PT Unknown
AU Gerth, M
TI When interneurons get excited: how changes in chloride concentrations of parvalbuminergic interneurons can influence brain work and excitability
PY 2018
DI 10.22032/dbt.38235
WP https://www.db-thueringen.de/receive/dbt_mods_00038235
LA en
DE Nervenzelle; Chloridion
AB Ion homeostasis is essential for proper neuronal function, since changes in intra- or extracellular ion concentrations can cause neuropathological conditions including seizures and neuropathic pain. The Cl gradient determines the strength and polarity of GABAergic neurotransmission. It is established by the activity of cation-chloride cotransporters (CCCs), the K+-Cl co-transporter 2 (KCC2) and the Na+-K -2Cl co- transporter 1 (NKCC1). To investigate how changes in Cl concentration in inhibitory neurons affect GABAergic neurotransmission and overall excitability, KCC2 expression was inhibited in parvalbuminergic (PV+) interneurons of C57BL/6 mice. KO mice showed an ataxic gait, spontaneous epileptic seizures and a shortened life span. Immunohistochemistry revealed a loss of PV+ neurons in the hippocampus and the layer V/VI of the somatosensory cortex without detectable morphological changes. Field potential recordings showed altered short and long-term plasticity and a switch from increased inhibition at 8 weeks to enhanced excitation at 21 weeks. In vivo studies suggested increased anxiety and a significant delay of PTZ induced seizures in KO mice. This study suggests a role of KCC2 for proper Cl homeostasis in PV+ interneurons and impressively showed how impairment in GABAergic inhibition contributes to balanced brain activity. Furthermore, our results demonstrate a role of PV+ interneurons for the stress axis, neuronal excitability and higher brain functions like learning and memory.
PI Jena
ER