Differential Tuning of Excitation and Inhibition Underlies Direction Selectivity in Ferret Visual Cortex

A hallmark of sensory cortical circuit function is the reliable expression of selective neuronal responses that enable the encoding of specific stimulus features. In principle, a variety of factors may contribute to a cortical neuron’s response selectivity including the tuning and strength of excitatory and inhibitory synaptic inputs, dendritic nonlinearities, and spike threshold. But how these factors act in combination to produce response selectivity remains poorly understood.    Here we employ a combination of techniques including in vivo whole-cell recording, synaptic and cellular resolution in vivo 2-photon calcium imaging, and GABAergic-selective optogenetic manipulation to dissect the factors contributing to direction selective responses of layer 2/3 neurons in ferret visual cortex. Two-photon calcium imaging of dendritic spines revealed that each neuron receives a mixture of excitatory synaptic inputs selective for the somatic preferred or null direction of motion. In contrast, in vivo whole-cell patch clamp recordings revealed a striking degree of direction selectivity in subthreshold membrane potential responses that was significantly correlated with the degree of direction selectivity evident in the neuron’s spiking behavior. Several lines of evidence including conductance measurements suggest that inhibition preferentially suppresses responses to the null direction of motion. Consistent with this idea, optogenetic inactivation of GABAergic neurons in layer 2/3 preferentially enhanced responses to the null direction of motion, causing a reduction in membrane potential direction selectivity. Furthermore, using a new technique to optogenetically map connectivity from inhibitory onto excitatory neurons in layer 2/3 in vivo, we find that layer 2/3 inhibitory neurons make long-range, intercolumnar projections to excitatory neurons that prefer the opposite direction of motion. We conclude that intracortical inhibition exerts a major influence on the degree of direction selectivity in layer 2/3 of ferret visual cortex by preferentially suppressing responses to the null direction of motion.