Imperfect Space Clamp Permits Electrotonic Interactions between Inhibitory and Excitatory Synaptic Conductances, Distorting Voltage Clamp Recordings
Figure 6
Examples of voltage clamp errors in different dendritic arborizations.
Neuronal morphology influences voltage clamp accuracy. All simulations presented in this figure were performed on 300 excitatory and 300 inhibitory synapses which were first activated individually, and thereafter the arithmetic sum of individual IV relationships (at holding potentials between −100 mV to 0 mV in jumps of 10 mV) was compared to the combined E/I activation. Examples of somatic currents were recorded at 0 and −60 mV in control (black) and after blockage of inhibitory inputs (red) conditions. A and B, Analysis of the expected voltage clamp error for synaptic activation in different parts of a cortical layer 5 cell. A, Voltage clamp is very inaccurate when synaptic input is restricted to the apical dendrites, which are distanced from the clamped soma. Note the substantial underestimation by the RPC of the excitatory current when inhibitory inputs are active (up) and the large discrepancies between the combined E/I IV relationships (bottom, black) to the expected IV relationship of the individual conductances (bottom, green). B, In the basal tree, the voltage clamp is reliable, due to large dendritic diameters, proximity to the soma and few bifurcations of these dendrites (right). Middle – schematic image of the cell. C, ON-OFF direction selective ganglion neurons are much smaller than cortical pyramidal neurons, but have dendritic trees with small branch diameters and extensive bifurcations that contribute to voltage clamp errors. Synapses were randomly distributed either at the OFF (up) or ON (bottom) dendritic layers. Dendrites connecting the OFF layer to the soma are marked in red. Voltage clamp errors are larger for the OFF layer dendrites, especially when the connecting dendrites are thin (1 µm, bold), and became similar to the ON layer for wider dendrites (2 µm, dotted).