| 1. |
- Bakalkin, Georgy, et al.
(författare)
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Coordinated expression of the renin-angiotensin genes in the lumbar spinal cord : Lateralization and effects of unilateral brain injury
- 2021
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Ingår i: European Journal of Neuroscience. - : John Wiley & Sons. - 0953-816X .- 1460-9568. ; 54:4, s. 5560-5573
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Tidskriftsartikel (refereegranskat)abstract
- In spite of its apparent symmetry, the spinal cord is asymmetric in its reflexes and gene expression patterns including leftward expression bias of the opioid and glutamate genes. To examine whether this is a general phenomenon for neurotransmitter and neurohormonal genes, we here characterized expression and co-expression (transcriptionally coordinated) patterns of genes of the renin-angiotensin system (RAS) that is involved in neuroprotection and pathological neuroplasticity in the left and right lumbar spinal cord. We also tested whether the RAS expression patterns were affected by unilateral brain injury (UBI) that rewired lumbar spinal neurocircuits. The left and right halves of the lumbar spinal cord were analysed in intact rats, and rats with left- or right-sided unilateral cortical injury, and left- or right-sided sham surgery. The findings were (i) lateralized expression of the RAS genes Ace, Agtr2 and Ren with higher levels on the left side; (ii) the asymmetry in coordination of the RAS gene expression that was stronger on the right side; (iii) the decay in coordination of co-expression of the RAS and neuroplasticity-related genes induced by the right-side but not left-side sham surgery and UBI; and (iv) the UBI-induced shift to negative regulatory interactions between RAS and neuroplasticity-related genes on the contralesional spinal side. Thus, the RAS genes may be a part of lateralized gene co-expression networks and have a role in a side-specific regulation of spinal neurocircuits.
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| 2. |
- Carvalho, Liliana S., et al.
(författare)
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Unilateral brain injury to pregnant rats induces asymmetric neurological deficits in the offspring
- 2021
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Ingår i: European Journal of Neuroscience. - : John Wiley & Sons. - 0953-816X .- 1460-9568. ; 53:11, s. 3621-3633
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Tidskriftsartikel (refereegranskat)abstract
- Effects of environmental factors may be transmitted to the following generation, and cause neuropsychiatric disorders including depression, anxiety, and posttraumatic stress disorder in the offspring. Enhanced synaptic plasticity induced by environmental enrichment may be also transmitted. We here test the hypothesis that the effects of brain injury in pregnant animals may produce neurological deficits in the offspring. Unilateral brain injury (UBI) by ablation of the hindlimb sensorimotor cortex in pregnant rats resulted in the development of hindlimb postural asymmetry (HL-PA), and impairment of balance and coordination in beam walking test in the offspring. The offspring of rats with the left UBI exhibited HL-PA before and after spinal cord transection with the contralesional (i.e., right) hindlimb flexion. The right UBI caused the offspring to develop HL-PA that however was cryptic and not-lateralized; it was evident only after spinalization, and was characterized by similar occurrence of the ipsi- and contralesional hindlimb flexion. The HL-PA persisted after spinalization suggesting that the asymmetry was encoded in lumbar spinal neurocircuits that control hindlimb muscles. Balance and coordination were affected by the right UBI but not the left UBI. Thus, the effects of a unilateral brain lesion in pregnant animals may be intergenerationally transmitted, and this process may depend on the side of brain injury. The results suggest the existence of left-right side-specific mechanisms that mediate transmission of the lateralized effects of brain trauma from mother to fetus.
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| 3. |
- Fischi-Gomez, E., et al.
(författare)
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Ultrahigh field in vivo characterization of microstructural abnormalities in the orbitofrontal cortex and amygdala in autism
- 2021
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Ingår i: European Journal of Neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 54:6, s. 6229-6236
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Tidskriftsartikel (refereegranskat)abstract
- There are currently no biomarkers for autism spectrum disorder (ASD). This neurodevelopmental condition has previously been associated with histopathological findings, including increased neuronal packing density in the amygdala, abnormal laminar cytoarchitecture and increased average neuronal density in the prefrontal cortex. The present study examined whether new brain imaging technologies could reveal in vivo, in adults with ASD, the manifestation of previously described histopathological changes. Using quantitative mapping at ultrahigh field (7 Tesla), we show that we can observe microstructural alterations in the right lateral orbitofrontal cortex and the bilateral amygdala in adult individuals with ASD in vivo. These imaging alterations point to an abnormal laminar cytoarchitecture and to an increased neuronal density, similar to what has been previously described in post-mortem data in ASD. Our data demonstrate that it is possible to visualize, in vivo and at the individual level, alterations of cortical and subcortical microstructure in ASD. Future studies will be needed to extend these findings to a larger group of individuals and evaluate their association with symptomatology as well as their specificity among the different neurodevelopmental disorders.
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| 4. |
- Frost Nylén, J, et al.
(författare)
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Reciprocal interaction between striatal cholinergic and low-threshold spiking interneurons - A computational study
- 2020
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Ingår i: European Journal of Neuroscience. - : Blackwell Publishing Ltd. - 0953-816X .- 1460-9568.
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Tidskriftsartikel (refereegranskat)abstract
- The striatum is the main input stage of the basal ganglia receiving extrinsic input from cortex and thalamus. The striatal projection neurons (SPN) constitute 95% of the neurons in the striatum in mice while the remaining 5% are cholinergic and GABAergic interneurons. The cholinergic (ChIN) and low-threshold spiking interneurons (LTS) are spontaneously active and form a striatal subnetwork involved in salience detection and goal-directed learning. Activation of ChINs has been shown to inhibit LTS via muscarinic receptor type 4 (M4R) and LTS in turn can modulate ChINs via nitric oxide (NO) causing a prolonged depolarization. Thalamic input prefentially excites ChINs, whereas input from motor cortex favours LTS, but can also excite ChINs. This varying extrinsic input with intrinsic reciprocal, yet opposing, effects raises the possibility of a slow input-dependent modulatory subnetwork. Here, we simulate this subnetwork using multicompartmental neuron models that incorporate data regarding known ion channels and detailed morphological reconstructions. The modelled connections replicate the experimental data on muscarinic (M4R) and nitric oxide modulation onto LTS and ChIN, respectively, and capture their physiological interaction. Finally, we show that the cortical and thalamic inputs triggering the opposing modulation within the network induce periods of increased and decreased spiking activity in ChINs and LTS. This could provide different temporal windows for selective modulation by acetylcholine and nitric oxide, and the possibility of interaction with the wider striatal microcircuit.
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| 5. |
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| 6. |
- Lguensat, Asmae, 1993-, et al.
(författare)
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Repeated ethanol exposure following avoidance conditioning impairs avoidance extinction and modifies conditioning‐associated prefrontal dendritic changes in a mouse model of post‐traumatic stress disorder
- 2021
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Ingår i: European Journal of Neuroscience. - : Wiley-Blackwell Publishing Inc.. - 0953-816X .- 1460-9568. ; 54:10, s. 7710-7732
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Tidskriftsartikel (refereegranskat)abstract
- Treatment of post-traumatic stress disorder is complicated by the presence of alcohol use disorder comorbidity. Little is known about the underlying brain mechanisms. We have recently shown, in mice, that the post-traumatic stress disorder-like phenotype is characterised by the increase and decrease in total dendritic number and length in the prelimbic and infralimbic areas of the medial prefrontal cortex, respectively. Here, we examined whether repeated ethanol exposure would exacerbate these changes and whether this would be associated with difficulty to extinguish passive avoidance behaviour, as an indicator of treatment resistance. We also analysed whether other known trauma-associated changes, like increased or decreased corticosterone and decreased brain-derived neurotrophic factor levels, would also be exacerbated. Male mice underwent trauma exposure (1.5-mA footshock), followed, 8 days later, by a conditioned place preference training with ethanol. Tests for fear sensitization, passive avoidance, anxiety-like behaviour, extinction acquisition and relapse susceptibility were used to assess behaviour changes. Plasma corticosterone and brain-derived neurotrophic factor levels and prefrontal dendritic changes were subsequently measured. Trauma-susceptible mice exposed to ethanol acquired a strong place preference and behaved differently from those not exposed to ethanol, with delayed avoidance extinction and higher avoidance relapse vulnerability. Ethanol potentiated trauma-associated dendritic changes in the prelimbic area and suppressed trauma-associated dendritic changes in the infralimbic area. However, ethanol had no effect on trauma-induced increased corticosterone and decreased brain-derived neurotrophic factor levels. These data suggest that the modification of prefrontal trauma-related changes, due to alcohol use, can characterise, and probably support, treatment-resistant post-traumatic stress disorder.
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| 7. |
- Lindroos, R., et al.
(författare)
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Predicting complex spikes in striatal projection neurons of the direct pathway following neuromodulation by acetylcholine and dopamine
- 2020
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Ingår i: European Journal of Neuroscience. - : Blackwell Publishing Ltd. - 0953-816X .- 1460-9568.
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Tidskriftsartikel (refereegranskat)abstract
- The input structure of the basal ganglia, striatum, receives dense neuromodulatory input in the form of dopamine and acetylcholine. The two systems are tightly connected, for example, synchronized activity of cholinergic interneurons, leading to increased acetylcholine release, has been shown to directly trigger dopamine release from dopaminergic terminals in striatum. Both signals are further needed for induction of locomotion. High dopamine concentration leads to increased excitability of the direct pathway striatal projection neurons. High cholinergic tone inhibits various potassium channels further increasing the excitability of striatal projection neurons. Here, we investigate the combined effect of concurrent high acetylcholine and dopamine using biophysically detailed models based on rodent data. The aim of the study is to investigate how neuromodulation affects dendritic integration. The result shows that neuromodulation paired with synaptic activation of dendrites can give rise to complex spiking patterns, resembling spike shapes seen in the hippocampus. In the hippocampus, these complex spikes are associated with behavioral time scale plasticity and place cell tuning. We further investigate the mechanisms behind the complex spikes and find that there are two components, one axo-somatic and one dendritic in origin.
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| 8. |
- Ma, Rong, et al.
(författare)
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Homosynaptic frequency-dependent depression by release site inactivation at neonatal hippocampal synapses in the stratum lacunosum-moleculare
- 2021
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Ingår i: European Journal of Neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 54:3, s. 4838-4862
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Tidskriftsartikel (refereegranskat)abstract
- When activated at low frequencies (0.1-1 Hz), second postnatal week synapses onto the most distal part of the apical dendritic tree (stratum lacunosum-moleculare) of rat hippocampal CA1 pyramidal cells display a frequency-dependent synaptic depression not observed for the more proximal (stratum radiatum) synapses. Depression in this frequency range is thought of as a possible contributor to behavioural habituation. In fact, in contrast to the proximal synapses, the distal synapses provide more direct sensory information from the entorhinal cortex as well as from thalamic nuclei. The use of antagonists showed that the activation of GABA(A), GABA(B), NMDA, mGlu, kainate, adenosine, or endocannabinoid receptors was not directly involved in the depression, indicating it to be intrinsic to the synapses themselves. While the depression affected paired-pulse plasticity in a manner indicating a decrease in vesicle release probability, the depression could not be explained by a stimulus-dependent decrease in calcium influx. Despite affecting the synaptic response evoked by brief high-frequency stimulation (10 impulses, 20 Hz) in a manner indicating vesicle depletion, the depression was unaffected by large variations in release probability. The depression was found not only to affect the synaptic transmission at low frequencies (0.1-1 Hz) but also to contribute to the depression evolving during brief high-frequency stimulation (10 impulses, 20 Hz). We propose that a release-independent process directly inactivating release sites with a fast onset (ms) and long duration (up to 20 s) underlies this synaptic depression.
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| 9. |
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| 10. |
- Mohagheghi Nejad, Mohammadreza, et al.
(författare)
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Basal ganglia and cortical control of thalamic rebound spikes
- 2021
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Ingår i: European Journal of Neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 54:1, s. 4295-4313
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Tidskriftsartikel (refereegranskat)abstract
- Movement-related decreases in firing rate have been observed in basal ganglia output neurons. They may transmit motor signals to the thalamus, but the effect of these firing rate decreases on downstream neurons in the motor thalamus is not known. One possibility is that they lead to thalamic post-inhibitory rebound spikes. However, it has also been argued that the physiological conditions permitting rebound spiking are pathological, and primarily present in Parkinson's disease. As in Parkinson's disease neural activity becomes pathologically correlated, we investigated the impact of correlations in basal ganglia output on the transmission of motor signals using a Hodgkin-Huxley model of thalamocortical neurons. We found that such correlations disrupt the transmission of motor signals via rebound spikes by decreasing the signal-to-noise ratio and increasing the trial-to-trial variability. We further examined the role of sensory responses in basal ganglia output neurons and the effect of cortical excitation of motor thalamus in modulating rebound spiking. Interestingly, both could either promote or suppress the generation of rebound spikes depending on their timing relative to the motor signal. Finally, we determined parameter regimes, such as levels of excitation, under which rebound spiking is feasible in the model, and confirmed that the conditions for rebound spiking are primarily given in pathological regimes. However, we also identified specific conditions in the model that would allow rebound spiking to occur in healthy animals in a small subset of thalamic neurons. Overall, our model provides novel insights into differences between normal and pathological transmission of motor signals.
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