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Brannon, Terrence LINEAR VS.NONLINEAR SYNAPTIC INTEGRATION IN A MODEL CA1 PYRAMIDAL CELL Intracellular recordings indicate that dendrites of CA1 pyramidal cells contain voltage-dependent inward currents, including NMDA, Na+, and Ca++ currents, which can amplify synaptic inputs and support the initiation and propagation of dendritic action potentials. Though dendritic spike-generating mechanisms would seem likely to produce strong superlinear interactions among nearby excitatory synapses, a recent study using dual glutamate pipettes (Cash & Yuste, Neuron, 1999, 22:383) found that dendritic integration in response to activation of both pipettes was usually linear or sublinear (compared to prediction based on individual pipette responses), depending on which combination of dendritic compartments was activated. Similar results were obtained for synaptic stimulation using extracellular electrodes (see also Urban & Barrionuevo, PNAS, 1998, 95:11450). To determine whether superlinear synaptic interactions could have been overlooked in these studies, we used detailed compartmental simulations of a CA1 cell to quantify interactions between two synaptic stimuli within the stratum radiatum, with precise control of both their intensity and relative position. Consistent with experiments, we found numerous stimulus configurations that produced linear or sublinear integration as measured at the soma. However, superlinear integration within oblique dendrites could be missed whenever the two stimuli were individually sufficient to fire the dendritic branch(es) involved---as is likely the case for the bulk stimulation methods used experimentally. Based on these results, we infer that CA1 cells could support expansive boosting of synaptic inputs confined to their oblique or other thin dendrites, whose outputs are then integrated through a compressive nonlinearity in the main apical trunk and/or cell body. Supported by NSF.
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