Ingeborg Nymoen

• Nymoen, Ingeborg; Rogge, Frederik Sebastian; Aasen, Anna Hjertvik; Grødem, Sverre; Malthe-Sørenssen, Anders & Lepperød, Mikkel Elle [Vis alle 9 forfattere av denne artikkelen] (2026). Task and Behavior-Related Variables Are Encoded by the Postrhinal and Medial Entorhinal Cortex During Non-Spatial Associative Learning. eLIFE. 14. doi: 10.7554/elife.106095.1. Fulltekst i vitenarkiv Vis sammendrag

  The medial entorhinal cortex (MEC) is pivotal in spatial computations and episodic memory. In particular, an animal’s position can be decoded from the activity of entorhinal grid cells. However, it remains elusive whether MEC could play a more general role in different types of associative learning and how the representations develop during the learning process. It has been shown that the postrhinal cortex (POR), which is directly connected to MEC, integrates visual stimuli with salient outcomes. Here, we use a non-spatial visual association task to investigate whether MEC neurons represent low-level visual cues during learning. Using a Go/NoGo visual association task, we recorded neural activity in MEC and POR throughout the learning phase as mice associated drifting gratings with rewarded, aversive, or neutral outcomes. Our findings reveal that the neural tuning curves in both the POR and MEC change with the learning of the task. From the start of training, the POR neurons exhibited response tuning to the visual cues, and the tuning was stable to cue orientations during learning. In contrast, MEC neurons did not initially respond very strongly to visual cues but developed a robust tuning toward the rewarded trials. While the MEC’s representation of visual information was limited, it encoded other task elements. A large fraction of the neurons formed distinct functional clusters that were either activated or suppressed by reward-related behavior. Remarkably, these clusters segregated anatomically in MEC and maintained strong within-cluster correlations before and after training. Notably, although the same functional clusters were apparent in the POR, they did not show any anatomical structure as in the MEC. Task reversal induced significant changes in network responses across both regions, with a decrease in overall task-responsive neurons but a slight increase in stimulus representation. Strikingly, information about the choice to lick emerged with learning in both brain areas, and most significantly within the functional cell clusters representing reward consumption and plus-cue stimulus. Our results demonstrate that although neurons in MEC and POR develop behavior-modulated tuning during learning of a non-spatial visual association task, the MEC exhibits stronger within-cluster correlations and anatomical organization. Conversely, the POR population exhibits less structural organization and more specific stimulus-tuning, which is reflective of being a higher visual association area. Our findings reveal that the MEC can encode task– and behavior-related variables beyond spatial information.

• Grødem, Sverre; Thompson, Elise Holter; Røe, Malin Benum; Vatne, Guro Helén; Nymoen, Ingeborg & Buccino, Alessio Paolo [Vis alle 10 forfattere av denne artikkelen] (2025). Differential impacts of germline and adult aggrecan knockout in PV+ neurons on perineuronal nets and PV+ neuronal function. Molecular Psychiatry. ISSN 1359-4184. 30, s. 2907–2921. doi: 10.1038/s41380-025-02894-5. Fulltekst i vitenarkiv Vis sammendrag

  Perineuronal nets (PNNs) are a condensed form of extracellular matrix primarily found around parvalbumin-expressing (PV+) interneurons. The postnatal maturation of PV+ neurons is accompanied with the formation of PNNs and reduced plasticity. Alterations in PNN and PV+ neuron function have been described for mental disorders such as schizophrenia and autism. The formation of PNNs is highly dependent on aggrecan, a proteoglycan encoded by the ACAN gene, but it remains unknown if it is produced by the PV+ neurons themselves. Thus, we established a knockout (KO) mouse model (ACANflx/PVcre) and an adeno-associated virus to specifically eliminate aggrecan production from PV+ neurons, in the germline or adult animals, respectively. The germline KO (ACANflx/PVcre) eliminated the expression of PNNs labeled by Wisteria floribunda agglutinin (WFA), the most commonly used PNN marker. Surprisingly, electrophysiological properties of PV+ interneurons and ocular dominance plasticity of adult ACANflx/PVcre mice were similar to controls. In contrast, AAV-mediated ACAN knockout in adult mice increased ocular dominance plasticity. Moreover, in vivo Chondroitinase ABC treatment of KO mice resulted in reduced firing rate of PV+ cells and increased frequency of spontaneous excitatory postsynaptic currents (sEPSC), a phenotype associated with chABC treatment of WT animals. These findings suggest that compensatory mechanisms may be activated during development in response to the germline loss of aggrecan. Indeed, qPCR of bulk tissue indicates that other PNN components, including neurocan and tenascin-R, are expressed at higher levels in the KO animals. Finally, behavioral testing revealed that ACANflx/PVcre mice had similar long-term memory as controls in the Morris water maze. However, they employed bolder search strategies during spatial learning and showed lower level of anxiety-related behavior in an open field and zero maze.

• Lensjø, Kristian; Nymoen, Ingeborg; Rogge, Frederik Sebastian; Tøndel, Kristin; Sugden, Arthur & Shurnayte, Inga [Vis alle 11 forfattere av denne artikkelen] (2025). Local inhibitory circuits mediate cortical reactivations and memory consolidation. Science Advances. 11(22), s. 1–14. doi: 10.1126/sciadv.adu9800. Fulltekst i vitenarkiv Vis sammendrag

  Highly salient events activate neurons across various brain regions. During subsequent rest or sleep, the activity patterns of these neurons often correlate with those observed during the preceding experience. Growing evidence suggests that these reactivations play a crucial role in memory consolidation, the process by which experiences are solidified in cortical networks for long-term storage. Here, we use longitudinal two-photon Ca2+ imaging alongside paired LFP recordings in the hippocampus and cortex, to show that targeted manipulation of PV+ inhibitory neurons in the lateral visual cortex after daily training selectively attenuates cue-specific reactivations and learning, with only minute effects on spontaneous activity and no apparent effect on normal function such as visual cue–elicited responses during training. In control mice, reactivations were biased toward salient cues, persisted for hours after training had ended, and the prevalence of reactivations was aligned with the learning process. Overall, our results underscore a crucial role for cortical reactivations in memory consolidation.

• Rajalingam, Dhaksshaginy; Nymoen, Ingeborg; Nyberg, Henriette; Nielsen, Morten Birkeland; Einarsen, Ståle Valvatne & Gjerstad, Johannes (2021). Workplace bullying increases the risk of anxiety through a stress-induced β2-adrenergic receptor mechanism: a multisource study employing an animal model, cell culture experiments and human data. International Archives of Occupational and Environmental Health. ISSN 0340-0131. 94, s. 1905–1915. doi: 10.1007/s00420-021-01718-7. Fulltekst i vitenarkiv Vis sammendrag

  Objectives Several studies show that severe social stressors, e.g., in the form of exposure to workplace bullying in humans, is associated with negative mental health effects such as depression and anxiety among those targeted. However, the understanding of the underlying biological mechanisms that may explain the relationship between exposure to bullying and such negative health outcomes is scarce. The analyses presented here focus on understanding the role of the β2-adrenergic receptors (ADRB2) on this association. Methods First, a resident-intruder paradigm was used to investigate changes in circulating norepinephrine (NE) in rat serum induced by repeated social defeat and its relationship with subsequent social behavior. Second, the direct effects of the stress-hormones NE and cortisol, i.e., synthetic dexamethasone (DEX), on the ADRB2 expression (qPCR) and monocyte chemoattractant protein-1 (MCP-1) release (immunoassay) was examined in cultured EL-1 cells. Third, in a probability sample of 1052 Norwegian employees, the 9-item short version of the Negative Acts Questionnaire—Revised (S-NAQ) inventory, Hopkins Symptom Checklist and genotyping (SNP TaqMan assay) were used to examine the association between social stress in the form of workplace bullying and anxiety moderated by the ADRB2 genotype (rs1042714) in humans. Results The present study showed a clear association between reduced social interaction and increased level of circulating NE in rats previously exposed to repeated social defeat. Parallel cell culture work, which was performed to examine the direct effects of NE and DEX on ADRB2, demonstrated ADRB2 downregulation and MCP-1 upregulation in cultured EL-1 cells. Genotyping with regard to the ADRB2 genotype; rs1042714 CC vs CG/GG, on human saliva samples, showed that individuals with CC reported more anxiety following exposure to bullying behaviors as compared to the G carriers. Conclusion We conclude that workplace bullying promotes anxiety and threaten well-being through an ADRB2 associated mechanism.

• Rajalingam, Dhaksshaginy; Nymoen, Ingeborg; Jacobsen, Daniel Pitz; Eriksen, Mina Baarnes; Dissen, Erik & Nielsen, Morten Birkeland [Vis alle 8 forfattere av denne artikkelen] (2020). Repeated social defeat promotes persistent inflammatory changes in splenic myeloid cells; decreased expression of β-arrestin-2 (ARRB2) and increased expression of interleukin-6 (IL-6). BMC Neuroscience. 21:25. doi: 10.1186/s12868-020-00574-4. Fulltekst i vitenarkiv Vis sammendrag

  Background Previous studies suggest that persistent exposure to social stress in mammals may be associated with multiple physiological effects. Here, we examine the effects of social stress in rats, i.e. repeated social defeat, on behavior, hypothalamic–pituitary–adrenal (HPA)-axis and immune system. Methods A resident-intruder paradigm, where an intruder rat was exposed to social stress by a dominant resident rat for 1 hour each day for 7 consecutive days was used. The day after the last stress exposure in the paradigm the data were analyzed. Variation in social interaction was observed manually, whereas locomotion was analyzed off-line by a purpose-made software. Gene expression in the pituitary gland, adrenal gland and myeloid cells isolated from the spleen was measured by qPCR. Results The exposure to social stress induced decreased weight gain and increased locomotion. An increased nuclear receptor subfamily group C number 1 (NR3C1) expression in the pituitary gland was also shown. In myeloid cells harvested from the spleen, we observed decreased expression of the β2-adrenergic receptor (ADRB2) and β-arrestin-2 (ARRB2), but increased expression of interleukin-6 (IL-6). Subsequent analyses in the same cells showed that ARRB2 was negatively correlated with IL-6 following the stress exposure. Conclusion Our results show that that the experience of social stress in the form of repeated social defeat in rats is a potent stressor that in myeloid cells in the spleen promotes persistent inflammatory changes. Future research is needed to examine whether similar inflammatory changes also can explain the impact of social stress, such as bullying and harassment, among humans.

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• Rogge, Frederik Sebastian; Lensjø, Kristian; Nymoen, Ingeborg; Grødem, Sverre & Fyhn, Marianne (2025). Visual cue representations in the postrhinal and medial entorhinal cortex during spatial navigation. Fulltekst i vitenarkiv
• Nymoen, Ingeborg; Rogge, Frederik Sebastian; Grødem, Sverre; Lepperød, Mikkel Elle; Hafting, Torkel & Lensjø, Kristian [Vis alle 7 forfattere av denne artikkelen] (2024). Visual associative learning in the medial entorhinal cortex. Fulltekst i vitenarkiv
• Rogge, Frederik Sebastian; Nymoen, Ingeborg; Lepperød, Mikkel Elle; Hafting, Torkel; Fyhn, Marianne & Lensjø, Kristian (2022). Learning flexibility in parahippocampal networks. doi: https:/fensforum.org/wp-content/uploads/2023/01/FENS2022.pdf. Fulltekst i vitenarkiv Vis sammendrag

  Mammals show remarkable flexibility of behaviors, and have the ability to abstract specific rules and learning sets into generalized low dimensional structures that can be applied in new conditions. Recent work suggests that this generalization could take place in parahippocampal regions, in particular in the entorhinal cortex (EC). Here, the medial part (MEC) seems to extract the structure of state space irrespective of modality (e.g. spatial or sound). The lateral part (LEC) receives input about complex features of objects and multimodal sensory information from association cortices, including the postrhinal cortex (POR). This puts the EC in a unique position to function as an integration center for higher order representations. To investigate the role of the entorhinal cortex in abstracting and generalizing task content, we have established a set of simple association tasks for mice that enable both rule switching and change of sensory modality. We train mice in these tasks over multiple sessions and record large neuronal populations in the EC during and after training using two-photon imaging. To this end, we utilize custom right-angle prism assemblies that cover either the MEC, or POR and LEC. We hypothesize that both MEC and LEC will display learning-induced changes in the low dimensional neural representations over time, with consistent structures that are used and transferred across different tasks. Our preliminary data from mice trained in a visual association task indicate that neurons in both regions develop representations of task structure with training.

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