Microfabricated solid-state ion-selective electrode probe for measuring potassium in the living rodent brain: Compatibility with DC-EEG recordings to study spreading depression

There is considerable need in neuroscience research to reliably measure concentrations of extracellular ions in the living brain as the dynamics of ion levels increasingly is considered to play a key role in the pathophysiology of many brain disorders. Unfortunately, most probes currently used for direct measurement of extracellular ion concentrations in living brain tissue in experimental animals have considerable limitations. They are custom-made glass capillary ion-selective microelectrodes that are fragile, timeconsuming to prepare, and can practically only be used to measure at one depth and one location in the brain. We here present the design and fabrication of a novel type of miniaturized probe that can simultaneously measure, in the brain of a living animal, multiple parameters relevant to the neurological phenomenon of spreading depression (SD) at multiple depths and locations. SD is characterized by a slowly propagating wave of initial neuronal and glial cell depolarization that is followed by depression of activity. SD is accompanied by a massive redistribution of ions, including K+, between intracellular and extracellular compartments and is considered important in brain diseases such as stroke, traumatic brain injury, and migraine with aura. This work focuses on the functionalization of fabricated probes for measuring changes in extracellular K+ concentration (and its associated changes in neuronal activity) using an ion-selective potentiometric sensor. We show that the choice of conductive polymer and the method of electro-deposition is critical to obtain low cross-sensitivity for pH and O-2. The sensor's response to IC is approximately linear between 2 and 40 mM with a voltage-response of 39 mV/log[K+]. Proof-of-principle in vivo brain recordings were performed in the cortex of a wild-type mouse during induction of cortical SD. We reliably measured the theoretically expected rise and fall of brain tissue K+ levels during a locally induced cortical SD. We envisage that our probe can be of great use to reliably measure K+, without being affected by pH or O-2 changes, in the living brain and be widely applicable in neuroscience research. (C) 2014 Elsevier B.V All rights reserved