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• Lepperød, Mikkel Elle; Christensen, Ane Charlotte; Lensjø, Kristian Kinden; Buccino, Alessio Paolo; Yu, Jai & Fyhn, Marianne [Show all 7 contributors for this article] (2021). Optogenetic pacing of medial septum parvalbumin-positive cells disrupts temporal but not spatial firing in grid cells. Science Advances. 7(19). doi: 10.1126/sciadv.abd5684. Full text in Research Archive Show summary

  Grid cells in the medial entorhinal cortex (MEC) exhibit remarkable spatial activity patterns with spikes coordinated by theta oscillations driven by the medial septal area (MSA). Spikes from grid cells progress relative to the theta phase in a phenomenon called phase precession, which is suggested as essential to create the spatial periodicity of grid cells. Here, we show that optogenetic activation of parvalbumin-positive (PV+) cells in the MSA enabled selective pacing of local field potential (LFP) oscillations in MEC. During optogenetic stimulation, the grid cells were locked to the imposed pacing frequency but kept their spatial patterns. Phase precession was abolished, and speed information was no longer reflected in the LFP oscillations but was still carried by rate coding of individual MEC neurons. Together, these results support that theta oscillations are not critical to the spatial pattern of grid cells and do not carry a crucial velocity signal.

• Christensen, Ane Charlotte; Lensjø, Kristian Kinden; Lepperød, Mikkel Elle; Dragly, Svenn-Arne; Sutterud, Hallvard & Blackstad, Jan Sigurd [Show all 8 contributors for this article] (2021). Perineuronal nets stabilize the grid cell network. Nature Communications. 12. doi: 10.1038/s41467-020-20241-w. Full text in Research Archive Show summary

  Grid cells are part of a widespread network which supports navigation and spatial memory. Stable grid patterns appear late in development, in concert with extracellular matrix aggregates termed perineuronal nets (PNNs) that condense around inhibitory neurons. It has been suggested that PNNs stabilize synaptic connections and long-term memories, but their role in the grid cell network remains elusive. We show that removal of PNNs leads to lower inhibitory spiking activity, and reduces grid cells’ ability to create stable representations of a novel environment. Furthermore, in animals with disrupted PNNs, exposure to a novel arena corrupted the spatiotemporal relationships within grid cell modules, and the stored representations of a familiar arena. Finally, we show that PNN removal in entorhinal cortex distorted spatial representations in downstream hippocampal neurons. Together this work suggests that PNNs provide a key stabilizing element for the grid cell network.

• Christensen, Ane Charlotte; Lepperød, Mikkel; Lensjø, Kristian Kinden; Dragly, Svenn-Arne; Blackstad, Jan Sigurd Beddari & Fyhn, Marianne [Show all 7 contributors for this article] (2019). Perineuronal nets stabilize the grid cell network. BioRxiv. ISSN 0362-4331. doi: 10.1101/796342. Full text in Research Archive
• Lensjø, Kristian Kinden; Christensen, Ane Charlotte; Tennøe, Simen; Fyhn, Marianne & Hafting, Torkel (2017). Differential Expression and Cell-Type Specificity of Perineuronal Nets in Hippocampus, Medial Entorhinal Cortex and Visual Cortex Examined in the Rat and Mouse. eNeuro. 4(3), p. 1–18. doi: 10.1523/ENEURO.0379-16.2017. Full text in Research Archive Show summary

  Perineuronal nets (PNNs) are specialized extracellular matrix (ECM) structures that condense around the soma and proximal dendrites of subpopulations of neurons. Emerging evidence suggests that they are involved in regulating brain plasticity. However, the expression of PNNs varies between and within brain areas. A lack of quantitative studies describing the distribution and cell-specificity of PNNs makes it difficult to reveal the functional roles of PNNs. In the current study, we examine the distribution of PNNs and the identity of PNN-enwrapped neurons in three brain areas with different cognitive functions: the dorsal hippocampus, medial entorhinal cortex (mEC) and primary visual cortex (V1). We compared rats and mice as knowledge from these species are often intermingled. The most abundant expression of PNNs was found in the mEC and V1, while dorsal hippocampus showed strikingly low levels of PNNs, apart from dense expression in the CA2 region. In hippocampus we also found apparent species differences in expression of PNNs. While we confirm that the PNNs enwrap parvalbumin-expressing (PV+) neurons in V1, we found that they mainly colocalize with excitatory CamKII-expressing neurons in CA2. In mEC, we demonstrate that in addition to PV+ cells, the PNNs colocalize with reelin-expressing stellate cells. We also show that the maturation of PNNs in mEC coincides with the formation of grid cell pattern, while PV+ cells, unlike in other cortical areas, are present from early postnatal development. Finally, we demonstrate considerable effects on the number of PSD-95-gephyrin puncta after enzymatic removal of PNNs.

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• Thon, Sarah Kriebel; Olsen, Elise Reppe; Fjeldstad, Maria Perona; Schøyen, Vemund Sigmundson; Lepperød, Mikkel Elle & Christensen, Ane Charlotte [Show all 8 contributors for this article] (2024). Social and spatial codes in the hippocampus. 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
• Thon, Sarah Kriebel; Christensen, Ane Charlotte; Fjeldstad, Maria P; Schøyen, Vemund Sigmundson; Olsen, Elise Reppe & Lepperød, Mikkel Elle [Show all 8 contributors for this article] (2022). Social and spatial codes in hippocampus CA2 and entorhinal cortex. Full text in Research Archive
• Christensen, Ane Charlotte; Lensjø, Kristian Kinden; Lepperød, Mikkel Elle; Fyhn, Marianne & Hafting, Torkel (2017). The role of extracellular matrix molecules for spatial representations in medial entorhinal cortex. Full text in Research Archive
• Christensen, Ane Charlotte; Fyhn, Marianne & Hafting, Torkel (2017). The role of perineuronal nets in spatial representations. Full text in Research Archive
• Blackstad, Jan Sigurd; Christensen, Ane Charlotte; Lensjø, Kristian Kinden; Hafting, Torkel & Fyhn, Marianne (2016). Involvement of perineuronal nets in spatial information transfer between the entorhinal cortex and hippocampus. Full text in Research Archive
• Blackstad, Jan Sigurd; Christensen, Ane Charlotte; Lensjø, Kristian Kinden; Hafting, Torkel & Fyhn, Marianne (2016). Involvement of perineuronal nets in spatial information transfer between the entorhinal cortex and hippocampus. Full text in Research Archive
• Lepperød, Mikkel Elle; Lensjø, Kristian Kinden; Christensen, Ane Charlotte; Fyhn, Marianne; Hafting, Torkel & Einevoll, Gaute (2015). Building an entorhinal cortex network. Full text in Research Archive
• Christensen, Ane Charlotte; Lensjø, Kristian Kinden; Lepperød, Bjørn Mikkel Elle; Fyhn, Marianne & Hafting, Torkel (2015). The role of extracellular matrix molecules for spatial representations and plasticity in entorhinal cortex. Full text in Research Archive
• Hafting, Torkel; Lensjø, Kristian Kinden; Christensen, Ane Charlotte; Dick, Gunnar & Fyhn, Marianne (2014). Perineuronal nets, plasticity and information-processing in visual cortex, medial entorhinal cortex and hippocampus. Full text in Research Archive

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