Sverre Grødem

• Essner, Rachel A.; Ruda, Kiersten; Choh, Hannah J.; Kucukdereli, Hakan; Amsalem, Oren & Edelhaus, Julia [Show all 11 contributors for this article] (2026). Brainstem sensing of multiple body signals during food consumption. Neuron. ISSN 0896-6273. doi: 10.1016/j.neuron.2026.08.015. Full text in Research Archive
• Nymoen, Ingeborg; Rogge, Frederik Sebastian; Aasen, Anna Hjertvik; Grødem, Sverre; Malthe-Sørenssen, Anders & Lepperød, Mikkel Elle [Show all 9 contributors for this article] (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. Full text in Research Archive Show summary

  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 [Show all 10 contributors for this article] (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, p. 2907–2921. doi: 10.1038/s41380-025-02894-5. Full text in Research Archive Show summary

  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 [Show all 11 contributors for this article] (2025). Local inhibitory circuits mediate cortical reactivations and memory consolidation. Science Advances. 11(22), p. 1–14. doi: 10.1126/sciadv.adu9800. Full text in Research Archive Show summary

  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.

• Hanssen, Kine Ødegård; Grødem, Sverre; Fyhn, Marianne; Hafting, Torkel; Einevoll, Gaute & Ness, Torbjørn V [Show all 7 contributors for this article] (2023). Responses in fast-spiking interneuron firing rates to parameter variations associated with degradation of perineuronal nets. Journal of Computational Neuroscience. ISSN 0929-5313. 51, p. 283–298. doi: 10.1007/s10827-023-00849-9. Full text in Research Archive Show summary

  The perineuronal nets (PNNs) are sugar coated protein structures that encapsulate certain neurons in the brain, such as parvalbumin positive (PV) inhibitory neurons. As PNNs are theorized to act as a barrier to ion transport, they may effectively increase the membrane charge-separation distance, thereby affecting the membrane capacitance. Tewari et al. (2018) found that degradation of PNNs induced a 25%-50% increase in membrane capacitance cm and a reduction in the firing rates of PV-cells. In the current work, we explore how changes in cm affects the firing rate in a selection of computational neuron models, ranging in complexity from a single compartment Hodgkin-Huxley model to morphologically detailed PV-neuron models. In all models, an increased cm lead to reduced firing, but the experimentally reported increase in cm was not alone sufficient to explain the experimentally reported reduction in firing rate. We therefore hypothesized that PNN degradation in the experiments affected not only cm, but also ionic reversal potentials and ion channel conductances. In simulations, we explored how various model parameters affected the firing rate of the model neurons, and identified which parameter variations in addition to cm that are most likely candidates for explaining the experimentally reported reduction in firing rate.

• Grødem, Sverre; Nymoen, Ingeborg; Vatne, Guro Helén; Rogge, Frederik Sebastian; Björnsdottir, Valgerdur & Lensjø, Kristian [Show all 7 contributors for this article] (2023). An updated suite of viral vectors for in vivo calcium imaging using intracerebral and retro-orbital injections in male mice. Nature Communications. 14(1), p. 608–1. doi: 10.1038/s41467-023-36324-3. Full text in Research Archive Show summary

  Abstract Genetically encoded Ca 2+ indicators (GECIs) are widely used to measure neural activity. Here, we explore the use of systemically administered PHP.eB AAVs for brain-wide expression of GECIs and compare the expression properties to intracerebrally injected AAVs in male mice. We show that systemic administration is a promising strategy for imaging neural activity. Next, we establish the use of EE-RR- (soma) and RPL10a (Ribo) soma-targeting peptides with the latest jGCaMP and show that EE-RR-tagged jGCaMP8 gives rise to strong expression but limited soma-targeting. In contrast, Ribo-tagged jGCaMP8 lacks neuropil signal, but the expression rate is reduced. To combat this, we modified the linker region of the Ribo-tag (RiboL1-). RiboL1-jGCaMP8 expresses faster than Ribo-jGCaMP8 but remains too dim for reliable use with systemic virus administration. However, intracerebral injections of the RiboL1-tagged jGCaMP8 constructs provide strong Ca 2+ signals devoid of neuropil contamination, with remarkable labeling density.

• Hanssen, Kine Ødegård; Grødem, Sverre; Fyhn, Marianne; Hafting, Torkel; Einevoll, Gaute & Ness, Torbjørn Vefferstad [Show all 7 contributors for this article] (2022). Effects of perineuronal nets on neural ring properties. Research Square. ISSN 2693-5015. doi: 10.21203/rs.3.rs-2198467/v1. Full text in Research Archive
• Eriksen, Maria Steene; Nikolaienko, Oleksii; Hallin, Erik Ingmar; Grødem, Sverre; Johannessen, Helene Bustad & Flydal, Marte Innselset [Show all 23 contributors for this article] (2020). Arc self‐association and formation of virus‐like capsids are mediated by an N‐terminal helical coil motif. The FEBS Journal. ISSN 1742-464X. doi: 10.1111/febs.15618. Full text in Research Archive
• Hallin, Erik Ingmar; Eriksen, Maria Steene; Baryshnikov, Sergei; Nikolaienko, Oleksii; Grødem, Sverre & Hosokawa, Tomohisa [Show all 9 contributors for this article] (2018). Structure of monomeric full‐length ARC sheds light on molecular flexibility, protein interactions, and functional modalities. Journal of Neurochemistry. ISSN 0022-3042. 147(3), p. 323–343. doi: 10.1111/jnc.14556. Full text in Research Archive

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• Kleven, Tina; Grødem, Sverre; Ciosk, Rafal & Fyhn, Marianne (2025). Temperature-dependent neuronal plasticity in a mouse model of induced hypothermia. Full text in Research Archive
• 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. Full text in Research Archive
• Nymoen, Ingeborg; Rogge, Frederik Sebastian; Grødem, Sverre; Lepperød, Mikkel Elle; Hafting, Torkel & Lensjø, Kristian [Show all 7 contributors for this article] (2024). Visual associative learning in the medial entorhinal cortex. Full text in Research Archive
• Fjeldstad, Maria Perona; Lepperød, Mikkel Elle; Schøyen, Vemund Sigmundson; Christensen, Ane Charlotte; Grødem, Sverre & Fyhn, Marianne [Show all 7 contributors for this article] (2024). Theta modulation of grid cells in the medial entorhinal cortex in a novel environment task. Full text in Research Archive
• Grødem, Sverre; Sandvik, Guro Katrine; Hazen, Jennifer; Lensjø, Kristian Kinden; Hafting, Torkel & Fyhn, Marianne (2018). A CRISPR-Cas9 platform for genetic perturbations of brain extracellular matrix regulators in vivo. Full text in Research Archive

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