cortex

Project number:

301

Project title:

GABAergic transmission and neuronal ion regulation by cation-chloride cotransporters: development, plasticity and pathophysiology

Project supervisor:

J. Voipio/K. Kaila

Project description:

KCC2 is the neuronal K-Cl cotransporter isoform that is responsible for generating the chloride driving force underlying conventional GABAergic hyperpolarizing inhibitory postsynaptic potentials (IPSPs). KCC2 is highly localized in spines, and hence in close proximity to the presynaptic terminals of excitatory synapses. Since KCC2 is capable of mediating large fluxes of both K and Cl, it is possible that the local potassium concentration in the extracellular microdomain surrounding glutamatergic nerve endings undergoes physiologically significant changes, thereby modulating the excitability and transmitter release properties of the excitatory terminals.
The experiments will be carried out on mossy fibre terminals in the hippocampal CA3 area as well as on Schaffer collateral terminals in CA1 in rat hippocampal slices. We will examine the above hypothesis by using whole-cell patch clamping and varying the ionic concentrations in the postsynaptic neurons to influence the net fluxes mediated by KCC2. Data will be obtained for EPSC characteristics evoked by single-pulse as well as repetitive stimulation, and in addition, miniature EPSPs will be examined under the various experimental conditions.
The data will have relevance for understanding mechanisms underlying neuronal plasticity (e.g., short-term potentiation and frequency facilitation) as well as epileptogenesis, where extracellular potassium transients are known to play a key role. In this work, the team in Berlin has wide experience in the electrophysiology of excitatory transmission, while the Helsinki team has a lot of expertise in studies on KCC2.

Possible cortex partners for rotation:

Drs. Dietmar Schmitz and Sebastian Schuchmann/Dr. Dirnagl’s group, Berlin
Ole Ottersen, Oslo