We propose to study the physiological basis of MEG and EEG in a slice preparation of the pig primary somatosensory cortex (SI). Earlier we studied the same issue in isolated turtle cerebellum in vitro and guinea pig hippocampal slices. In the previous cycle, we showed for the first time that three distinct types of signals - intra- and extracellular field potentials and magnetic field - can be quantitatively explained with our mathematical network model based on RD Traub's and thus provided a fundamental understanding of origin of MEG in hippocampus. Based on these results we are now ready to tackle the same issue in the most difficult, but most important structure for MEG and EEG, i.e. the cerebral cortex. In a related project, we have studied the somatic evoked potentials (SEPs) and magnetic fields (SEFs) produced by the porcine SI cortex. This research has led to new insights into the genesis of MEG and EEG signals in the SI cortex in vivo. We propose to extend our in vitro work to the porcine SI cortex to study the origin of these signals in more detail. Specifically, we will address four aims. (1) Determine whether there is an invariance in the maximum current that can be generated per unit cross-sectional area of the cortex. Our previous studies indicate such an invariance (approximately equals 1 nA-m/mm2) across species and brain structures. This issue is crucial since it can provide an important physiological constraint on inverse solution algorithms used to interpret human MEG and EEG. (2) Determine the basis for another invariance found across species, i.e. the invariance in direction of the current underlying the first cortical response called N20. This is always from a deep to a superficial layer in humans, monkey and pig. We will test a hypothesis resulting from our in vivo SI study, i.e. it is due to an initial nearly instantaneous spread of activation from dendrites to the soma which then produces intracellular currents directed from the soma toward distal apical dendrites and also serves as the basis for backpropagation. (3) Determine the origin of the long-term potentiation (LTP) in the SI detected outside the brain in our in vivo study. This result can open the possibility for studying LTP in humans. We plan to determine its synaptic loci in vitro in the cortex of the animal exhibiting LTP in vivo. (4) Determine effects of blocking specific active channels in cortical neurons on MEG and EEG signals. Our hippocampal slice study has shown the importance of calcium and C channel in the generation of MEG and EEG signals. We will study the role of various conductances by using selective channel blockers and measuring their effects with intracellular and extracellular potential recordings and MEG. The role of calcium-mediated current in evoked response will be determined by a combination of optical measurements of intracellular calcium concentration, intra- and extracellular potentials.
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