| 1. |
- Adey, Brett N., et al.
(författare)
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Large-scale analyses of CAV1 and CAV2 suggest their expression is higher in post-mortem ALS brain tissue and affects survival
- 2023
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Ingår i: Frontiers in Cellular Neuroscience. - : Frontiers Media S.A.. - 1662-5102. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Caveolin-1 and Caveolin-2 (CAV1 and CAV2) are proteins associated with intercellular neurotrophic signalling. There is converging evidence that CAV1 and CAV2 (CAV1/2) genes have a role in amyotrophic lateral sclerosis (ALS). Disease-associated variants have been identified within CAV1/2 enhancers, which reduce gene expression and lead to disruption of membrane lipid rafts.Methods: Using large ALS whole-genome sequencing and post-mortem RNA sequencing datasets (5,987 and 365 tissue samples, respectively), and iPSC-derived motor neurons from 55 individuals, we investigated the role of CAV1/2 expression and enhancer variants in the ALS phenotype.Results: We report a differential expression analysis between ALS cases and controls for CAV1 and CAV2 genes across various post-mortem brain tissues and three independent datasets. CAV1 and CAV2 expression was consistently higher in ALS patients compared to controls, with significant results across the primary motor cortex, lateral motor cortex, and cerebellum. We also identify increased survival among carriers of CAV1/2 enhancer mutations compared to non-carriers within Project MinE and slower progression as measured by the ALSFRS. Carriers showed a median increase in survival of 345 days.Discussion: These results add to an increasing body of evidence linking CAV1 and CAV2 genes to ALS. We propose that carriers of CAV1/2 enhancer mutations may be conceptualised as an ALS subtype who present a less severe ALS phenotype with a longer survival duration and slower progression. Upregulation of CAV1/2 genes in ALS cases may indicate a causal pathway or a compensatory mechanism. Given prior research supporting the beneficial role of CAV1/2 expression in ALS patients, we consider a compensatory mechanism to better fit the available evidence, although further investigation into the biological pathways associated with CAV1/2 is needed to support this conclusion.
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| 2. |
- Andersson, Martin N, et al.
(författare)
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A sex pheromone receptor in the Hessian fly Mayetiola destructor (Diptera, Cecidomyiidae)
- 2016
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Ingår i: Frontiers in Cellular Neuroscience. - : Frontiers Media SA. - 1662-5102. ; 10:SEP2016
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Tidskriftsartikel (refereegranskat)abstract
- The Hessian fly, Mayetiola destructor Say (Diptera, Cecidomyiidae), is a pest of wheat and belongs to a group of gall-inducing herbivores. This species has a unique life history and several ecological features that differentiate it from other Diptera such as Drosophila melanogaster and blood-feeding mosquitoes. These features include a short, non-feeding adult life stage (1–2 days) and the use of a long-range sex pheromone produced and released by adult females. Sex pheromones are detected by members of the odorant receptor (OR) family within the Lepidoptera, but no receptors for similar long-range sex pheromones have been characterized from the Diptera. Previously, 122 OR genes have been annotated from the Hessian fly genome, with many of them showing sex-biased expression in the antennae. Here we have expressed, in HEK293 cells, five MdesORs that display male-biased expression in antennae, and we have identified MdesOR115 as a Hessian fly sex pheromone receptor. MdesOR115 responds primarily to the sex pheromone component (2S,8E,10E)-8,10-tridecadien-2-yl acetate, and secondarily to the corresponding Z,E-isomer. Certain sensory neuron membrane proteins (i.e., SNMP1) are important for responses of pheromone receptors in flies and moths. The Hessian fly genome is unusual in that it encodes six SNMP1 paralogs, of which five are expressed in antennae. We co-expressed each of the five antennal SNMP1 paralogs together with each of the five candidate sex pheromone receptors from the Hessian fly and found that they do not influence the response of MdesOR115, nor do they confer responsiveness in any of the non-responsive ORs to any of the sex pheromone components identified to date in the Hessian fly. Using Western blots, we detected protein expression of MdesOrco, all MdesSNMPs, and all MdesORs except for MdesOR113, potentially explaining the lack of response from this OR. In conclusion, we report the first functional characterization of an OR from the Cecidomyiidae, extending the role of ORs as long-range sex pheromone detectors from the Lepidoptera into the Diptera.
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| 3. |
- Anzabi, M., et al.
(författare)
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Hippocampal Atrophy Following Subarachnoid Hemorrhage Correlates with Disruption of Astrocyte Morphology and Capillary Coverage by AQP4
- 2018
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Ingår i: Frontiers in Cellular Neuroscience. - : Frontiers Media SA. - 1662-5102. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Despite successful management of ruptured intracranial aneurysm following subarachnoid hemorrhage (SAH), delayed cerebral ischemia (DCI) remains the main cause of high mortality and morbidity in patients who survive the initial bleeding. Astrocytes play a key role in neurovascular coupling. Therefore, changes in the neurovascular unit including astrocytes following SAH may contribute to the development of DCI and long-term complications. In this study, we characterized morphological changes in hippocampal astrocytes following experimental SAH, with special emphasis on glia-vascular cross-talk and hippocampal volume changes. Four days after induction of SAH or sham-operation in mice, their hippocampal volumes were determined by magnetic resonance imaging (MRI) and histological/stereological methods. Glial fibrillary acid protein (GFAP) immunostained hippocampal sections were examined by stereological techniques to detect differences in astrocyte morphology, and global spatial sampling method was used to quantify the length density of Aquaporin-4 (AQP4) positive capillaries. Our results indicated that hippocampal volume, as measured both by MRI and by histological approaches, was significantly lower in SAH animals than in the sham-operated group. Accordingly, in this animal model of SAH, hippocampal atrophy existed already at the time of DCI onset in humans. SAH induced retraction of GFAP positive astrocyte processes, accompanied by a significant reduction in the length density of AQP4 positive capillaries as well as narrowing of hippocampal capillaries. Meanwhile, astrocyte volume was higher in SAH mice compared with the sham-operated group. Morphological changes in hippocampal astrocytes seemingly disrupt glia-vascular interactions early after SAH and may contribute to hippocampal atrophy. We speculate that astrocytes and astrocyte-capillary interactions may provide targets for the development of therapies to improve the prognosis of SAH.
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| 4. |
- Bachiller, Sara, et al.
(författare)
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Microglia in neurological diseases : A road map to brain-disease dependent-inflammatory response
- 2018
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Ingår i: Frontiers in Cellular Neuroscience. - : Frontiers Media SA. - 1662-5102. ; 12
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Forskningsöversikt (refereegranskat)abstract
- Microglia represent a specialized population of macrophages-like cells in the central nervous system (CNS) considered immune sentinels that are capable of orchestrating a potent inflammatory response. Microglia are also involved in synaptic organization, trophic neuronal support during development, phagocytosis of apoptotic cells in the developing brain, myelin turnover, control of neuronal excitability, phagocytic debris removal as well as brain protection and repair. Microglial response is pathology dependent and affects to immune, metabolic. In this review, we will shed light on microglial activation depending on the disease context and the influence of factors such as aging, environment or cell-to-cell interaction.
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| 5. |
- Batra, Srishti, et al.
(författare)
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A functional agonist of insect olfactory receptors : Behavior, physiology and structure
- 2019
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Ingår i: Frontiers in Cellular Neuroscience. - : Frontiers Media SA. - 1662-5102. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Chemical signaling is ubiquitous and employs a variety of receptor types to detect the cacophony of molecules relevant for each living organism. Insects, our most diverse taxon, have evolved unique olfactory receptors with as little as 10% sequence identity between receptor types. We have identified a promiscuous volatile, 2-methyltetrahydro-3-furanone (coffee furanone), that elicits chemosensory and behavioral activity across multiple insect orders and receptors. In vivo and in vitro physiology showed that coffee furanone was detected by roughly 80% of the recorded neurons expressing the insect-specific olfactory receptor complex in the antenna of Drosophila melanogaster, at concentrations similar to other known, and less promiscuous, ligands. Neurons expressing specialized receptors, other chemoreceptor types, or mutants lacking the complex entirely did not respond to this compound. This indicates that coffee furanone is a promiscuous ligand for the insect olfactory receptor complex itself and did not induce non-specific cellular responses. In addition, we present homology modeling and docking studies with selected olfactory receptors that suggest conserved interaction regions for both coffee furanone and known ligands. Apart from its physiological activity, this known food additive elicits a behavioral response for several insects, including mosquitoes, flies, and cockroaches. A broad-scale behaviorally active molecule non-toxic to humans thus has significant implications for health and agriculture. Coffee furanone serves as a unique tool to unlock molecular, physiological, and behavioral relationships across this diverse receptor family and animal taxa.
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| 6. |
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| 7. |
- Bengtsson, Fredrik, et al.
(författare)
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Climbing Fiber Coupling between Adjacent Purkinje Cell Dendrites in Vivo.
- 2009
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Ingår i: Frontiers in Cellular Neuroscience. - : Frontiers Media SA. - 1662-5102. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Climbing fiber discharges within the rat cerebellar cortex have been shown to display synchrony, especially for climbing fibers terminating in the same parasagittal bands. In addition, Purkinje cells which have the smallest rostrocaudal separation also seem to have the highest degree of synchrony. But this has so far only been investigated for distances down to 250 mum. In the present study, we wanted to investigate whether Purkinje cells that are located immediately next to each other display a particularly pronounced synchrony in their climbing fiber discharges. To this end, we used a previously undescribed type of electrophysiological recording, a single electrode, loose patch, dual dendritic recording, from pairs of adjacent Purkinje cells in the decerebrated, non-anesthetized cat. From each recorded dendrite, this technique provided well isolated, unitary calcium spikes, which we found to have a spontaneous activity that was essentially identical with the pattern of spontaneous climbing fiber discharges. By calculating the coupling in firing between the adjacent dendrites, we found that most climbing fiber responses occurred independently of each other and that the probability of coupled discharges was less than 8%. These values are comparable to those obtained in previous studies for Purkinje cells located within the same parasagittal band and show that climbing fiber coupling within a microzone exists also in non-rodent mammalian species. However, since the degree of synchrony of climbing fiber discharge was not particularly pronounced in adjacent Purkinje cells, it seems unlikely that climbing fiber synchrony has pronounced systematic regional variations within the same microzone.
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| 8. |
- Bhandage, Amol K., 1988-, et al.
(författare)
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GABA-A and NMDA receptor subunit mRNA expression is altered in the caudate but not the putamen of the postmortem brains of alcoholics
- 2014
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Ingår i: Frontiers in Cellular Neuroscience. - : Frontiers. - 1662-5102. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Chronic consumption of alcohol by humans has been shown to lead to impairment of executive and cognitive functions. Here, we have studied the mRNA expression of ion channel receptors for glutamate and GABA in the dorsal striatum of post-mortem brains from alcoholics (n = 29) and normal controls (n = 29), with the focus on the caudate nucleus that is associated with the frontal cortex executive functions and automatic thinking and on the putamen area that is linked to motor cortices and automatic movements. The results obtained by qPCR assay revealed significant changes in the expression of specific excitatory ionotropic glutamate and inhibitory GABA-A receptor subunit genes in the caudate but not the putamen. Thus, in the caudate we found reduced levels of mRNAs encoding the GluN2A glutamate receptor and the δ, ε, and ρ2 GABA-A receptor subunits, and increased levels of the mRNAs encoding GluD1, GluD2, and GABA-A γ1 subunits in the alcoholics as compared to controls. Interestingly in the controls, 11 glutamate and 5 GABA-A receptor genes were more prominently expressed in the caudate than the putamen (fold-increase varied from 1.24 to 2.91). Differences in gene expression patterns between the striatal regions may underlie differences in associated behavioral outputs. Our results suggest an altered balance between caudate-mediated voluntarily controlled and automatic behaviors in alcoholics, including diminished executive control on goal-directed alcohol-seeking behavior.
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| 9. |
- Björklund, Anders, et al.
(författare)
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Neuronal Replacement as a Tool for Basal Ganglia Circuitry Repair : 40 Years in Perspective
- 2020
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Ingår i: Frontiers in Cellular Neuroscience. - : Frontiers Media SA. - 1662-5102. ; 14, s. 146-146
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Forskningsöversikt (refereegranskat)abstract
- The ability of new neurons to promote repair of brain circuitry depends on their capacity to re-establish afferent and efferent connections with the host. In this review article, we give an overview of past and current efforts to restore damaged connectivity in the adult mammalian brain using implants of fetal neuroblasts or stem cell-derived neuronal precursors, with a focus on strategies aimed to repair damaged basal ganglia circuitry induced by lesions that mimic the pathology seen in humans affected by Parkinson's or Huntington's disease. Early work performed in rodents showed that neuroblasts obtained from striatal primordia or fetal ventral mesencephalon can become anatomically and functionally integrated into lesioned striatal and nigral circuitry, establish afferent and efferent connections with the lesioned host, and reverse the lesion-induced behavioral impairments. Recent progress in the generation of striatal and nigral progenitors from pluripotent stem cells have provided compelling evidence that they can survive and mature in the lesioned brain and re-establish afferent and efferent axonal connectivity with a remarkable degree of specificity. The studies of cell-based circuitry repair are now entering a new phase. The introduction of genetic and virus-based techniques for brain connectomics has opened entirely new possibilities for studies of graft-host integration and connectivity, and the access to more refined experimental techniques, such as chemo- and optogenetics, has provided new powerful tools to study the capacity of grafted neurons to impact the function of the host brain. Progress in this field will help to guide the efforts to develop therapeutic strategies for cell-based repair in Huntington's and Parkinson's disease and other neurodegenerative conditions involving damage to basal ganglia circuitry.
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| 10. |
- Bogetofte, Helle, et al.
(författare)
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PARK2 mutation causes metabolic disturbances and impaired survival of human iPSC-derived neurons
- 2019
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Ingår i: Frontiers in Cellular Neuroscience. - : Frontiers Media SA. - 1662-5102. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- The protein parkin, encoded by the PARK2 gene, is vital for mitochondrial homeostasis, and although it has been implicated in Parkinson’s disease (PD), the disease mechanisms remain unclear. We have applied mass spectrometry-based proteomics to investigate the effects of parkin dysfunction on the mitochondrial proteome in human isogenic induced pluripotent stem cell-derived neurons with and without PARK2 knockout (KO). The proteomic analysis quantified nearly 60% of all mitochondrial proteins, 119 of which were dysregulated in neurons with PARK2 KO. The protein changes indicated disturbances in oxidative stress defense, mitochondrial respiration and morphology, cell cycle control, and cell viability. Structural and functional analyses revealed an increase in mitochondrial area and the presence of elongated mitochondria as well as impaired glycolysis and lactate-supported respiration, leading to an impaired cell survival in PARK2 KO neurons. This adds valuable insight into the effect of parkin dysfunction in human neurons and provides knowledge of disease-related pathways that can potentially be targeted for therapeutic intervention.
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| 11. |
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| 12. |
- Borroto-Escuela, Dasiel O., et al.
(författare)
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Understanding the Role of GPCR Heteroreceptor Complexes in Modulating the Brain Networks in Health and Disease
- 2017
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Ingår i: Frontiers in Cellular Neuroscience. - : FRONTIERS MEDIA SA. - 1662-5102. ; 11
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Forskningsöversikt (refereegranskat)abstract
- The introduction of allosteric receptor-receptor interactions in G protein-coupled receptor (GPCR) heteroreceptor complexes of the central nervous system (CNS) gave a new dimension to brain integration and neuropsychopharmacology. The molecular basis of learning and memory was proposed to be based on the reorganization of the homo- and heteroreceptor complexes in the postjunctional membrane of synapses. Long-term memory may be created by the transformation of parts of the heteroreceptor complexes into unique transcription factors which can lead to the formation of specific adapter proteins. The observation of the GPCR heterodimer network (GPCR-HetNet) indicated that the allosteric receptor-receptor interactions dramatically increase GPCR diversity and biased recognition and signaling leading to enhanced specificity in signaling. Dysfunction of the GPCR heteroreceptor complexes can lead to brain disease. The findings of serotonin (5-HT) hetero and isoreceptor complexes in the brain over the last decade give new targets for drug development in major depression. Neuromodulation of neuronal networks in depression via 5-HT, galanin peptides and zinc involve a number of GPCR heteroreceptor complexes in the raphe-hippocampal system: GalR1-5-HT1A, GalR1-5-HT1A-GPR39, GalR1-GalR2, and putative GalR1-GalR2-5-HT1A heteroreceptor complexes. The 5-HT1A receptor protomer remains a receptor enhancing antidepressant actions through its participation in hetero- and homoreceptor complexes listed above in balance with each other. In depression, neuromodulation of neuronal networks in the raphe-hippocampal system and the cortical regions via 5-HT and fibroblast growth factor 2 involves either FGFR1-5-HT1A heteroreceptor complexes or the 5-HT isoreceptor complexes such as 5-HT1A-5-HT7 and 5-HT1A-5-HT2A. Neuromodulation of neuronal networks in cocaine use disorder via dopamine (DA) and adenosine signals involve A2AR-D2R and A2AR-D2R-Sigma1R heteroreceptor complexes in the dorsal and ventral striatum. The excitatory modulation by A2AR agonists of the ventral striato-pallidal GABA anti-reward system via targeting the A2AR-D2R and A2AR-D2R-Sigma1R heteroreceptor complex holds high promise as a new way to treat cocaine use disorders. Neuromodulation of neuronal networks in schizophrenia via DA, adenosine, glutamate, 5-HT and neurotensin peptides and oxytocin, involving A2AR-D2R, D2R-NMDAR, A2AR-D2R-mGluR5, D2R-5-HT2A and D2R-oxytocinR heteroreceptor complexes opens up a new world of D2R protomer targets in the listed heterocomplexes for treatment of positive, negative and cognitive symptoms of schizophrenia.
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| 13. |
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| 14. |
- Busch, Silas E, et al.
(författare)
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Overexpression of the autism candidate gene Cyfip1 pathologically enhances olivo-cerebellar signaling in mice.
- 2023
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Ingår i: Frontiers in cellular neuroscience. - 1662-5102. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Cyfip1, the gene encoding cytoplasmic FMR1 interacting protein 1, has been of interest as an autism candidate gene for years. A potential role in autism spectrum disorder (ASD) is suggested by its location on human chromosome 15q11-13, an instable region that gives rise to a variety of copy number variations associated with syndromic autism. In addition, the CYFIP1 protein acts as a binding partner to Fragile X Messenger Ribonucleoprotein (FMRP) in the regulation of translation initiation. Mutation of FMR1, the gene encoding FMRP, causes Fragile X syndrome, another form of syndromic autism. Here, in mice overexpressing CYFIP1, we study response properties of cerebellar Purkinje cells to activity of the climbing fiber input that originates from the inferior olive and provides an instructive signal in sensorimotor input analysis and plasticity. We find that CYFIP1 overexpression results in enhanced localization of the synaptic organizer neurexin 1 (NRXN1) at climbing fiber synaptic input sites on Purkinje cell primary dendrites and concomitant enhanced climbing fiber synaptic transmission (CF-EPSCs) measured using whole-cell patch-clamp recordings from Purkinje cells in vitro. Moreover, using two-photon measurements of GCaMP6f-encoded climbing fiber signals in Purkinje cells of intact mice, we observe enhanced responses to air puff stimuli applied to the whisker field. These findings resemble our previous phenotypic observations in a mouse model for the human 15q11-13 duplication, which does not extend to the Cyfip1 locus. Thus, our study demonstrates that CYFIP1 overexpression shares a limited set of olivo-cerebellar phenotypes as those resulting from an increased number of copies of non-overlapping genes located on chromosome 15q11-13.
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| 15. |
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| 16. |
- Chen, Y. B., et al.
(författare)
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Inhibitory effects of endomorphin-2 on excitatory synaptic transmission and the neuronal excitability of sacral parasympathetic preganglionic neurons in young rats
- 2015
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Ingår i: Frontiers in Cellular Neuroscience. - : Frontiers Media SA. - 1662-5102. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- The function of the urinary bladder is partly controlled by parasympathetic preganglionic neurons (PPNs) of the sacral parasympathetic nucleus (SPN). Our recent work demonstrated that endomorphin-2 (EM-2)-immunoreactive (IR) terminals form synapses with mu-opioid receptor (MOR)-expressing PPNs in the rat SPN. Here, we examined the effects of EM-2 on excitatory synaptic transmission and the neuronal excitability of the PPNs in young rats (24-30 days old) using a whole-cell patch-clamp approach. PPNs were identified by retrograde labeling with the fluorescent tracer tetramethylrhodamine-dextran (TMR). EM-2 (3 mu M) markedly decreased both the amplitude and the frequency of the spontaneous and miniature excitatory postsynaptic currents (sEPSCs and mEPSCs) of PPNs. EM-2 not only decreased the resting membrane potentials (RMPs) in 61.1% of the examined PPNs with half maximal response at the concentration of 0.282 mu M, but also increased the rheobase current and reduced the repetitive action potential firing of PPNs. Analysis of the current voltage relationship revealed that the EM-2-induced current was reversed at -95 +/- 2.5 mV and was suppressed by perfusion of the potassium channel blockers 4-aminopyridine (4 AP) or BaCl2 or by the addition of guanosine 5'-[beta-thioldiphosphate trilithium salt (GDP-beta-S) to the pipette solution, suggesting the involvement of the G-protein-coupled inwardly rectifying potassium (GIRK) channel. The above EM-2-invoked inhibitory effects were abolished by the MOR selective antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), indicating that the effects of EM-2 on PPNs were mediated by MOR via pre- and/or post-synaptic mechanisms. EM-2 activated pre- and post-synaptic MORs, inhibiting excitatory neurotransmitter release from the presynaptic terminals and decreasing the excitability of PPNs due to hyperpolarization of their membrane potentials, respectively. These inhibitory effects of EM-2 on PPNs at the spinal cord level may explain the mechanism of action of morphine treatment and morphine-induced bladder dysfunction in the clinic.
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| 17. |
- Cheray, M, et al.
(författare)
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Epigenetics Control Microglia Plasticity
- 2018
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Ingår i: Frontiers in cellular neuroscience. - : Frontiers Media SA. - 1662-5102. ; 12, s. 243-
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Tidskriftsartikel (refereegranskat)
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| 18. |
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| 19. |
- Chizhov, Anton V, et al.
(författare)
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Firing clamp : a novel method for single-trial estimation of excitatory and inhibitory synaptic neuronal conductances.
- 2014
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Ingår i: Frontiers in Cellular Neuroscience. - : Frontiers Media SA. - 1662-5102. ; 8:86, s. 86-
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Tidskriftsartikel (refereegranskat)abstract
- Understanding non-stationary neuronal activity as seen in vivo requires estimation of both excitatory and inhibitory synaptic conductances from a single trial of recording. For this purpose, we propose a new intracellular recording method, called "firing clamp." Synaptic conductances are estimated from the characteristics of artificially evoked probe spikes, namely the spike amplitude and the mean subthreshold potential, which are sensitive to both excitatory and inhibitory synaptic input signals. The probe spikes, timed at a fixed rate, are evoked in the dynamic-clamp mode by injected meander-like current steps, with the step duration depending on neuronal membrane voltage. We test the method with perforated-patch recordings from isolated cells stimulated by external application or synaptic release of transmitter, and validate the method with simulations of a biophysically-detailed neuron model. The results are compared with the conductance estimates based on conventional current-clamp recordings.
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| 20. |
- Chu, Xi, et al.
(författare)
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A Novel Major Output Target for Pheromone-Sensitive Projection Neurons in Male Moths
- 2020
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Ingår i: Frontiers in Cellular Neuroscience. - : Frontiers Media SA. - 1662-5102. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Even though insects have comparably small brains, they achieve astoundingly complex behaviors. One example is flying moths tracking minute amounts of pheromones using olfactory circuits. The tracking distance can be up to 1 km, which makes it essential that male moths respond efficiently and reliably to very few pheromone molecules. The male-specific macroglomerular complex (MGC) in the moth antennal lobe contains circuitry dedicated to pheromone processing. Output neurons from this region project along three parallel pathways, the medial, mediolateral, and lateral tracts. The MGC-neurons of the lateral tract are least described and their functional significance is mainly unknown. We used mass staining, calcium imaging, and intracellular recording/staining to characterize the morphological and physiological properties of these neurons in the noctuid moth, Helicoverpa armigera. All lateral-tract MGC neurons targeted the column, a small region within the superior intermediate neuropil. We identified this region as a unique converging site for MGC lateral-tract neurons responsive to pheromones, as well as a dense congregating site for plant odor information since a substantial number of lateral-tract neurons from ordinary glomeruli (OG) also terminates in this region. The lateral-tract MGC-neurons responded with a shorter peak latency than the well-described neurons in the medial tract. Different from the medial-tract MGC neurons encoding odor quality important for species-specific signal identification, those in the lateral tract convey a more robust and rapid signal—potentially important for fast control of hard-wired behavior.
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| 21. |
- Czeh, B., et al.
(författare)
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Long-Term Stress Disrupts the Structural and Functional Integrity of GABAergic Neuronal Networks in the Medial Prefrontal Cortex of Rats
- 2018
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Ingår i: Frontiers in Cellular Neuroscience. - : Frontiers Media SA. - 1662-5102. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Clinical and experimental data suggest that fronto-cortical GABAergic deficits contribute to the pathophysiology of major depressive disorder (MDD). To further test this hypothesis, we used a well characterized rat model for depression and examined the effect of stress on GABAergic neuron numbers and GABA-mediated synaptic transmission in the medial prefrontal cortex (mPFC) of rats. Adult male Wistar rats were subjected to 9-weeks of chronic mild stress (CMS) and based on their hedonic-anhedonic behavior they were behaviorally phenotyped as being stress-susceptible (anhedonic) or stress-resilient. Post mortem quantitative histopathology was used to examine the effect of stress on parvalbumin (PV)-, calretinin- (CR), calbindin- (CB), cholecystokinin- (CCK), somatostatin-(SST) and neuropeptide Y-positive (NPY+) GABAergic neuron numbers in all cortical subareas of the mPFC (anterior cingulate (Cg1), prelimbic (PrL) and infralimbic (IL) cortexes). In vitro, whole-cell patch-clamp recordings from layer II-III pyramidal neurons of the ventral mPFC was used to examine GABAergic neurotransmission. The cognitive performance of the animals was assessed in a hippocampal-prefrontal-cortical circuit dependent learning task. Stress exposure reduced the number of CCK-, CR- and PV-positive GABAergic neurons in the mPFC, most prominently in the IL cortex. Interestingly, in the stress-resilient animals, we found higher number of neuropeptide Y-positive neurons in the entire mPFC. The electrophysiological analysis revealed reduced frequencies of spontaneous and miniature IPSCs in the anhedonic rats and decreased release probability of perisomatic-targeting GABAergic synapses and alterations in GABA(B) receptor mediated signaling. In turn, pyramidal neurons showed higher excitability. Anhedonic rats were also significantly impaired in the object-place paired-associate learning task. These data demonstrate that long-term stress results in functional and structural deficits of prefrontal GABAergic networks. Our findings support the concept that fronto-limbic GABAergic dysfunctions may contribute to emotional and cognitive symptoms of MDD.
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| 22. |
- Derghal, Adel, et al.
(författare)
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Leptin is required for hypothalamic regulation of miRNAs targeting POMC 3'UTR.
- 2015
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Ingår i: Frontiers in Cellular Neuroscience. - : Frontiers Media SA. - 1662-5102. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- The central nervous system (CNS) monitors modifications in metabolic parameters or hormone levels and elicits adaptive responses such as food intake regulation. Particularly, within the hypothalamus, leptin modulates the activity of pro-opiomelanocortin (POMC) neurons which are critical regulators of energy balance. Consistent with a pivotal role of the melanocortin system in the control of energy homeostasis, disruption of the POMC gene causes hyperphagia and obesity. MicroRNAs (miRNAs) are short noncoding RNA molecules that post-transcriptionally repress the expression of genes by binding to 3'-untranslated regions (3'UTR) of the target mRNAs. However, little is known regarding the role of miRNAs that target POMC 3'UTR in the central control energy homeostasis. Particularly, their interaction with the leptin signaling pathway remain unclear. First, we used common prediction programs to search for potential miRNAs target sites on 3'UTR of POMC mRNA. This screening identified a set of conserved miRNAs seed sequences for mir-383, mir-384-3p, and mir-488. We observed that mir-383, mir-384-3p, and mir-488 are up-regulated in the hypothalamus of leptin deficient ob/ob mice. In accordance with these observations, we also showed that mir-383, mir-384-3p, and mir-488 were increased in db/db mice that exhibit a non-functional leptin receptor. The intraperitoneal injection of leptin down-regulated the expression of these miRNAs of interest in the hypothalamus of ob/ob mice showing the involvement of leptin in the expression of mir-383, mir-384-3p, and mir-488. Finally, the evaluation of responsivity to intracerebroventricular administration of leptin exhibited that a chronic treatment with leptin decreased mir-488 expression in hypothalamus of C57BL/6 mice. In summary, these results suggest that leptin modulates the expression of miRNAs that target POMC mRNA in hypothalamus.
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| 23. |
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| 24. |
- Enander, Jonas M.D., et al.
(författare)
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Ubiquitous neocortical decoding of tactile input patterns
- 2019
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Ingår i: Frontiers in Cellular Neuroscience. - : Frontiers Media SA. - 1662-5102. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Whereas functional localization historically has been a key concept in neuroscience, direct neuronal recordings show that input of a particular modality can be recorded well outside its primary receiving areas in the neocortex. Here, we wanted to explore if such spatially unbounded inputs potentially contain any information about the quality of the input received. We utilized a recently introduced approach to study the neuronal decoding capacity at a high resolution by delivering a set of electrical, highly reproducible spatiotemporal tactile afferent activation patterns to the skin of the contralateral second digit of the forepaw of the anesthetized rat. Surprisingly, we found that neurons in all areas recorded from, across all cortical depths tested, could decode the tactile input patterns, including neurons of the primary visual cortex. Within both somatosensory and visual cortical areas, the combined decoding accuracy of a population of neurons was higher than for the best performing single neuron within the respective area. Such cooperative decoding indicates that not only did individual neurons decode the input, they also did so by generating responses with different temporal profiles compared to other neurons, which suggests that each neuron could have unique contributions to the tactile information processing. These findings suggest that tactile processing in principle could be globally distributed in the neocortex, possibly for comparison with internal expectations and disambiguation processes relying on other modalities.
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| 25. |
- Erkenstam, Nina Hellström, 1976, et al.
(författare)
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Temporal Characterization of Microglia/Macrophage Phenotypes in a Mouse Model of Neonatal Hypoxic-Ischemic Brain Injury.
- 2016
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Ingår i: Frontiers in cellular neuroscience. - : Frontiers Media SA. - 1662-5102. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Immune cells display a high degree of phenotypic plasticity, which may facilitate their participation in both the progression and resolution of injury-induced inflammation. The purpose of this study was to investigate the temporal expression of genes associated with classical and alternative polarization phenotypes described for macrophages and to identify related cell populations in the brain following neonatal hypoxia-ischemia (HI). HI was induced in 9-day old mice and brain tissue was collected up to 7 days post-insult to investigate expression of genes associated with macrophage activation. Using cell-markers, CD86 (classic activation) and CD206 (alternative activation), we assessed temporal changes of CD11b(+) cell populations in the brain and studied the protein expression of the immunomodulatory factor galectin-3 in these cells. HI induced a rapid regulation (6 h) of genes associated with both classical and alternative polarization phenotypes in the injured hemisphere. FACS analysis showed a marked increase in the number of CD11b(+)CD86(+) cells at 24 h after HI (+3667%), which was coupled with a relative suppression of CD11b(+)CD206(+) cells and cells that did not express neither CD86 nor CD206. The CD11b(+)CD206(+) population was mixed with some cells also expressing CD86. Confocal microscopy confirmed that a subset of cells expressed both CD86 and CD206, particularly in injured gray and white matter. Protein concentration of galectin-3 was markedly increased mainly in the cell population lacking CD86 or CD206 in the injured hemisphere. These cells were predominantly resident microglia as very few galectin-3 positive cells co-localized with infiltrating myeloid cells in Lys-EGFP-ki mice after HI. In summary, HI was characterized by an early mixed gene response, but with a large expansion of mainly the CD86 positive population during the first day. However, the injured hemisphere also contained a subset of cells expressing both CD86 and CD206 and a large population that expressed neither activation marker CD86 nor CD206. Interestingly, these cells expressed the highest levels of galectin-3 and were found to be predominantly resident microglia. Galectin-3 is a protein involved in chemotaxis and macrophage polarization suggesting a novel role in cell infiltration and immunomodulation for this cell population after neonatal injury.
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