Whole-Cell Recording of Neuronal Membrane Potential during Behavior

Neuronal membrane potential is of fundamental importance for the mechanistic understanding of brain function. This review discusses progress in whole-cell patch-clamp recordings for low-noise measurement of neuronal membrane potential in awake behaving animals. Whole-cell recordings can be combined with two-photon microscopy to target fluorescently labeled neurons, revealing cell-type-specific membrane potential dynamics of retrogradely or genetically labeled neurons. Dual whole-cell recordings reveal behavioral modulation of membrane potential synchrony and properties of synaptic transmission in vivo. Optogenetic manipulations are also readily integrated with whole-cell recordings, providing detailed information about the effect of specific perturbations on the membrane potential of diverse types of neurons. Exciting developments for future behavioral experiments include dendritic whole-cell recordings and imaging, and use of the whole-cell recording pipette for single-cell delivery of drugs and DNA, as well as RNA expression profiling. Whole-cell recordings therefore offer unique opportunities for investigating the neuronal circuits and synaptic mechanisms driving membrane potential dynamics during behavior.