Changes in Dendritic Axial Resistance Alter Synaptic Integration in Cerebellar Purkinje Cells

The ability of neurons to process synaptic inputs depends critically on their passive electrical properties. The intracellular resistivity, R(i), is one of the parameters that determine passive properties, yet few experiments have explored how changes in R(i) might affect synaptic integration. In this work, I addressed this issue by using targeted dendritic occlusion to locally increase R(i) in cerebellar Purkinje cells and examining the consequences of this manipulation for the summation of synaptic inputs. To achieve dendritic occlusion, I used two glass micropipettes to gently pinch the dendritic trunk close to the soma. This pinching produced stereotypical changes in the responses to test pulses applied at the soma under voltage and current clamp. A simple model confirmed that these changes were due to increases in R(i) in the dendritic trunk. These localized increases in R(i) produced striking alterations in the shapes of postsynaptic potentials at the soma, increasing their amplitude and accelerating their decay kinetics. As a consequence, dendritic occlusion sharpened temporal precision during the summation of synaptic inputs. These findings highlight the importance of local changes in intracellular resistivity for the passive electrical properties of neurons, with implications for their ability to process synaptic information.This work was begun in the laboratory of Michael Ha¨usser (University College London) with the support of a short-term travel grant from the Wellcome Trust. Subsequent funding was provided by the John Curtin School of Medical Research