As in our previous application, the general aim of this proposal is to study the physiological basis of magnetoencephalograms (MEGs) in order to help interpret non-invasively obtained human MEGs. Continuing and extending our previous work, we propose (1) to elucidate the nature of the currents that may give rise to the MEG, (2) to characterize the relationship between the MEG and its underlying currents in different structures of a mammalian brain and (3) to characterize the magnetic field associated with spreading depression (SD) and anoxia. Specifically, we will determine the relative contributions intraneuronal, extracellular and glial currents to the MEG in the isolated turtle cerebellum by, first of all, constructing a mathematical model that incorporates various ionic conductances in a model neuron, K+-mediated currents in the ependymal glia and ionic currents in the extracellular space and them comparing its predictions to the MEGs data to be obtained in a series of experiments in which Na-, K- and Ca-conductances and (K+) are manipulated. We will also evaluate the relative the contributions to the MEG Na- and Ca- conductances in the neuronal soma and dendrites of isolated turtle cerebellum and guinea-pig cerebellar slice by manipulating ionic composition of the bathing medium and blocking one type of conductance and then measuring the MEG due to these conductances separately. Issue two will be addressed by comparing the MEG-current relationships in the slice preparations of the primary sensorimotor cortex and its thalamocortical radiation fibers, hippocampus, cerebellum and thalamus of the guinea pig. Slice preparations are chosen, for they enable us to orient the principal core conductors horizontally in the bathing medium medium just below the detector in order to maximize the MEG as to these conductors. Regarding SD and anoxia, our work indicates that a strong magnetic field is produced during the initial stage of SD in turtle cerebellum unlike the extracellular potential which often outlasts the MEG. We will test whether this difference temporal waveform is due to a strong transcortical current in the initiation stage of and whether such a strong current is produced during the anoxic depolarization as suggested by various lines of indirect evidence. Also the origin of dc potential during and anoxia will be studied by evaluating roles of the spatial buffer mechanism and Nernst potential in producing such a potential. Furthermore, the MEG associated with the transversal current at the propagating wavefront of SD will be measured. These results taken together will be used to interpret the MEG to be measured from intact during SD and anoxia.
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