GABAergic signalling has the unique property of postsynaptic 'ionic plasticity' which is based on short-term and long-term changes in the transmembrane gradients of Cl- and HCO3-. While short-term ionic plasticity is caused by activity-dependent, channel-mediated changes in the intracellular concentrations of these two anions, long-term ionic plasticity depends on changes in the expression patterns and kinetics of proteins involved in the regulation of intraneuronal anions. In my talk, I will discuss the roles of cation-chloride cotransporters (KCC2 and NKCC1) and of the carbonic anhydrase isoform CAVII in the development of GABAergic responses at the cellular and network level in the rat hippocampus, with comparisons to data obtained from human preterm babies and epileptic patients.

While neuronal network activity is strongly influenced by changes in the expression patterns of anion-regulatory proteins, these interactions are bidirectional. Under acute pathophysiological conditions (kindling, trauma), a fast down-regulation of KCC2 and CAVII takes place in mature neurons. These events seem to reflect a 'recapitulation' of early developmental mechanisms, which may be a prerequisite for neuronal survival and for the re-establishment of connectivity in damaged brain tissue.