Switching on brain transporters to switch off brain seizures

Project members:

• Associate Professor Andrew Moorhouse
  Associate Professor
  T:  +61 2 9385 2575
  E:  a.moorhouse@unsw.edu.au

• Adjunct Professor Matthias Klugmann
  Adjunct Professor
  T:  +61 2 9385 1056
  E:  m.klugmann@unsw.edu.au

• Dr John Power
  Senior Lecturer
  T:  +61-2-9065 1809
  E:  john.power@unsw.edu.au

Project main description:

Brain function is a delicate balance of neuronal excitation and inhibition. The schematic diagram above illustrates inhbitory neuronal responses mediated via the neurotransmitter GABA, and how these are affected by the neuronal Cl- transporters KCC2 and NKCC1. In neonatal neurons (left, A), KCC2 is absent and NKCC1 mediated Cl- influx results in GABA mediated depolarization and excitation. In most adult neurons (middle, B), KCC2-mediated Cl- efflux dominates Cl- homeostasis resulting in GABA mediated hyperpolarization and inhibition (A&B adapted from Ben-Ari, 2002). (C, right) KCC2 is downregulated after adult brain injury resulting in a conversion of GABA response back towards the immature depolarizing phenotype. This research project proposes that loss of KCC2 is a key event in the pathogenesis of temporal loe epilepsy and the maintenance of spontaneous seizures.

Project collaborators – external:

• Professor Junichi Nabekura
  National Institute of Physiological Sciences, Okazaki, Japan

Project supporters:

• University of NSW - NHMRC Project Grant Project ID: APP1065882