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• 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.

• 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.

• Pettersen, Markus; Rogge, Frederik & Lepperød, Mikkel (2024). Search Learning Place Cell Representations and Context-Dependent Remapping. Advances in Neural Information Processing Systems. ISSN 1049-5258. Full text in Research Archive
• 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.

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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. Full text in Research Archive
• Pettersen, Markus Borud; Rogge, Frederik Sebastian & Lepperød, Mikkel Elle (2024). Learning place cell representations and context-dependent remapping. doi: https:/neurips.cc/virtual/2024/poster/96470. Full text in Research Archive Show summary

  Hippocampal place cells are known for their spatially selective firing patterns, which has led to the suggestion that they encode an animal's location. However, place cells also respond to contextual cues, such as smell. Furthermore, they have the ability to remap, wherein the firing fields and rates of cells change in response to changes in the environment. How place cell responses emerge, and how these representations remap is not fully understood. In this work, we propose a similarity-based objective function that translates proximity in space, to proximity in representation. We show that a neural network trained to minimize the proposed objective learns place-like representations. We also show that the proposed objective is easily extended to include other sources of information, such as context information, in the same way. When trained to encode multiple contexts, networks learn distinct representations, exhibiting remapping behaviors between contexts. The proposed objective is invariant to orthogonal transformations. Such transformations of the original trained representation (e.g. rotations), therefore yield new representations distinct from the original, without explicit relearning, akin to remapping. Our findings shed new light on the formation and encoding properties of place cells, and also demonstrate an interesting case of representational reuse.

• 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
• Rogge, Frederik; Malthe-Sørenssen, Anders; Fyhn, Marianne & Lepperød, Mikkel (2022). On the Structural Sensitivity of the Successor Representation. Full text in Research Archive
• 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. Full text in Research Archive Show summary

  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.

• Rogge, Frederik Sebastian; Fyhn, Marianne; Malthe-Sørenssen, Anders; Lepperød, Mikkel Elle & Lensjø, Kristian (2026). Normative and Experimental Analyses of Learning-Dependent Representations in the Hippocampal-Parahippocampal System. Universitetet i Oslo. Full text in Research Archive Show summary

  The brain is thought to build a cognitive map of both physical and abstract spaces, helping us navigate the world, organize knowledge, and form new memories. In this thesis, I investigated key brain subregions to uncover the principles underlying the emergence of neural representations. I focused on the general properties of the neural code, how visual inputs are integrated, and how these representations reorganize through learning. To address these questions, I combined large-scale chronic two-photon calcium imaging in mice with normative modeling in artificial neural networks. We show that neurons in the medial entorhinal cortex (MEC) develop task-relevant tuning during learning of a purely visual association task, pointing to a broader role beyond its classical link to spatial coding. In parallel, selective disruption of specific neuron types in the postrhinal cortex (POR) impaired learning of the same task, demonstrating their causal contribution. Furthermore, using artificial neural networks, we uncovered computational principles governing how spatial representations emerge and transform. Finally, we revealed dissociable contributions of POR and MEC to visually guided navigation, highlighting their distinct roles. Together, these results shed new light on the emergence of neural representations in different brain regions and their transformation through learning.

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