Maria Lindskog, Ph.D.
We study modulation of synaptic transmission and plasticity to understand the mechanisms of behavior and emotions. In particular, depression has been linked to dysfunctional glutamatergic neuronal networks and therapeutic effect of antidepressant drugs has been associated with increased synaptic remodeling. Using animal models of depression we perform electrophysiological recordings in brain slices as well as biochemical analysis and behavior.
We have shown an increased spontaneous glutamatergic transmission in the CA1 area of the hippocampus, with implications for synaptic plasticity and memory in a genetic rat model of depression, the Flinder Sensitive Line (FSL). The physiological deficits in the FSL rat can directly be explained by a decrease of astrocytic function; FSL rats show decreased levels of the glial excitatory amino acid transporter 1 (EAAT1) and greater prevalence of reactive astrocytes compared to Sprague-Dawley rats. Some, but not all, of these mechanisms are reverted by unconventional antidepressant treatments, i.e. voluntary running and a histamine H3 receptor antagonist.
Current questions in the lab are:
1) What is the interplay between glutamatergic synaptic function and astrocyte regulation?
2) Is the glutamate deficiency in depression specific for the hippocampus or general for glutamate transmission in the CNS?
3) How do the synaptic mechanisms respond to antidepressant treatments?
4) Can any of these mechanisms be used as biomarkers in affective disorders?
- Teresa Femenía Cantó, postdoc
- Salvatore Magara, PhD student
- Yvonne Johansson, PhD student
- Caitlin DuPont, undergraduate student
Hippocampal and prefrontal dopamine D1/5 receptor involvement in the memory-enhancing effect of reboxetine.
Int. J. Neuropsychopharm. (2013) May 14:1-11. [Epub ahead of print]
Dysfunctional astrocytic regulation of glutamate transmission in a rat model of depression.
Molecular Psychiatry, Epub ahead of print, February 28, 2012
Dysfunctional hippocampal activity affects emotion and cognition in mood disorders (Review)
Brain Research, Epub ahead of print, April 5, 2012
Dopamine in the hippocampus is cleared by the norepinephrine transporter.
The International Journal of Neuropsychopharmacology 15: 531-540, 2011
Postsynaptic GluA1 enables acute retrograde enhancement of presynaptic function to coordinate adaptation to synaptic inactivity.
Proceedings of the National Academy of Sciences USA 107: 21806-21811, 2010