Sammendrag
The brain possesses an astounding ability to acquire new memories and retain these memories throughout our lifespan. Consequently, neuronal networks in the brain must exhibit flexibility, or plasticity, adapting and strengthening neuronal connections in response to new learning. Simultaneously, the brain must maintain sufficient stability to solidify the neural connections that underpin long-term memory. The lattice-like structures known as Perineuronal Nets (PNNs), which mainly surround a subset of inhibitory interneurons in the cerebral cortex, are believed to dampen brain plasticity, thus facilitating long-term information retention. In this thesis, I perturb the PNNs by genetically knocking out the PNN component aggrecan solely in these interneurons. Through electrophysiological and behavioral assays and computational modeling, I investigate the potential effects of this perturbation. My findings indicate that while removing aggrecan in developing subjects eliminates PNNs without affecting interneuron function, its removal in adults significantly alters plasticity, suggesting that compensatory mechanisms may mitigate the effect of losing aggrecan and thus PNNs in the germline. These insights shed light on the intricate mechanisms behind memory formation and maintenance in the brain and could contribute to understanding or developing treatments for diseases of the brain, such as Alzheimer's disease. Finally, I develop soma-targeted, genetically-encoded calcium indicator constructs that allow for precise measurement of neuronal activity at the single-cell level in live animals.
Artikkelliste
Paper I. Sverre Grødem, Elise H. Thompson, Malin B. Røe, Guro H. Vatne, Ingeborg Nymoen, Alessio Buccino, Tarjei Madland, Torkel Hafting, Marianne Fyhn, Kristian K. Lensjø. Deciphering the Role of Aggrecan in Parvalbumin Interneurons: Unexpected Outcomes from a Conditional ACAN Knockout That Eliminates WFA+ Perineuronal nets. To be published. The paper is not available in DUO awaiting publishing. |
Paper II. Kine Ødegård Hanssen, Sverre Grødem, Marianne Fyhn, Torkel Hafting, Gaute T. Einevoll, Torbjørn Vefferstad Ness, Geir Halnes. Responses in Fast-spiking Interneuron Firing Rates to Parameter Variations Associated with Degradation of Perineuronal Nets. Journal of Computational Neuroscience (2023) 51:283–298. DOI: 10.1007/s10827-023-00849-9. The article is included in the thesis. Also available at: https://doi.org/10.1007/s10827-023-00849-9 |
Paper III. Grødem, S., Nymoen, I., Vatne, G.H. et al. An updated suite of viral vectors for in vivo calcium imaging using intracerebral and retro-orbital injections in male mice. Nat Commun 14, 608 (2023). DOI: 10.1038/s41467-023-36324-3. The article is included in the thesis. Also available at: https://doi.org/10.1038/s41467-023-36324-3 |