Maria Lindskog
Collaboration of plasticity mechanisms
A healthy brain is a brain in balance, but being in balance is far from being static. We are interested in understanding the synaptic tuning mechanisms that generate the robust—yet highly plastic—system that is the brain. Rather than serving as a volume control in which neurotransmission can be turned up or down, we compare synaptic tuning to a gearbox, in which the overall drive and acceleration are modulated thorough different forms of plasticity. Our preferred model system is the rat or mice hippocampal slice where we do field and patch-clamp recordings to directly assess synaptic activity. The functional synaptic results are combined with immunohistochemistry, western-blot analysis and animal behavior.
Astrocytes are fundamental regulators of excitatory synaptic transmission, but much less is known about astrocytes compared to neurons. The very close synapse/astrocyte interaction makes this relationship challenging, and intriguing, to study. We have added direct recordings from astrocytes to our methodological tool-box to be able to tease out the different mechanisms.
Our interest in astrocytes was spurred by the fact that astrocytes are frequently affected in psychiatric disorders. There is emerging results showing that many mental disorders are associated with defects in synaptic connectivity, and we think that this may be due to defective regulation by astrocytes, rather than a synaptic problem per se. We are using animal models for depression and Alzheimer’s disease to translate our findings on synaptic tuning to these diseases, with the aim to identify new targets to develop disease-modifying therapies.
Publications
Part of Journal of Alzheimer's Disease, p. 1017-1037, 2024
- DOI for Early Astrocytic Dysfunction Is Associated with Mistuned Synapses as well as Anxiety and Depressive-Like Behavior in the AppNL-F Mouse Model of Alzheimer's Disease
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The effect of ketamine on synaptic mistuning induced by impaired glutamate reuptake
Part of Neuropsychopharmacology, p. 1859-1868, 2023
- DOI for The effect of ketamine on synaptic mistuning induced by impaired glutamate reuptake
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Astrocytic uptake of neuronal corpses promotes cell-to-cell spreading of tau pathology
Part of Acta neuropathologica communications, 2023
- DOI for Astrocytic uptake of neuronal corpses promotes cell-to-cell spreading of tau pathology
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Part of Journal of Neuroinflammation, 2023
- DOI for Amyloid-beta accumulation in human astrocytes induces mitochondrial disruption and changed energy metabolism
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Part of Journal of Neuroinflammation, 2023
- DOI for Intracellular deposits of amyloid-beta influence the ability of human iPSC-derived astrocytes to support neuronal function
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Part of Journal of Alzheimer's Disease, p. 565-583, 2022
- DOI for Mitochondrial Alterations in Neurons Derived from the Murine AppNL-F Knock-In Model of Alzheimer's Disease
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Part of International Journal of Molecular Sciences, 2021
- DOI for The Role of Central Serotonin Neurons and 5-HT Heteroreceptor Complexes in the Pathophysiology of Depression: A Historical Perspective and Future Prospects
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