| 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, 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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| 3. |
- Camitz, Martin, et al.
(författare)
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The effect of time distribution shape on a complex epidemic model
- 2009
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Ingår i: Bulletin of Mathematical Biology. - : Springer Science and Business Media LLC. - 0092-8240 .- 1522-9602. ; 71:8, s. 1902-1913
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Tidskriftsartikel (refereegranskat)abstract
- In elaborating a model of the progress of an epidemic, it is necessary to make assumptions about the distributions of latency times and infectious times. In many models, the often implicit assumption is that these times are independent and exponentially distributed. We explore the effects of altering the distribution of latency and infectious times in a complex epidemic model with regional divisions connected by a travel intensity matrix. We show a delay in spread with more realistic latency times. More realistic infectiousness times lead to faster epidemics. The effects are similar but accentuated when compared to a purely homogeneous mixing model.
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| 4. |
- Elbe, Jörgen, et al.
(författare)
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The destination-management organisation and the integrative destination-marketing process
- 2009
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Ingår i: The international journal of tourism research. - : Wiley. - 1099-2340 .- 1522-1970. ; 11:3, s. 283-296
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Tidskriftsartikel (refereegranskat)abstract
- A main function of destination-management organisations (DMOs) is that of being responsible for marketing their destinations. Many destinations involve stakeholders of different kinds. DMOs often have modest resources, and this creates a challenge: how should the DMO manage their marketing activities and achieve an outcome that benefits both the individual stakeholder and the destination? This study describes how DMOs can mobilise resources among the stakeholders and identifies the processes leading to integrated destination marketing. Basing our conclusions on a case study, we find that DMOs need to develop both pragmatic and moral legitimacy in order to develop integrated destination marketing.
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| 5. |
- Ogren, M., et al.
(författare)
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Prevalence and risk of pulmonary embolism in patients with intracardiac thrombosis: a population-based study of 23 796 consecutive autopsies
- 2005
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Ingår i: Eur Heart J. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 26:11, s. 1108-14
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: While right intracardiac thrombosis (IT) is a potential cause of pulmonary embolism (PE) similar to that of stroke in left-sided IT, its prevalence and prognostic significance has not been studied in the general population. The aim of this study was to assess the age- and gender-specific prevalence of IT and its relation to PE in a population-based autopsy cohort. METHODS AND RESULTS: Between 1970 and 1982, 23 796 autopsies, representing 84% of all in-hospital deaths in the Malmo city population, were performed, using a standardized procedure. The relationship between IT and PE was evaluated by cohort analyses and nested case-control studies. IT was present in 1706 (7.2%) patients, 727 and 747 of whom had right and left atrial IT, respectively. PE prevalence in patients with isolated left IT, isolated right IT, and combined IT was 28.5, 35.6, and 48.9%, with RR (95% CI) of 1.5 (1.3-1.8), 2.0 (1.6-2.5), and 3.5 (2.7-4.7), respectively, compared with age- and gender-matched controls. Patients dying from ischaemic heart disease had a 3.2 (2.7-3.6) times higher risk of right IT, which was associated with 43% PE prevalence. Of all patients with PE at autopsy, right IT was found in 354 (6.5%), and the only detected source of PE in 220 (4.0%). CONCLUSION: Right cardiac thrombosis, though difficult to assess clinically, is as common as left cardiac thrombosis and is associated with an increased risk of PE. The diagnosis should be considered in all cases of PE, especially in patients with atrial fibrillation or myocardial infarction and in the absence of confirmed deep vein thrombosis.
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| 6. |
- Seth, Henrik, 1979, et al.
(författare)
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Effects of gastric distension on the cardiovascular system in rainbow trout (Oncorhynchus mykiss).
- 2008
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Ingår i: American journal of physiology. Regulatory, integrative and comparative physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 294:5
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Tidskriftsartikel (refereegranskat)abstract
- When animals feed, blood flow to the gastrointestinal tract increases to ensure an adequate oxygen supply to the gastrointestinal tissue and an effective absorption of nutrients. In mammals, this increase depends on the chemical properties of the food, as well as, to some extent, on the mechanical distension of the stomach wall. By using an inflatable nitrile balloon positioned in the stomach, we investigated the cardiovascular responses to mechanical stretch of the stomach wall in rainbow trout (Oncorhynchus mykiss). Distension with a volume equivalent to a meal of 2% of the body mass increased dorsal aortic blood pressure by up to 29%, and central venous blood pressure increased transiently nearly fivefold. The increase in arterial pressure was mediated by an increased vascular resistance of both the systemic and the intestinal circulation. Cardiac output, heart rate, and stroke volume (SV) did not change, and only transient changes in gut blood flow were observed. The increase in arterial pressure was abolished by the alpha-adrenergic antagonist prazosin, indicating an active adrenergic vasoconstriction, whereas the venous pressor response could be the consequence of a passive increase in intraperitoneal pressure. Our results show that mechanical distension of the stomach causes an instantaneous increase in general vascular resistance, which may facilitate a redistribution of blood to the gastrointestinal tract when chemical stimuli from a meal induce vasodilation in the gut circulation. The normal postprandial increase in gut blood flow in teleosts is, therefore, most likely partly dependent on mechanical stimuli, as well as on chemical stimuli.
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| 7. |
- Stening, Kent, 1968-, et al.
(författare)
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Pain sensations to the cold pressor test in normally menstruating women : Comparison with men and relation to menstrual phase and serum sex steroid levels
- 2007
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Ingår i: American Journal of Physiology. Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 293:4
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Tidskriftsartikel (refereegranskat)abstract
- The role of gonadal hormones on pain sensations was investigated in normally menstruating women (n = 16) using the cold pressor test. Tolerance time, pain threshold, and pain intensity were examined once a week during a 4-wk period, and serum concentrations of 17β-estradiol and progesterone were determined at each test session, which were classified into the early follicular phase, late follicular phase, early luteal phase, and late luteal phase, as determined by the first day of menses and the actual hormone levels recorded. A group of men (n = 10) of the same age interval was examined for comparison. The data show that pain threshold was reduced during the late luteal phase compared with the late follicular phase, and hormone analyses showed significant positive correlation between the progesterone concentration and lowered pain threshold and increasing pain intensity. Hormone analysis also showed an interaction between S-estradiol and S-progesterone on pain intensity, demonstrating that the increased perceived pain intensity that was associated with high progesterone concentrations was significantly reduced with increasing levels of estradiol. While no statistically significant sex differences in pain measurements were found, women displayed much more pronounced, and statistically significant, session-to-session effects than men, with increased pain threshold and decreased pain intensity with each test session. Hence, these data suggest that the changes in the serum concentration of gonadal hormones that occur during the menstrual cycle influence pain sensations elicited by noxious tonic cold stimulation and show that adaptation to the cold pressor test may be sex dependent. © 2007 the American Physiological Society.
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| 8. |
- Strandberg, Joakim, 1978, et al.
(författare)
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Modulation of low-frequency-induced synaptic depression in the developing CA3-CA1 hippocampal synapses by NMDA and metabotropic glutamate receptor activation.
- 2009
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Ingår i: Journal of neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 101:5, s. 2252-62
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Tidskriftsartikel (refereegranskat)abstract
- Brief test-pulse stimulation (0.2-0.05 Hz) of naïve (previously nonstimulated) developing hippocampal CA3-CA1 synapses leads to a substantial synaptic depression, explained by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) silencing. Using field recordings in hippocampal slices from P8 to P12 rats, we examined this depression of naïve synapses using more prolonged test-pulse stimulation as well as low-frequency (1 Hz) stimulation (LFS). We found that 900 stimuli produced depression during stimulation to approximately 40% of the naïve level independent of whether test-pulse stimulation or LFS was used. This result was also observed during combined blockade of N-methyl-d-aspartate/metabotropic glutamate receptors (NMDAR/mGluRs) although the depression was smaller (to approximately 55% of naïve level). Using separate blockade of either NMDARs or mGluRs, we found that this impairment of the depression resulted from the NMDAR, and not from the mGluR, blockade. In fact, during NMDAR blockade alone, depression was smaller even than that observed during combined blockade. We also found that mGluR blockade alone facilitated the LFS-induced depression. In conclusion, test-pulse stimulation produced as much depression as LFS when applied to naïve synapses even when allowing for NMDAR and mGluR activation. Our results seem in line with the notion that NMDARs and mGluRs may exert a bidirectional control on AMPA receptor recruitment to synapses.
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| 9. |
- Sundqvist, Monika, 1976, et al.
(författare)
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Ontogeny of excitatory and inhibitory control of gastrointestinal motility in the African clawed frog, Xenopus laevis
- 2006
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Ingår i: American Journal of Physiology-Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 291:4
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Tidskriftsartikel (refereegranskat)abstract
- The transparent body wall of Xenopus laevis larvae during the first developmental stages allows in vivo studies of gastrointestinal tract activity. The purpose of this study was to chart the ontogeny of gut motility in Xenopus larvae and to identify the most important control systems during the first developmental stages. Coordinated descending contraction waves first occurred in the gut at Nieuwkoop and Faber stage 43 [0.8 +/- 0.1 contractions/min (cpm)] and increased to 4.9 +/- 0.1 cpm at stage 47. The cholinergic receptor agonist carbachol (5 - 10 mu M) increased contraction frequency already at stage 43, as did neurokinin A (NKA, 0.3 - 1 mu M). The muscarinic antagonist atropine (100 mu M) first affected contraction frequency at stage 45, which coincides with the onset of feeding. The tachykinin antagonist MEN-10,376 (6 mu M) blocked NKA-induced contractions but not spontaneous motility. Both sodium nitroprusside [nitric oxide (NO) donor, 1 - 10 mu M] and vasoactive intestinal peptide (VIP, 0.1 - 1 mu M) inhibited contractions from the earliest stage onward. Blocking NO synthesis using N-G-nitroL- arginine methyl ester (100 mu M) had no effect per se, but antagonized VIP evoked inhibition at stage 47. We conclude that gastrointestinal motility is well developed in the Xenopus laevis larvae before the onset of feeding. Functional muscarinic and tachykinin receptors are present already at the onset of motility, whereas a cholinergic tone develops around the onset of feeding. No endogenous tachykinin tone was found. Functional VIP receptors mediate inhibition at the onset of motility. NO seems to mediate the VIP effect at later stages.
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| 10. |
- Baklanov, D. V., et al.
(författare)
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Comparison of transendocardial and retrograde coronary venous intramyocardial catheter delivery systems in healthy and infarcted pigs
- 2006
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Ingår i: Catheterization and cardiovascular interventions. - : Wiley-Blackwell. - 1522-1946 .- 1522-726X. ; 68:3, s. 416-423
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Tidskriftsartikel (refereegranskat)abstract
- We compared two routes for myocardial delivery of therapeutics, transendocardial (TE) delivery with an intramyocardial injection catheter, and retrograde coronary venous (RCV) delivery with a balloon occlusion catheter in the interventricular vein. Methods: TE and RCV injection of 15 mu m, neutron-activatable microspheres was compared in healthy pigs (Group I, n = 3), pigs with a 1-week-old myocardial infarction (MI; group II, n = 5), and pigs with a 2-weeks-old MI (group III, n = 4). The MI was induced by a 1-hr balloon occlusion in the LAD. Both methods were compared in the same animal using different microspheres. The RCV catheter allowed for continuous measurement of distal pressure and 2.5 x 10(6) microspheres were injected in 10 ml at 300 mmHg above balloon occlusion pressure. The TE injections were targeted to the infarct zone and 2.5 x 10(6) microspheres were distributed over 10 injections of 200 mu l. Results: The retention of microspheres decreased with increase in MI age, but was comparable between devices within the groups. RCV delivery resulted in (14.3 +/- 0.9)% microsphere retention in Group I, (10.3 +/- 0.2)% in Group II, and (6.4 +/- 0.1)% in group III (P less than 0.05 versus group I). Microsphere retention after TE was (15.1 +/- 0.7)% in group I, (18.9 +/- 0.6)% in group II, (4.1 +/- 0.1)% in Group III (P less than 0.05 versus groups I and II). The RCV catheter delivered primarily to midventricular, antero-septal segments, whereas TE targeted apical areas predominantly. Conclusions: Delivery efficacy was comparable between devices in each group however RCV targeted midventricular areas whereas TE targeted apical areas.
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