| 6351. |
- Björefeldt, Andreas, 1982, et al.
(författare)
-
Efficient opto- and chemogenetic control in a single molecule driven by FRET-modified bioluminescence
- 2024
-
Ingår i: NEUROPHOTONICS. - 2329-423X .- 2329-4248. ; 11:2
-
Tidskriftsartikel (refereegranskat)abstract
- Significance Bioluminescent optogenetics (BL-OG) offers a unique and powerful approach to manipulate neural activity both opto- and chemogenetically using a single actuator molecule (a LuMinOpsin, LMO). Aim To further enhance the utility of BL-OG by improving the efficacy of chemogenetic (bioluminescence-driven) LMO activation. Approach We developed novel luciferases optimized for F & ouml;rster resonance energy transfer when fused to the fluorescent protein mNeonGreen, generating bright bioluminescent (BL) emitters spectrally tuned to Volvox Channelrhodopsin 1 (VChR1). Results A new LMO generated from this approach (LMO7) showed significantly stronger BL-driven opsin activation compared to previous and other new variants. We extensively benchmarked LMO7 against LMO3 (current standard) and found significantly stronger neuronal activity modulation ex vivo and in vivo, and efficient modulation of behavior. Conclusions We report a robust new option for achieving multiple modes of control in a single actuator and a promising engineering strategy for continued improvement of BL-OG.
|
|
| 6352. |
- Björefeldt, Andreas, 1982, et al.
(författare)
-
Human cerebrospinal fluid increases the excitability of pyramidal neurons in the in vitro brain slice.
- 2015
-
Ingår i: The Journal of physiology. - : Wiley. - 1469-7793 .- 0022-3751. ; 593:1, s. 231-43
-
Tidskriftsartikel (refereegranskat)abstract
- The cerebrospinal fluid contains numerous neuromodulators at ambient levels but whether, and how, they affect the activity of central neurons is unknown. This study provides experimental evidence that human cerebrospinal fluid (hCSF) increases the excitability of hippocampal and neocortical pyramidal neurons. Hippocampal CA1 pyramidal neurons in hCSF displayed lowered firing thresholds, depolarized resting membrane potentials and reduced input resistance, mimicking properties of pyramidal neurons recorded in vivo. The excitability-increasing effect of hCSF on CA1 pyramidal neurons was entirely occluded by intracellular application of GTPγS, suggesting that neuromodulatory effects were mediated by G-protein coupled receptors. These results indicate that the CSF promotes spontaneous excitatory neuronal activity, and may help to explain observed differences in the activity of pyramidal neurons recorded in vivo and in vitro.
|
|
| 6353. |
- Björefeldt, Andreas, 1982, et al.
(författare)
-
Neuromodulation of fast-spiking and non-fast-spiking hippocampal CA1 interneurons by human cerebrospinal fluid.
- 2016
-
Ingår i: The Journal of physiology. - 1469-7793. ; 594:4, s. 937-52
-
Tidskriftsartikel (refereegranskat)abstract
- GABAergic interneurons intricately regulate the activity of hippocampal and neocortical networks. Their function in vivo is likely to be tuned by neuromodulatory substances in brain extracellular fluid. However, in vitro investigations of GABAergic interneuron function do not account for such effects, as neurons are kept in artificial extracellular fluid. To examine the neuromodulatory influence of brain extracellular fluid on GABAergic activity, we recorded from fast-spiking and non-fast-spiking CA1 interneurons, as well as from pyramidal cells, in the presence of human cerebrospinal fluid (hCSF), using a matched artificial cerebrospinal (aCSF) fluid as control. We found that hCSF increased the frequency of spontaneous firing more than twofold in the two groups of interneurons, and more than fourfold in CA1 pyramidal cells. hCSF did not affect the resting membrane potential of CA1 interneurons but caused depolarization in pyramidal cells. The increased excitability of interneurons and pyramidal cells was accompanied by reductions in afterhyperpolarization amplitudes and a left-shift in the frequency-current relationships. Our results suggest that ambient concentrations of neuromodulators in the brain extracellular fluid powerfully influence the excitability of neuronal networks. This article is protected by copyright. All rights reserved.
|
|
| 6354. |
- Björefeldt, Andreas, 1982, et al.
(författare)
-
Neuromodulation via the Cerebrospinal Fluid: Insights from Recent in Vitro Studies.
- 2018
-
Ingår i: Frontiers in neural circuits. - : Frontiers Media SA. - 1662-5110. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- The cerebrospinal fluid (CSF) occupies the brain's ventricles and subarachnoid space and, together with the interstitial fluid (ISF), forms a continuous fluidic network that bathes all cells of the central nervous system (CNS). As such, the CSF is well positioned to actively distribute neuromodulators to neural circuitsin vivovia volume transmission. Recentin vitroexperimental work in brain slices and neuronal cultures has shown that human CSF indeed contains neuromodulators that strongly influence neuronal activity. Here we briefly summarize these new findings and discuss their potential relevance to neural circuits in health and disease.
|
|
| 6355. |
- Björk, Karl, et al.
(författare)
-
Ethanol-induced activation of AKT and DARPP-32 in the mouse striatum mediated by opioid receptors
- 2010
-
Ingår i: Addiction Biology. - : Wiley-Blackwell. - 1355-6215 .- 1369-1600. ; 15:3, s. 299-303
-
Tidskriftsartikel (refereegranskat)abstract
- The reinforcing properties of ethanol are in part attributed to interactions between opioid and dopaminergic signaling pathways, but intracellular mediators of such interactions are poorly understood. Here we report that an acute ethanol challenge induces a robust phosphorylation of two key signal transduction kinases, AKT and DARPP-32, in the striatum of mice. Ethanol-induced AKT phosphorylation was blocked by the opioid receptor antagonist naltrexone but unaffected by blockade of dopamine D2 receptors via sulpiride. In contrast, DARPP-32 phosphorylation was abolished by both antagonists. These data suggest that ethanol acts via two distinct but potentially synergistic striatal signaling cascades. One of these is D2-dependent, while the other is not. These findings illustrate that pharmacology of ethanol reward is likely more complex than that for other addictive drugs.
|
|
| 6356. |
- Björk, Karl, et al.
(författare)
-
β-Arrestin 2 knockout mice exhibit sensitized dopamine release and increased reward in response to a low dose of alcohol
- 2013
-
Ingår i: Psychopharmacology. - : Springer. - 0033-3158 .- 1432-2072. ; 230:3, s. 439-449
-
Tidskriftsartikel (refereegranskat)abstract
- RationaleThe rewarding effects of alcohol have been attributed to interactions between opioid and dopaminergic system within the mesolimbic reward pathway. We have previously shown that ablation of β-arrestin 2 (Arrb2), a crucial regulator of μ-opioid receptor function, attenuates alcohol-induced hyperlocomotion and c-fos activation in the nucleus accumbens.ObjectivesHere, we further investigated the role of Arrb2 in modulating alcohol-induced dopamine (DA) release and conditioned place preference (CPP). We also assessed the functional importance of Arrb2 for μ-opioid receptor surface expression and signaling following an acute alcohol challenge.MethodsAlcohol-evoked (0.375, 0.75, and 1.5 g/kg intraperitoneally) DA release was measured by in vivo microdialysis in the shell of nucleus accumbens. Reward was assessed by the CPP paradigm. Receptor function was assessed by μ-receptor binding and [35S]GTP-γ-S autoradiography.ResultsIn Arrb2 knockout mice accumbal DA levels reach maximum response at a lower dose compared to wild-type (wt) animals. In line with these results, Arrb2 knockout mice display increased CPP for alcohol as compared to wt mice. Finally, Arrb2 mutant mice display increased μ-opioid receptor signaling in the ventral and dorsal striatum and amygdala in response to a low dose of alcohol, indicating impaired desensitization mechanisms in these mice.ConclusionsOur results show that Arrb2 modulates the response to low doses of alcohol on various levels including μ-opioid receptor signaling, DA release, and reward. They also reveal a clear dissociation between the effects of Arrb2 on psychomotor and reward behaviors.
|
|
| 6357. |
- Björkdahl, Ann, 1959, et al.
(författare)
-
EXPLORING THE IMPACT OF COGNITIVE DYSFUNCTION, FATIGUE, AND SHORTNESS OF BREATH ON ACTIVITIES OF DAILY LIFE AFTER COVID-19 INFECTION, UNTIL 1-YEAR FOLLOW-UP
- 2024
-
Ingår i: JOURNAL OF REHABILITATION MEDICINE. - 1650-1977 .- 1651-2081. ; 56
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Despite expanding knowledge on COVID-19, the long-term effects on daily -life activities remain unclear. The prevalence and changes in fatigue, cognitive dysfunction, and activity limitations in the first year after COVID-19 infection in hospitalized and non -hospitalized patients were explored. Subjects: A total of 122 patients were recruited from hospital care and 90 from primary care. Method: Baseline data comprised the Montreal Cognitive Assessment and Trail Making Test. Participants were followed up at 3 and 12 months using these tests and a semi -structured interview to identify symptoms and how they affected participation in daily -life activities. Both within- and betweengroup analyses were performed to explore changes over time and compare groups. Result: High levels of fatigue and cognitive dysfunction were found in both groups, which persisted for 12 months. A significant impact on daily -life activities was also observed, with marginal change at the 12 -month follow-up. The hospital care group performed worse than the primary care group in the cognitive tests, although the primary care group perceived a higher level of fatigue and cognitive dysfunction. Activity limitations were higher in the primary care group than in the hospital care group. Conclusion: These findings highlight the need for long-term follow-up and further investigation of the impact of persistent deficits on rehabilitation.
|
|
| 6358. |
- Björkdahl, Ann, 1959-, et al.
(författare)
-
Neuropsykologisk rehabilitering
- 2014. - 2
-
Ingår i: Klinisk neuropsykologi. - Lund : Studentlitteratur AB. - 9789144040479
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
|
|
| 6359. |
|
|
| 6360. |
- Björklund, Anders, et al.
(författare)
-
A Combined α-Synuclein/Fibril (SynFib) Model of Parkinson-Like Synucleinopathy Targeting the Nigrostriatal Dopamine System
- 2022
-
Ingår i: Journal of Parkinson's Disease. - 1877-718X. ; 12:8, s. 2307-2320
-
Forskningsöversikt (refereegranskat)abstract
- Injections of pre-formed α-synuclein fibrils (PFFs) or overexpression of α-synuclein using AAV vectors are commonly used as models of Parkinson-like synucleinopathy in rats and mice. In the modified method reviewed here, the "SynFib" model, the PFFs and the AAV vector are administered together unilaterally into the substantia nigra. This approach combines the key features of these two models, i.e., the generation of toxic α-synuclein aggregates and Lewy body-like inclusions, in combination with the increased vulnerability caused by increased cellular levels of α-synuclein. The combined AAV/PFF delivery offers several advantages over the standard PFF model due to the enhanced and accelerated α-synuclein pathology and microglial response induced by the PFF seeds in the presence of an elevated α-synuclein level. Injection of the AAV/PFF mixture into the substantia nigra makes it possible to target a larger proportion of the nigral dopamine neurons and obtain a level of dopamine cell loss (>60%) needed to induce significant impairments in drug-induced and spontaneous motor tests. The SynFib model shares attractive features of the standard 6-OHDA lesion model: a single unilateral stereotaxic intervention; pathology and cell loss developing over a short time span; and the possibility to monitor the degenerative changes using tests of motor behavior.
|
|
