title: Optical current source density analysis in hippocampal organotypic culture shows that spreading depression occurs with uniquely reversing currents.
abstract: Spreading depression (SD) involves current flow through principal neurons, but the pattern of current flow over the expanse of susceptible tissues or individual principal neurons remains undefined. Accordingly, tissue and single cell maps made from digital imaging of voltage-sensitive dye changes in hippocampal organotypic cultures undergoing SD were processed via optical current source density analysis to reveal the currents associated with pyramidal neurons. Two distinctive current flow patterns were seen. The first was a trilaminar pattern (420 microm2) that developed with the onset of SD in CA3 pyramidal neurons, in which SD most often began. This initial pattern comprised a somatic current sink with current sources to either side in the dendrites that lasted for seconds extending into the first aspect of the classical "inverted saddle" interstitial direct current waveform of SD. Next, the somatic sink backpropagated at a speed of millimeters per minute into the proximal dendrites, resulting in a reversal of the initial current flow pattern to its second orientation, namely dendritic sinks associated with a somatic source. The latter persisted for the remainder of SD in CA3 and was the only pattern seen in CA1, in which SD was rarely initiated. This backpropagating SD current flow resembles that of activity-dependent synaptic activation. Retrograde and associative signaling via principal neuron current flow is a key means to affect tissue function, including synaptic activation and, by extension, perhaps SD. Such current-related postsynaptic signaling might not only help explain SD but also neuroprotection and migraine, two phenomena increasingly recognized as being related to SD.
authors.affiliation: Department of Neurology, The University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Phillip E
authors.initials: PE
authors.lastname: Kunkler
authors.forename: Raymond E
authors.initials: RE
authors.lastname: Hulse
authors.forename: Michael W
authors.initials: MW
authors.lastname: Schmitt
authors.forename: Charles
authors.initials: C
authors.lastname: Nicholson
authors.forename: Richard P
authors.initials: RP
authors.lastname: Kraig
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D013181:Cortical Spreading Depression / Q000502:physiology*; D003952:Diagnostic Imaging / Q000379:methods; D004558:Electric Stimulation / Q000379:methods; D006624:Hippocampus / Q000166:cytology*; D007150:Immunohistochemistry / Q000379:methods; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D008959:Models, Neurological; D016900:Neurofilament Proteins / Q000378:metabolism; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques / Q000379:methods; D017966:Pyramidal Cells / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric; D013343:Styrenes / Q000378:metabolism; D013997:Time Factors
chemical_list: D016900:Neurofilament Proteins; C096453:RH 795; D013343:Styrenes; C013411:biocytin; D008239:Lysine