Our research focuses on GABAergic transmission in the mammalian brain. Fast synaptic inhibition is crucial for the timing of action potential firing, thus shaping network activity and behaviour. The aspect of timing has been intensely investigated in the cerebellum. The activity of Purkinje cells (the only out put of the cerebellar cortex) can be precisely timed in response to sensory stimulation. This precision is partly achieved via feed forward inhibition from molecular layer interneurons. By selectively modulating the interneuron to Purkinje cell synapse we can control this feed forward inhibition to investigate its role in shaping Purkinje cell activity patterns and cerebellum-dependent behaviour.

In the hippocampus timing is thoroughly investigated in the context of network oscillations, which are thought to serve as a clock signal for the encoding of information. We are manipulating the input or output stages of GABAergic interneurons to test their role in network activity and behaviour.

Wulff, P., Schonewille, M., Renzi, M., Viltono, L., Sassoe-Pognetto, M., Bardura, A., Gao, Z., Hoebeek, F.E., van Dorp, S., Wisden, W., Farrant, M., De Zeeuw, C.I. (2009) Synaptic inhibition of Purkinje cells mediates consolidation of vestibulo-cerebellar motor learning. Nat Neurosci 12, 1042-1049.

Wulff, P., Ponomarenko, A.A., Bartos, M., Korotkova, T.M., Fuchs E.C., Baehner, F., Both, M., Tort, A.B.L., Kopell, N.J., Wisden, W. and Monyer, H. (2009) Hippocampal theta rhythm and its coupling with gamma oscillations require fast inhibition onto parvalbumin-positive interneurons. PNAS 106, 3561-3566.

Goetz, T., Arslan, A., Wisden, W., and Wulff, P. (2007). GABA_A receptors: structure and function in the basal ganglia. Prog Brain Res 160, 21-41.

Wulff, P., Goetz, T., Leppä, E., Linden, A.M., Renzi, M., Swinny, J.D., Vekovischeva, O.Y., Sieghart, W., Somogyi, P., Korpi, E.R., Farrant, M., and Wisden, W. (2007). From synapse to behaviour: rapid modulation of defined neuronal types with engineered GABA_A receptors. Nat Neurosci 10, 923-929.

Wulff, P., and Wisden, W. (2005). Dissecting neural circuitry by combining genetics and pharmacology. Trends Neurosci 28, 44-50.

Molecular Biology, Mouse Transgenesis, Viral Gene Delivery