in response to specific patterns of activity. In the developing brain synaptic plasticity promotes activity-dependent development, whereas in the mature brain synaptic plasticity forms the basis for learning and memory. Although both development and learning involve organization and reorganization of synaptic circuits, the extent to which the plasticity behind these two phenomena uses the same mechanisms is unknown. The glutamate synapse which represents > 90 % of the brain synapses signals mainly via postsynaptic AMPA and NMDA receptors. In the developing brain, sparse synaptic activation can make the synapse lose its AMPA signaling capacity, i.e. make it AMPA silent, while LTP can reinstall the AMPA signaling (unsilencing). The aim of this study was to investigate the possible role of the AMPA silent synapse, and its unsilencing, in developmental and mature synaptic plasticity. Electrophysiological recordings of synaptic transmission in the CA1 region and in the dentate gyrus of acute hippocampal slices were used for these studies. A new and unexpected finding was that AMPA unsilencing can also be induced by not activating the AMPA silent synapse for tens of minutes. Together with previous findings this suggests a model in which the glutamate synapse is born with a single AMPA labile module, i.e. the synapse cycles between an AMPA silent state, induced by sparse synaptic activity, and an AMPA signaling state, induced by the absence of synaptic activity. The results further suggest that AMPA silencing is a prerequisite for developmental LTP to occur. In other words, developmental LTP does not potentiate synaptic transmission but rather stabilizes the AMPA labile module. It can, however, transiently potentiate the synapse by the addition of a labile AMPA module to an existing synapse with a single stable AMPA module. After this initial period of synaptic stabilization there is an increase in synaptic connectivity between pre- and postsynaptic neurons. It is proposed that this increased connectivity can be explained, at least partly, by the addition of stable AMPA modules to existing synapses promoted by mature LTP. This thesis thus proposes that, using the same principle mechanism, namely the addition of stable AMPA modules, developmental LTP promotes initial synaptic stabilization while mature LTP promotes synaptic growth.
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| 3. |
- Abrahamsson, Therése, 1976, et al.
(författare)
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Reversible synaptic depression in developing rat CA3-CA1 synapses explained by a novel cycle of AMPA silencing-unsilencing
- 2007
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Ingår i: JOURNAL OF NEUROPHYSIOLOGY. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 98:5, s. 2604-2611
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Tidskriftsartikel (refereegranskat)abstract
- In the developing hippocampus, experiments using whole cell recordings have shown that a small number of synaptic activations can convert many glutamate synapses to AMPA silent synapses. This depression of AMPA signaling is induced by low-frequency (0.05–0.2 Hz) activation, does not require N-methyl-d-aspartate or metabotropic glutamate receptor activation for its induction, and does not readily reverse after stimulus interruption. Here we show, using field recordings and perforated patch-clamp recordings of transmission in developing CA3–CA1 synapses, that this synaptic depression also can be observed under more noninvasive recording conditions. Moreover, under these conditions, the synaptic depression spontaneously recovers within 20 min by the absence of synaptic activation alone, with a time constant of ∼7 min as determined by field excitatory postsynaptic potential recordings. Thus as for the expression of long-term potentiation (LTP), recovery from this depression is susceptible to whole cell dialysis (“wash-out”). In contrast to LTP-induced unsilencing, the AMPA signaling after stimulus interruption was again labile, resumed stimulation resulted in renewed depression. The present study has thus identified a novel cycle for AMPA signaling in which the nascent glutamate synapse cycles between an AMPA silent state, induced by a small number of synaptic activations, and a labile AMPA signaling, induced by prolonged inactivity.
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| 4. |
- Abrahamsson, Therése, 1976, et al.
(författare)
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Synaptic fatigue at the naive perforant path-dentate granule cell synapse in the rat.
- 2005
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Ingår i: The Journal of physiology. - : Wiley. - 0022-3751. ; 569:Pt 3, s. 737-50
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Tidskriftsartikel (refereegranskat)abstract
- Synaptic activation at low frequency is often used to probe synaptic function and synaptic plasticity, but little is known about how such low-frequency activation itself affects synaptic transmission. In the present study, we have examined how the perforant path-dentate granule cell (PP-GC) synapse adapts to low-frequency activation from a previously non-activated (naive) state. Stimulation at 0.2 Hz in acute slices from developing rats (7-12 days old) caused a gradual depression of the AMPA EPSC (at -80 mV) to about half within 50 stimuli. This synaptic fatigue was unaffected by the NMDA and metabotropic glutamate (mGlu) receptor antagonists d-AP5 and LY-341495. A smaller component of this synaptic fatigue was readily reversible when switching to very low-frequency stimulation (0.033-0.017 Hz) and is attributed to a reversible decrease in release probability, which is probably due to depletion of readily releasable vesicles. Thus, it was expressed to the same extent by AMPA and NMDA EPSCs, and was associated with a decrease in quantal content (measured as 1/CV(2)) with no change in the paired-pulse ratio. The larger component of the synaptic fatigue was not readily reversible, was selective for AMPA EPSCs and was associated with a decrease in 1/CV(2), thus probably representing silencing of AMPA signalling in a subset of synapses. In adult rats (> 30 days old), the AMPA silencing had disappeared while the low-frequency depression remained unaltered. The present study has thus identified two forms of synaptic plasticity that contribute to fatigue of synaptic transmission at low frequencies at the developing PP-GC synapse; AMPA silencing and a low-frequency depression of release probability.
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| 5. |
- Ponten, Henrik, et al.
(författare)
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Behavioral and neurochemical repercussions of hippocampal network activity blockade during the neonatal period.
- 2005
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Ingår i: Brain research. Developmental brain research. - : Elsevier BV. - 0165-3806. ; 155:1, s. 81-6
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Tidskriftsartikel (refereegranskat)abstract
- Early destruction of the ventral hippocampus from postnatal day 7 (P7) has been shown to induce behavioral alterations in post-pubertal rats, similar to those observed in models for schizophrenia. Using a single injection of tetanus toxin into the ventral hippocampus at P1, we tested the consequences of an early neonatal activity deprivation (
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