Research interests

The studies of this lab are directed at the identification of molecular mechanisms that underlie synchronous activity in the central nervous system and that are relevant for numerous cognitive processes including the building of representations, learning and memory. A number of compelling studies and computational simulations data provide evidence that networks of inhibitory neurones (GABAergic neurones) play a pivotal role in the synchronization of neuronal ensembles, thus underlying the generation and maintenance of oscillations in different frequency bands. Oscillatory activity in turn, has been proposed to be critical for a number of cognitive tasks, including object representation, learning and memory. The goal of our studies is to modify the recruitment of GABAergic interneurones in defined brain regions. We have generated mouse mutants with specific ablations of glutamate receptors or gap junction channels that are restricted to GABAergic interneurones thus affecting either the excitatory drive onto this cell population or their electrical connectivity. Our studies entail analysis from the single cell level to the network activity in vitro (acute slice preparation) and in vivo. Genetically modified mice with altered expression of critical genes in GABAergic interneurones are an important tool for subsequent electrophysiological studies to investigate neuronal activity at the single cell and network level in cortex and hippocampus in freely moving mice. These investigations are further complemented by behavioural studies. Given the large diversity of GABAergic interneurones, some of our studies aim at the identification of defined GABAergic subpopulations. To this end transgenic mice are produced in which these neuronal subpopulations are 'labelled' using the in vivo marker green fluorescent protein (GFP). The subsequent electrophysiological studies on fluorescent neurones in these mice should aid in identifying the GABAergic cell types involved in different forms of network oscillations. Finally, in transgenic mice that express GFP in subsets of GABAergic interneurones, we have found that unlike the vast majority of GABAergic interneurones that are generated embryonically, certain GABAergic interneurones continue to be generated after birth and even in the adult. Postnatal neurogenesis of GABAergic interneurones that migrate into the cortex, striatum and hippocampus is a novel form of plasticity that has become another major focus of our research.

 

Methods applied

Mouse genetics Patch-clamp recordings in acute hippocampal and cortical slices Behavioural studies to investigate working and long-term memory Calcium imaging In vivo electrophysiological recordings (using tetrodes and silicone probes) in freely moving mice