cortex

Project number:

602

Project title:

Measurements of the diffusion parameters of the CNS during pathological states using diffusion-weighted MRI and the real-time iontophoretic method employing ion-selective microelectrodes

Project supervisor:

Eva Sykova

Project description:

Although synaptic transmission is an important means of communication between neurons, neurons also communicate among themselves and with glia by extrasynaptic “volume” transmission, mediated by diffusion in the extracellular space (ECS) of the central nervous system. Diffusion in the CNS is inhomogeneous and often anisotropic. Changes in ECS volume and geometry accompany physiological neuronal activity, development, lactation, stimulation and aging, as well as numerous pathological states, e.g., anoxia/ischemia, seizures, injury, gliosis, demyelination, inflammation, Parkinson’s and Alzheimer’s diseases and in tumors. Ionic changes and amino acid release result in cellular swelling, compensated for by ECS shrinkage and a decrease in the apparent diffusion coefficients of neuroactive substances or water (ADCW) as determined by diffusion analysis using the real-time iontophoretic method employing ion-selective microelectrodes or diffusion-weighted MRI. Recent studies indicate that diffusion in the ECS is affected by ECS volume inhomogeneities, which are the result of a more compacted space in certain regions, e.g., in the vicinity of oligodendrocytes. The extracellular matrix also changes ECS geometry and forms diffusion barriers, which may result in diffusion anisotropy. Diffusion therefore plays an important role in extrasynaptic transmission, for example in functions involving long-range information processing such as vigilance, sleep, depression, chronic pain, LTP, LTD, memory formation and other plastic changes in the CNS. Plastic changes in ECS volume, tortuosity and anisotropy significantly affect neuron-glia communication, the spatial relation of glial processes towards synapses, glutamate or GABA ‘spillover’, synaptic cross-talk, ionic homeostasis and the movement and/or accumulation of neuroactive substances in the brain. The changes that occur during pathological states can be important for diagnosis, drug delivery and treatment.

Possible cortex partners for rotation:

Partner 2, Bochum: human cortical plasticity, electrophysiology

Partner 3, Helsinki: neuronal communication, plasticity, electrophysiology (including ion-selective microelectrodes)