Potential Sources of Intrinsic Optical Signals Imaged in Live Brain Slices

Abstract

Changes in how light is absorbed or scattered in biological tissue are termed intrinsic optical signals (IOSs). Imaging IOSs in the submerged brain slice preparation provides insight into brain activity if it involves significant water movement between intracellular and extracellular compartments. This includes responses to osmotic imbalance, excitotoxic glutamate agonists, and oxygen/glucose deprivation, the latter leading to spreading depression. There are several misconceptions regarding these signals. (1) IOSs are not generated by glial swelling alone. Although neuronal and glia sources cannot yet be directly imaged, several lines of evidence indicate that neurons contribute significantly to the changes in light transmittance. (2) Excitotoxic swelling and osmotic swelling are physiologically different, as are their associated IOSs. Hyposmotic swelling involves no detectable neuronal depolarization of cortical pyramidal neurons, only the passive drawing in of water from a dilute medium across the cell membrane. In contrast excitotoxic swelling involves sustained membrane depolarization associated with inordinate amounts of Na+ and Cl- entry followed by water. IOSs demonstrate substantial damage in the latter case. (3) Osmotic perturbations do not induce volume regulatory mechanisms as measured by IOSs. The osmotic responses measured by IOSs in brain slices are passive, without the compensatory mechanisms that are assumed to be active on a scale suggested by studies of cult…