P Andersen

University of Oslo, Oslo, Oslo, Norway

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Publications (62)436.24 Total impact

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    ABSTRACT: Cells in nucleus ventralis posterolateralis thalami, lateral to the relay cells of the hindlimb component of the dorsal column pathway, have been studied with extra-and intracellular recordings in cats anaesthetized with pentobarbital sodium. The cells in this part of thalamus are characterized by a considerable convergence, many cells being excited from the hindlimb component of the spinocervico-lemniscal (SCLT) and the dorsal column (DC) pathways as well as from forelimb nerves. The synaptic action of an afferent volley was strong, and large unitary EPSPs were frequently observed, particularly when the SCLT was stimulated. Many of the cells were relay cells and could be antidromically invaded from the ipsilateral cortical areas S I and S II. A number of cells were antidromically invaded from both S I and S II, indicating that these cells project to cortex with a divided axon. Many cells showed an inhibition of the recurrent type.
    Acta Physiologica Scandinavica 12/2008; 68(1):72 - 83. · 2.55 Impact Factor
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    ABSTRACT: The membrane potential changes following action potentials in thin unmyelinated cortical axons with en passant boutons may be important for synaptic release and conduction abilities of such axons. In the lack of intra-axonal recording techniques we have used extracellular excitability testing as an indirect measure of the after-potentials. We recorded from individual CA3 soma in hippocampal slices and activated the axon with a range of stimulus intensities. When conditioning and test stimuli were given to the same site the excitability changes were partly masked by local effects of the stimulating electrode at intervals < 5 ms. Therefore, we elicited the conditioning action potential from one axonal branch and tested the excitability of another branch. We found that a single action potential reduced the axonal excitability for 15 ms followed by an increased excitability for approximately 200 ms at 24 degrees C. Using field recordings of axonal action potentials we show that raising the temperature to 34 degrees C reduced the magnitude and duration of the initial depression. However, the duration of the increased excitability was very similar (time constant 135 +/- 20 ms) at 24 and 34 degrees C, and with 2.0 and 0.5 mM Ca2+ in the bath. At stimulus rates > 1 Hz, a condition that activates a hyperpolarization-activated current (Ih) in these axons, the decay was faster than at lower stimulation rates. This effect was reduced by the Ih blocker ZD7288. These data suggest that the decay time course of the action potential-induced hyperexcitability is determined by the membrane time constant.
    The Journal of Physiology 10/2004; 560(Pt 2):491-503. · 4.38 Impact Factor
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    ABSTRACT: In adult mice, long-term potentiation (LTP) of synaptic transmission at CA3-to-CA1 synapses induced by tetanic stimulation requires L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors containing GluR-A subunits. Here, we report a GluR-A-independent form of LTP, which is comparable in size to LTP in wild-type mice at postnatal day 14 (P14) but diminishes between P14 and P42 in brain slices of GluR-A-deficient mice. The GluR-A-independent form of LTP is sensitive to D(-)-2-amino-5-phosphonopentanoic acid (D-AP5), but lacks short-term potentiation (STP) and can also be observed in the pairing induction protocol. As judged by unaltered paired-pulse facilitation, this LTP form is postsynaptically expressed despite depleted extrasynaptic AMPA receptor pools with reduced levels of GluR-B, which accumulates in somata and synapses of CA1 pyramidal neurons in GluR-A-deficient mice. Our results show that in the developing hippocampus synaptic plasticity can be expressed by AMPA receptors lacking the GluR-A subunit.
    The Journal of Physiology 01/2004; 553(Pt 3):843-56. · 4.38 Impact Factor
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    Per Andersen
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    ABSTRACT: Searching for premonitory studies of hippocampal long-term potentiation (LTP), there is a paucity of data. While synaptic enhancement during repetitive activation was studied in several reports from many groups between 1955 and 1967, the reported after-effects were short, at the most lasting a few minutes. Responses lasting for more than 1 hour were not reported until 1973.
    Philosophical Transactions of The Royal Society B Biological Sciences 05/2003; 358(1432):613-5. · 6.23 Impact Factor
  • Anne F Soleng, Morten Raastad, Per Andersen
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    ABSTRACT: Relatively few physiological studies have been carried out on intrahippocampal axons. We have recorded compound potentials from fiber groups and the activity of individual axons at 22-25 degrees C to characterize the conduction in subsets of the broad fan-shaped CA3 pyramidal axonal tree, including the Schaffer collaterals and longitudinal branches. The same wide axonal branching was indicated by antidromic activation of individual CA3 pyramidal cells. The average compound action potential latency from the CA3 to the CA1 area (Schaffer collaterals) increased by 4.16 +/- 0.06 ms/mm separation between the stimulation and registration electrodes. The impulses spread 31% faster in the 45-degree oblique temporal than in the transverse direction across CA1. The latency of the longitudinal axons in the CA3 area increased by 6.19 +/- 0.19 ms/mm. More impressive than these direction-dependent differences in latency were the large differences between individual axons running in the same direction. For both the longitudinal axons and the Schaffer collaterals, there was a broad distribution of antidromic latencies for a given distance between the stimulation and recording points. Typically, the fastest impulses arrived in half the time of the slowest. The distribution of compound action potential latencies between two points in the tissue could be made narrower by surgical restriction of the thickness and width of the preparation. By comparison, the cerebellar parallel fibers showed a narrower distribution of their latencies than the Schaffer collaterals. Because the cerebellar fibers run more straight than Schaffer collaterals, this suggested that some of the latency differences of the latter were due to differences in the path length of the axons. One consequence of our findings is that synchronous firing of neighboring CA3 pyramidal cells does not necessarily give synchronous inputs to common target CA1 neurons.
    Hippocampus 02/2003; 13(8):953-61. · 5.49 Impact Factor
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    ABSTRACT: Along unmyelinated central axons, synapses occur at focal swellings called axonal varicosities (boutons). The mechanisms regulating how frequently synapses and varicosities occur along axons remain poorly understood. Here, to investigate varicosity distribution patterns and the extent to which they may be conserved across different axons, we analyzed varicosity numbers and positions along fluorescently labeled axon branches in hippocampal area CA1 (CA3-to-CA1 "Schaffer collateral" axons) and five other synaptic regions of rat hippocampus and cerebellum. Varicosity spacing varied by region; e.g., 3.7 +/- 0.6 microm (mean +/- SD) for CA3-to-CA1 axons and 5.2 +/- 1.0 microm for cerebellar parallel fibers. Surprisingly, when 56 axons from these different regions were pooled into a single heterogeneous group, a general relationship emerged: the spacing variability (SD) was a constant fraction of the mean spacing, suggesting that varicosities along different axons are distributed in a fundamentally similar, scaled manner. Varicosity spacing was neither regular nor random but followed a pattern consistent with random synaptic distributions and the occurrence of multiple-synapse boutons. A quantitative model reproduced the salient features of the data and distinguished between two proposed mechanisms relating axonal morphogenesis and synaptogenesis.
    Proceedings of the National Academy of Sciences 05/2002; 99(9):6340-5. · 9.81 Impact Factor
  • P Andersen, A F Soleng, M Raastad
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    ABSTRACT: We have re-examined the hippocampal lamellar organization of the CA3-to-CA1 connection. Based on a new technique with electrophysiological quantification of Schaffer collateral density, and a review of recent literature, we conclude that the lamellar organization remains a useful concept for understanding hippocampal connectivity. Using a sheet-like hippocampal preparation, containing the whole CA1 region, we mapped the distribution of Schaffer collaterals by two procedures. First, we recorded the amplitude of the Schaffer compound action potential in various parts of CA1 after stimulation of a point in CA3. Second, we charted the CA1 positions from which we could antidromically excite individual CA3 neurones. Although the Schaffer collaterals radiated from their CA3 cells of origin within a wide, fan-shaped area, covering a large part of the septo-temporal extent of CA1, the amplitude of the compound action potential was largest in a slightly oblique, transverse band across the CA1 towards the subicular region.
    Brain Research 01/2001; 886(1-2):165-171. · 2.88 Impact Factor
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    M Segal, P Andersen
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    ABSTRACT: A recent series of exciting observations, using novel high-resolution time-lapse imaging of living cells, has provoked a major shift in our understanding of the dendritic spine, from a stable storage site of long-term memory to a dynamic structure that undergoes rapid morphological variations. Through these recent observations, the molecular mechanisms underlying spine plasticity are beginning to emerge. A common mechanism involving changes in intracellular Ca(2+) concentration may control both the formation/elongation and the pruning/retraction of spines. Spine motility may be instrumental in the formation of synapses, may contribute to the anchoring/removing of glutamate receptors at spine heads, and may control the efficacy of existing synapses.
    Current Opinion in Neurobiology 11/2000; 10(5):582-6. · 7.34 Impact Factor
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    ABSTRACT: Protein phosphatase inhibitor-1 (I-1) has been proposed as a regulatory element in the signal transduction cascade that couples postsynaptic calcium influx to long-term changes in synaptic strength. We have evaluated this model using mice lacking I-1. Recordings made in slices prepared from mutant animals and also in anesthetized mutant animals indicated that long-term potentiation (LTP) is deficient at perforant path-dentate granule cell synapses. In vitro, this deficit was restricted to synapses of the lateral perforant path. LTP at Schaffer collateral-CA1 pyramidal cell synapses remained normal. Thus, protein phosphatase-1-mediated regulation of NMDA receptor-dependent synaptic plasticity involves heterogeneous molecular mechanisms, in both different dendritic subregions and different neuronal subtypes. Examination of the performance of I-1 mutants in spatial learning tests indicated that intact LTP at lateral perforant path-granule cell synapses is either redundant or is not involved in this form of learning.
    Journal of Neuroscience 06/2000; 20(10):3537-43. · 6.91 Impact Factor
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    ABSTRACT: We have re-examined the hippocampal lamellar organization of the CA3-to-CA1 connection. Based on a new technique with electrophysiological quantification of Schaffer collateral density, and a review of recent literature, we conclude that the lamellar organization remains a useful concept for understanding hippocampal connectivity. Using a sheet-like hippocampal preparation, containing the whole CA1 region, we mapped the distribution of Schaffer collaterals by two procedures. First, we recorded the amplitude of the Schaffer compound action potential in various parts of CA1 after stimulation of a point in CA3. Second, we charted the CA1 positions from which we could antidromically excite individual CA3 neurones. Although the Schaffer collaterals radiated from their CA3 cells of origin within a wide, fan-shaped area, covering a large part of the septo-temporal extent of CA1, the amplitude of the compound action potential was largest in a slightly oblique, transverse band across the CA1 towards the subicular region.
    Brain Research - BRAIN RES. 01/2000; 886(1):165-171.
  • P Andersen
    Brain Research Bulletin 11/1999; 50(5-6):305-6. · 2.94 Impact Factor
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    ABSTRACT: Gene-targeted mice lacking the L-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor subunit GluR-A exhibited normal development, life expectancy, and fine structure of neuronal dendrites and synapses. In hippocampal CA1 pyramidal neurons, GluR-A-/- mice showed a reduction in functional AMPA receptors, with the remaining receptors preferentially targeted to synapses. Thus, the CA1 soma-patch currents were strongly reduced, but glutamatergic synaptic currents were unaltered; and evoked dendritic and spinous Ca2+ transients, Ca2+-dependent gene activation, and hippocampal field potentials were as in the wild type. In adult GluR-A-/- mice, associative long-term potentiation (LTP) was absent in CA3 to CA1 synapses, but spatial learning in the water maze was not impaired. The results suggest that CA1 hippocampal LTP is controlled by the number or subunit composition of AMPA receptors and show a dichotomy between LTP in CA1 and acquisition of spatial memory.
    Science 07/1999; 284(5421):1805-11. · 31.03 Impact Factor
  • P Andersen
    Nature 06/1999; 399(6731):19-21. · 38.60 Impact Factor
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    P Andersen, A F Soleng
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    ABSTRACT: Most central excitatory synapses occur on dendritic spines. A new study shows that spine stability depends on spontaneous glutamate release and AMPA receptors.
    Nature Neuroscience 02/1999; 2(1):5-7. · 15.25 Impact Factor
  • P Andersen
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    ABSTRACT: Recently, we have witnessed considerable progress in the field of memory research. New approaches and techniques have allowed the fractionation of memory in several subentities. Working memory, in which sensory information is manipulated for 10-20 seconds, is served by an area laterally in the frontal lobes. Long-lasting memories are either of the explicit or implicit variety. Contents of explicit memory stores can be accessed by conscious processes and depend upon medial temporal lobe structures, in particular the hippocampal formation. Implicit memories can not be consciously accessed and have its many substrates distributed to different parts of the brain, depending upon the material or procedures involved. Long-term memories are reconstructive and thus amenable to forgetting, alteration and, in some cases, even repression.
    Tidsskrift for Den norske legeforening 01/1999; 118(30):4729-35.
  • P Andersen, A F Soleng
    Brain Research Reviews 06/1998; 26(2-3):353-9. · 7.82 Impact Factor
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    ABSTRACT: NMDA receptors, a class of glutamate-gated cation channels with high Ca2+ conductance, mediate fast transmission and plasticity of central excitatory synapses. We show here that gene-targeted mice expressing NMDA receptors without the large intracellular C-terminal domain of any one of three NR2 subunits phenotypically resemble mice made deficient in that particular subunit. Mice expressing the NR2B subunit in a C-terminally truncated form (NR2B(deltaC/deltaC) mice) die perinatally. NR2A(deltaC/deltaC) mice are viable but exhibit impaired synaptic plasticity and contextual memory. These and NR2C(deltaC/deltaC) mice display deficits in motor coordination. C-terminal truncation of NR2 subunits does not interfere with the formation of gateable receptor channels that can be synaptically activated. Thus, the phenotypes of our mutants appear to reflect defective intracellular signaling.
    Cell 02/1998; 92(2):279-89. · 31.96 Impact Factor
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    ABSTRACT: The hippocampus is critically involved in spatial learning. Spatial training in adult rats, which improved their spatial learning ability, increased the number of excitatory hippocampal CA1 spine synapses on basal dendrites as compared with either isolated or standardly housed animals (Moser et al. [1994] Proc. Natl. Acad. Sci. USA 91:12673-12675). In this article, we report that spine synapses on oblique apical dendritic branches do not increase in density or number after the same type of training. When examining the variability of the spine density on basal CA1 dendrites by using variance component analysis, the variance associated with the cells was twice as large in all three groups as that coupled to the rats. Analysis of the spine density plots shows that the enhanced spine density after spatial training is found in most cells recorded from the trained group but that a small subset of CA1 neurones are particularly well supplied with spines. The trained group had a significant right-skewed tail of the spine distribution, i.e., training caused high spine density to occur in a small subset of dendritic segments. Conversely, the isolated group had a significant left-skewed spine distribution, indicating that some of the dendritic segments were undersupplied with spines, whereas the paired group displayed no asymmetry.
    The Journal of Comparative Neurology 05/1997; 380(3):373-81. · 3.66 Impact Factor
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    ABSTRACT: The hippocampus is critically involved in spatial learning. Spatial training in adult rats, which improved their spatial learning ability, increased the number of excitatory hippocampal CA1 spine synapses on basal dendrites as compared with either isolated or standardly housed animals (Moser et al. [1994] Proc. Natl. Acad. Sci. USA 91:12673–12675). In this article, we report that spine synapses on oblique apical dendritic branches do not increase in density or number after the same type of training. When examining the variability of the spine density on basal CA1 dendrites by using variance component analysis, the variance associated with the cells was twice as large in all three groups as that coupled to the rats. Analysis of the spine density plots shows that the enhanced spine density after spatial training is found in most cells recorded from the trained group but that a small subset of CA1 neurones are particularly well supplied with spines. The trained group had a significant right-skewed tail of the spine distribution, i.e., training caused high spine density to occur in a small subset of dendritic segments. Conversely, the isolated group had a significant left-skewed spine distribution, indicating that some of the dendritic segments were undersupplied with spines, whereas the paired group displayed no asymmetry. J. Comp. Neurol. 380:373–381, 1997. © 1997 Wiley-Liss, Inc.
    The Journal of Comparative Neurology 04/1997; 380(3):373 - 381. · 3.66 Impact Factor
  • P Andersen, E Moser, M B Moser, M Trommald
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    ABSTRACT: Learning through exploration gives increased synaptic field potentials in the perforant path/dentate synapses, largely due to an activity-dependent brain temperature increase. After temperature compensation, spatial learning was associated with small, but significant, STP-like changes of the field potential lasting 20-30 min. A group of spatially trained adult rats showed faster spatial learning and about 10% higher basal dendritic spine density (LY-filled) compared to two control groups. With unchanged dendritic length and branching pattern, the results suggest the formation of new synapses.
    Journal of Physiology-Paris 02/1996; 90(5-6):349. · 0.82 Impact Factor

Publication Stats

4k Citations
436.24 Total Impact Points

Institutions

  • 1967–2003
    • University of Oslo
      • • Department of Physiology
      • • Institute of Basic Medical Sciences
      Oslo, Oslo, Norway
  • 2000
    • Weizmann Institute of Science
      • Department of Neurobiology
      Israel