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  • 1.
    Case, Laura K
    et al.
    National Center for Complementary and Integrative Health, NIH , Bethesda, Maryland 20892, USA.
    Čeko, Marta
    National Center for Complementary and Integrative Health, NIH , Bethesda, Maryland 20892, USA.
    Gracely, John L
    National Center for Complementary and Integrative Health, NIH , Bethesda, Maryland 20892, USA.
    Richards, Emily A
    National Center for Complementary and Integrative Health, NIH , Bethesda, Maryland 20892, USA.
    Olausson, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Center for Social and Affective Neuroscience (CSAN). Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology.
    Bushnell, M Catherine
    National Center for Complementary and Integrative Health, NIH , Bethesda, Maryland 20892, USA.
    Touch Perception Altered by Chronic Pain and by Opioid Blockade.2016In: eNeuro, E-ISSN 2373-2822, Vol. 3, no 1Article in journal (Refereed)
    Abstract [en]

    Touch plays a significant role in human social behavior and social communication, and its rewarding nature has been suggested to involve opioids. Opioid blockade in monkeys leads to increased solicitation and receipt of grooming, suggesting heightened enjoyment of touch. We sought to study the role of endogenous opioids in perception of affective touch in healthy adults and in patients with fibromyalgia, a chronic pain condition shown to involve reduced opioid receptor availability. The pleasantness of touch has been linked to the activation of C-tactile fibers, which respond maximally to slow gentle touch and correlate with ratings of pleasantness. We administered naloxone to patients and healthy controls to directly observe the consequences of µ-opioid blockade on the perceived pleasantness and intensity of touch. We found that at baseline chronic pain patients showed a blunted distinction between slow and fast brushing for both intensity and pleasantness, suggesting reduced C-tactile touch processing. In addition, we found a differential effect of opioid blockade on touch perception in healthy subjects and pain patients. In healthy individuals, opioid blockade showed a trend toward increased ratings of touch pleasantness, while in chronic pain patients it significantly decreased ratings of touch intensity. Further, in healthy individuals, naloxone-induced increase in touch pleasantness was associated with naloxone-induced decreased preference for slow touch, suggesting a possible effect of opioid levels on processing of C-tactile fiber input. These findings suggest a role for endogenous opioids in touch processing, and provide further evidence for altered opioid functioning in chronic pain patients.

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  • 2.
    Igelström, Kajsa
    et al.
    Princeton Neuroscience Institute and Department of Psychology, Princeton University, Princeton, New Jersey, USA.
    Webb, Taylor
    Princeton Neuroscience Institute and Department of Psychology, Princeton University, Princeton, New Jersey, USA.
    Kelly, YT
    Princeton Neuroscience Institute and Department of Psychology, Princeton University, Princeton, New Jersey, USA.
    Graziano, Michael
    Princeton Neuroscience Institute and Department of Psychology, Princeton University, Princeton, New Jersey, USA.
    Topographical organization of attentional, social and memory processes in the human temporoparietal cortex2016In: eNeuro, E-ISSN 2373-2822, Vol. 3, p. 1-12Article in journal (Refereed)
    Abstract [en]

    The temporoparietal junction (TPJ) is activated in association with a large range of functions, including social cognition, episodic memory retrieval, and attentional reorienting. An ongoing debate is whether the TPJ performs an overarching, domain-general computation, or whether functions reside in domain-specific subdivisions. We scanned subjects with fMRI during five tasks known to activate the TPJ, probing social, attentional, and memory functions, and used data-driven parcellation (independent component analysis) to isolate task-related functional processes in the bilateral TPJ. We found that one dorsal component in the right TPJ, which was connected with the frontoparietal control network, was activated in all of the tasks. Other TPJ subregions were specific for attentional reorienting, oddball target detection, or social attribution of belief. The TPJ components that participated in attentional reorienting and oddball target detection appeared spatially separated, but both were connected with the ventral attention network. The TPJ component that participated in the theory-of-mind task was part of the default-mode network. Further, we found that the BOLD response in the domain-general dorsal component had a longer latency than responses in the domain-specific components, suggesting an involvement in distinct, perhaps postperceptual, computations. These findings suggest that the TPJ performs both domain-general and domain-specific computations that reside within spatially distinct functional components.

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  • 3.
    Larsson, Max
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Broman, Jonas
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Synaptic Organization of VGLUT3 Expressing Low-Threshold Mechanosensitive C Fiber Terminals in the Rodent Spinal Cord2019In: eNeuro, E-ISSN 2373-2822, Vol. 6, no 1Article in journal (Refereed)
    Abstract [en]

    Low-threshold mechanosensitive C fibers (C-LTMRs) that express the vesicular glutamate transporter VGLUT3 are thought to signal affective touch, and may also play a role in mechanical allodynia. However, the nature of the central termination of C-LTMRs in the dorsal horn remains largely unexplored. Here, we used light and electron microscopy in combination with VGLUT3 immunolabeling as a marker of C-LTMR terminations to investigate this issue. VGLUT3+ C-LTMRs formed central terminals of Type II glomeruli in the inner part of lamina II of the dorsal horn, often establishing multiple asymmetric synapses with postsynaptic dendrites but also participating in synaptic configurations with presynaptic axons and dendrites. Unexpectedly, essentially all VGLUT3+ C-LTMR terminals showed substantial VGLUT1 expression in the rat, whereas such terminals in mice lacked VGLUT1. Most VGLUT3+ C-LTMR terminals exhibited weak-to-moderate VGLUT2 expression. Further, C-LTMR terminals formed numerous synapses with excitatory protein kinase C? (PKC?) interneurons and inhibitory parvalbumin neurons, whereas synapses with calretinin neurons were scarce. C-LTMR terminals rarely if ever established synapses with neurokinin 1 receptor (NK1R)-possessing dendrites traversing lamina II. Thus, VGLUT3+ C-LTMR terminals appear to largely correspond to neurofilament-lacking central terminals of Type II glomeruli in inner lamina II and can thus be identified at the ultrastructural level by morphological criteria. The participation of C-LTMR terminals in Type II glomeruli involving diverse populations of interneuron indicates highly complex modes of integration of C-LTMR mediated signaling in the dorsal horn. Furthermore, differences in VGLUT1 expression indicate distinct species differences in synaptic physiology of C-LTMR terminals.

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  • 4.
    Le Moëne, Olivia
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Larsson, Max
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    A New Tool for Quantifying Mouse Facial Expressions2023In: eNeuro, E-ISSN 2373-2822, Vol. 10, no 2Article in journal (Refereed)
    Abstract [en]

    Facial expressions are an increasingly used tool to assess emotional experience and affective state during ex-perimental procedures in animal models. Previous studies have successfully related specific facial features with different positive and negative valence situations, most notably in relation to pain. However, characteriz-ing and interpreting such expressions remains a major challenge. We identified seven easily visualizable facial parameters on mouse profiles, accounting for changes in eye, ear, mouth, snout and face orientation. We monitored their relative position on the face across time and throughout sequences of positive and aversive gustatory and somatosensory stimuli in freely moving mice. Facial parameters successfully captured response profiles to each stimulus and reflected spontaneous movements in response to stimulus valence, as well as contextual elements such as habituation. Notably, eye opening was increased by palatable tastants and innoc-uous touch, while this parameter was reduced by tasting a bitter solution and by painful stimuli. Mouse ear posture appears to convey a large part of emotional information. Facial expressions accurately depicted wel-fare and affective state in a time-sensitive manner, successfully correlating time-dependent stimulation. This study is the first to delineate rodent facial expression features in multiple positive valence situations, including in relation to affective touch. We suggest using this facial expression assay might provide mechanistic insights into emotional expression and improve the translational value of experimental studies in rodents on pain and other states.

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  • 5.
    Ng, Kevin
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Lafee, Odai Waleed Mohammad
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Bouchatta, Otmane
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Makdani, Adarsh D.
    Liverpool John Moores Univ, England.
    Marshall, Andrew G.
    Univ Liverpool, England.
    Olausson, Håkan
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology.
    Mcintyre, Sarah
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Nagi, Saad
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Human Foot Outperforms the Hand in Mechanical Pain Discrimination2024In: eNeuro, E-ISSN 2373-2822, Vol. 11, no 2, article id 0412232024Article in journal (Refereed)
    Abstract [en]

    Tactile discrimination has been extensively studied, but mechanical pain discrimination remains poorly characterized. Here, we measured the capacity for mechanical pain discrimination using a two-alternative forced choice paradigm, with force-calibrated indentation stimuli (Semmes-Weinstein monofilaments) applied to the hand and foot dorsa of healthy human volunteers. In order to characterize the relationship between peripheral nociceptor activity and pain perception, we recorded single-unit activity from myelinated (A) and unmyelinated (C) mechanosensitive nociceptors in the skin using microneurography. At the perceptual level, we found that the foot was better at discriminating noxious forces than the hand, which stands in contrast to that for innocuous force discrimination, where the hand performed better than the foot. This observation of superior mechanical pain discrimination on the foot compared to the hand could not be explained by the responsiveness of individual nociceptors. We found no significant difference in the discrimination performance of either the myelinated or unmyelinated class of nociceptors between skin regions. This suggests the possibility that other factors such as skin biophysics, receptor density or central mechanisms may underlie these regional differences.

  • 6.
    Rusina, Evgeniia
    et al.
    Aix Marseille Univ, France.
    Bernard, Christophe
    Aix Marseille Univ, France.
    Williamson, Adam
    Linköping University, Department of Science and Technology, Laboratory of Organic Electronics. Linköping University, Faculty of Science & Engineering. Aix Marseille Univ, France.
    The Kainic Acid Models of Temporal Lobe Epilepsy2021In: eNeuro, E-ISSN 2373-2822, Vol. 8, no 2, article id 0337-20.2021Article, review/survey (Refereed)
    Abstract [en]

    Experimental models of epilepsy are useful to identify potential mechanisms of epileptogenesis, seizure genesis, comorbidities, and treatment efficacy. The kainic acid (KA) model is one of the most commonly used. Several modes of administration of KA exist, each producing different effects in a strain-, species-, gender-, and age-dependent manner. In this review, we discuss the advantages and limitations of the various forms of KA administration (systemic, intrahippocampal, and intranasal), as well as the histologic, electrophysiological, and behavioral outcomes in different strains and species. We attempt a personal perspective and discuss areas where work is needed. The diversity of KA models and their outcomes offers researchers a rich palette of phenotypes, which may be relevant to specific traits found in patients with temporal lobe epilepsy.

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  • 7.
    Sikora, Magdalena
    et al.
    Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences , 31-343 Krakow, Poland.
    Tokarski, Krzysztof
    Department of Physiology, Institute of Pharmacology, Polish Academy of Sciences , 31-343 Krakow, Poland..
    Bobula, Bartosz
    Department of Physiology, Institute of Pharmacology, Polish Academy of Sciences , 31-343 Krakow, Poland..
    Zajdel, Joanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Jastrzębska, Kamila
    Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences , 31-343 Krakow, Poland.
    Cieślak, Przemysław Eligiusz
    Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences , 31-343 Krakow, Poland.
    Zygmunt, Magdalena
    Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences , 31-343 Krakow, Poland.
    Sowa, Joanna
    Department of Physiology, Institute of Pharmacology, Polish Academy of Sciences , 31-343 Krakow, Poland..
    Smutek, Magdalena
    Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences , 31-343 Krakow, Poland.
    Kamińska, Katarzyna
    Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences , 31-343 Krakow, Poland.
    Gołembiowska, Krystyna
    Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences , 31-343 Krakow, Poland.
    Engblom, David
    Linköping University, Center for Social and Affective Neuroscience (CSAN). Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Hess, Grzegorz
    Department of Physiology, Institute of Pharmacology, Polish Academy of Sciences , 31-343 Krakow, Poland..
    Przewlocki, Ryszard
    Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, 31-343 Krakow, Poland; Department of Neurobiology and Neuropsychology, Institute of Applied Psychology, Jagiellonian University, 30-348 Krakow, Poland.
    Rodriguez Parkitna, Jan
    Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences , 31-343 Krakow, Poland.
    NMDA Receptors on Dopaminoceptive Neurons Are Essential for Drug-Induced Conditioned Place Preference.2016In: eNeuro, E-ISSN 2373-2822, Vol. 3, no 3, article id ENEURO.0084-15.2016Article in journal (Refereed)
    Abstract [en]

    Plasticity of the brain's dopamine system plays a crucial role in adaptive behavior by regulating appetitive motivation and the control of reinforcement learning. In this study, we investigated drug- and natural-reward conditioned behaviors in a mouse model in which the NMDA receptor-dependent plasticity of dopaminoceptive neurons was disrupted. We generated a transgenic mouse line with inducible selective inactivation of the NR1 subunit in neurons expressing dopamine D1 receptors (the NR1(D1CreERT2) mice). Whole-cell recordings of spontaneous EPSCs on neurons in the nucleus accumbens confirmed that a population of neurons lacked the NMDA receptor-dependent component of the current. This effect was accompanied by impaired long-term potentiation in the nucleus accumbens and in the CA1 area of the ventral, but not the dorsal, hippocampus. Mutant mice did not differ from control animals when tested for pavlovian or instrumental conditioning. However, NR1(D1CreERT2) mice acquired no preference for a context associated with administration of drugs of abuse. In the conditioned place preference paradigm, mutant mice did not spend more time in the context paired with cocaine, morphine, or ethanol, although these mice acquired a preference for sucrose jelly and an aversion to naloxone injections, as normal. Thus, we observed that the selective inducible ablation of the NMDA receptors specifically blocks drug-associated context memory with no effect on positive reinforcement in general.

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