Claudio Rivera group

Research People Selected publications

Interplay between neurotrophic factors and chloride homeostasis


Claudio Rivera
Research Director
P.O. Box 56, FI-00014 University of Helsinki
Phone: 57645 (internal), +358 50 3684 369
Email: claudio.rivera at

Chloride homeostasis is an important mechanism involved in a variety of cellular events such as volume regulation, proliferation and migration. In neurons the setting of intracellular chloride concentration is in addition crucial for the changes GABAA mediated transmission that take place during development and trauma. These changes are regulated by the functional expression of the chloride transporters KCC2 and NKCC1. Our group has been particularly interested in the interplay between neurotrophic factors and chloride homeostasis. Because neurotrophic factors are regulated by neuronal activity and can regulate inhibitory synapses, they are key molecules to mediate developmental and adult forms of synaptic plasticity during physiological and pathophysiological conditions. In this regard our group has been successful as we have elucidated part of the mechanisms involved in the interplay between intracellular chloride regulation and neurotrophic factors in developing neurons as well as in clinically important paradigms for epilepsy and CNS injury. Neurodegeneration is a devastating sequel common to many neuropathological conditions. A current view is that the brain reacts to pathological insults by activating developmental like programs for survival, regeneration and replacement of damaged neurons.  For instance, after injury mature central neurons become dependent on BDNF trophic support for survival. The reasons for this dependency are poorly studied.  In resent works we descried a novel mechanism explaining the neuroprotective action of BDNF after trauma: a) we found that the post-traumatic effect of GABAA receptors is set by the down-regulation of the K-Cl cotransporter KCC2 and functional presence of Na-K-Cl cotransporter NKCC1; b) post-traumatic GABA depolarization induces p75NTR up-regulation that promotes death signalling; c) BDNF trophic support counterbalance this death signalling and thus exerts a neuroprotective action. However the intrinsic mechanism causing trauma induced decrease of KCC2, BDNF requirement for neuronal survival and consequent rearrangement of post-traumatic network are not known.  We are currently testing how global this mechanism is in different in vivo trauma models. Our current strategy is to develop tools to investigate in more detail this mechanism with the aim to find novel and refined therapeutically approaches to tackle neurodegeneration.

The major function of K-Cl cotranporter KCC2 is to extrude chloride. Resent results have shown that the developmental up-regulation of KCC2 is important for the formation of dendritic spines and formation of glutamatergic synapses. Intriguingly this is not mediated by its chloride extrusion activity but through the interaction of KCC2 with intracellular proteins.  We have now found a number of new intracellular proteins that mediates the regulatory action of KCC2 on the actin cytoskeleton. Our future aim is the implement these tools to investigate the structural role of KCC2 in dendritic spine plasticity and the interplay between inhibitory and excitatory transmission during development and trauma.

Our final aim is to define the role of the interplay between the proteins regulating chloride homeostasis and neurotrophic factors in neuronal wiring and rewiring in the developing and post-traumatic brain.