Spatial ionic conditions of potassium-chloride co-transporter KCC2 function in hippocampal networks (Frequency and condition dependence of KCC2 transport function)

• Applicant: Dr. Egor Byvaltcev
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 576748885

This project investigates how fluctuations in intracellular chloride ([Cl⁻]i) within dendritic spines (and shafts) and extracellular potassium ([K⁺]o) near synapses regulate the neuronal cotransporter KCC2, with a particular focus on conditions that promote its reverse transport mode. The work will address five key questions: (1) what levels of [K⁺]o and excitatory activity are sufficient to induce KCC2 reversal, (2) whether excitatory inputs generate [Cl⁻]i transients in dendritic shafts via KCC2 mediated ionic uptake and how these affect GABAergic inhibition, (3) how the frequency of inhibitory inputs can overload shafts-localised KCC2 and drive local [Cl⁻]i and [K⁺]o accumulation, (4) the extent to which dendritic [Cl⁻]i influences spine chloride homeostasis and KCC2 function, and (5) how changes in extracellular space volume, as seen during astrocytic swelling or pathological states, alter ionic dynamics and KCC2 activity. By systematically dissecting these mechanisms, the project will define the physiological and pathological conditions under which KCC2 switches modes. This knowledge will clarify how excitation and inhibition jointly control chloride and potassium homeostasis, thereby advancing our understanding of synaptic integration, network stability, and the ionic disturbances that underlie neurological disorders.

• DFG Programme: Research Grants