Attentional modulation is orthogonal to disinhibition by VIP interneurons in primary visual cortex

Attentional modulation of sensory processing is a key feature of cognition, yet its neural circuit basis is poorly understood. A candidate mechanism is the disinhibition of pyramidal cells through vasoactive intestinal peptide (VIP) and somatostatin (SOM) positive interneurons. However, the interaction of attentional modulation and VIP-SOM disinhibition has never been directly tested. We used all-optical methods to bi-directionally manipulate VIP interneuron activity as mice performed an attention switching task. We measured the activity of VIP, SOM and parvalbumin (PV) positive interneurons and pyramidal neurons identified in the same tissue and found that although activity in all cell classes was modulated by both attention and VIP manipulation, their effects were orthogonal. Attention and VIP-SOM disinhibition relied on distinct patterns of changes in activity and reorganisation of interactions between inhibitory and excitatory cells. These results reveal the remarkable ability of cortical circuits to multiplex strong yet non-interacting modulations in the same neural population.