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• 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.

• Thompson, Elise Holter; Lensjø, Kristian Kinden; Wigestrand, Mattis B; Malthe-sørenssen, Anders; Hafting, Torkel & Fyhn, Marianne (2018). Removal of perineuronal nets disrupts recall of a remote fear memory. Proceedings of the National Academy of Sciences of the United States of America (PNAS). ISSN 0027-8424. 115(3), p. 607–612. doi: 10.1073/pnas.1713530115. Full text in Research Archive Show summary

  Throughout life animals learn to recognize cues that signal danger and instantaneously initiate an adequate threat response. Memories of such associations may last a lifetime and far outlast the intracellular molecules currently found to be important for memory processing. The memory engram may be supported by other more stable molecular components, such as the extracellular matrix structure of perineuronal nets (PNNs). Here, we show that recall of remote, but not recent, visual fear memories in rats depend on intact PNNs in the secondary visual cortex (V2L). Supporting our behavioral findings, increased synchronized theta oscillations between V2L and basolateral amygdala, a physiological correlate of successful recall, was absent in rats with degraded PNNs in V2L. Together, our findings suggest a role for PNNs in remote memory processing by stabilizing the neural network of the engram.

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• Lensjø, Kristian Kinden; Rowlands, Daire; Dinh, Tovy; Thompson, Elise Holter; Andrews, Melissa & Hafting, Torkel [Show all 9 contributors for this article] (2018). Conditional knock-out of the Acan gene removes perineuronal nets in adult mice and induces life-long brian plasticity. Full text in Research Archive
• Thompson, Elise Holter; Lensjø, Kristian Kinden; Wigestrand, Mattis B; Hafting, Torkel; Malthe-Sørenssen, Anders & Fyhn, Marianne (2017). The perineuronal nets in the lateral secondary visual cortex are essential for remote visual fear memory. Full text in Research Archive
• Thompson, Elise Holter; Lensjø, Kristian Kinden; Wigestrand, Mattis B; Hafting, Torkel; Fyhn, Marianne & Malthe-Sørenssen, Anders (2016). The perineuronal nets in the lateral secondary visual cortex are essential for remote visual memory. Full text in Research Archive
• Thompson, Elise Holter; Lensjø, Kristian Kinden; Wigestrand, Mattis B; Hafting, Torkel & Fyhn, Marianne (2016). The perineuronal nets in the lateral secondary visual cortex and their impact on remote visual fear memory. Full text in Research Archive

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