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.