Summary Cross-modality interaction in sensory perception is advantageous for animals’ survival. How cortical sensory processing is cross-modally modulated and what are the underlying neural circuits remain poorly understood. In mouse primary visual cortex (V1), we discovered that orientation selectivity of layer (L)2/3 but not L4 excitatory neurons was sharpened in the presence of sound or optogenetic activation of projections from primary auditory cortex (A1) to V1. The effect was manifested by decreased average visual responses yet increased responses at the preferred orientation. It was more pronounced at lower visual contrast, and was diminished by suppressing L1 activity. L1 neurons were strongly innervated by A1-V1 axons and excited by sound, while visual responses of L2/3 vasoactive intestinal peptide (VIP) neurons were suppressed by sound, both preferentially at the cell's preferred orientation. These results suggest that the cross-modality modulation is achieved primarily through L1 neuron and L2/3 VIP-cell mediated inhibitory and disinhibitory circuits.

Somatostatin-expressing inhibitory (SOM) neurons in the sensory cortex consist mostly of Martinotti cells, which project ascending axons to layer 1. Due to their sparse distribution, the representational properties of these neurons remain largely unknown. By twophoton imaging guided cell-attached recordings, we characterized visual response and receptive field (RF) properties of SOM neurons and parvalbumin-expressing inhibitory (PV) neurons genetically labeled in the mouse primary visual cortex. In contrast to PV neurons, SOM neurons exhibit broader spikes, lower spontaneous firing rates, smaller On/Off subfields, and broader ranges of basic RF properties such as On/Off segregation, orientation and direction tunings. Notably, the level of orientation and direction selectivity is comparable to that of excitatory neurons, from weakly-tuned to highly selective, whereas PV neurons are in general unselective. Strikingly, the evoked spiking responses of SOM cells are ϳ3-to 5-fold weaker and 20 -25 ms delayed compared with those of PV neurons. The onset latency of the latter is consistent with that of inhibitory input to excitatory neurons. These functional differences between SOM and PV neurons exist in both layer 2/3 and 4. Our results suggest that SOM and PV neurons engage in cortical circuits in different manners: while PV neurons provide fast, strong but untuned feedforward inhibition to excitatory neurons, likely serving as a general gain control for the processing of ascending inputs, SOM neurons with their selective but delayed and weak inhibition may provide more specific gating of later arriving intracortical excitatory inputs on the distal dendrites.

Synaptic inhibition plays an important role in shaping receptive field (RF) properties in the visual cortex. However, the underlying mechanisms remain not well understood, partly because of difficulties in systematically studying functional properties of cortical inhibitory neurons in vivo. Here, we established two-photon imaging guided cell-attached recordings from genetically labeled inhibitory neurons and nearby "shadowed" excitatory neurons in the primary visual cortex of adult mice. Our results revealed that in layer 2/3, the majority of excitatory neurons exhibited both On and Off spike subfields, with their spatial arrangement varying from being completely segregated to overlapped. In contrast, most layer 4 excitatory neurons exhibited only one discernable subfield. Interestingly, no RF structure with significantly segregated On and Off subfields was observed for layer 2/3 inhibitory neurons of either the fast-spike or regular-spike type. They predominantly possessed overlapped On and Off subfields with a significantly larger size than the excitatory neurons and exhibited much weaker orientation tuning. These results from the mouse visual cortex suggest that different from the push-pull model proposed for simple cells, layer 2/3 simple-type neurons with segregated spike On and Off subfields likely receive spatially overlapped inhibitory On and Off inputs. We propose that the phase-insensitive inhibition can enhance the spatial distinctiveness of On and Off subfields through a gain control mechanism.

Neurons in thalamorecipient layers of sensory cortices integrate thalamocortical and intracortical inputs. Although their functional properties can be inherited from the convergence of thalamic inputs, the roles of intracortical circuits in thalamocortical transformation of sensory information remain unclear. Here, by reversibly silencing intracortical excitatory circuits with optogenetic activation of parvalbumin-positive inhibitory neurons in mouse primary visual cortex, we compared visually-evoked thalamocortical input with total excitation in the same layer 4 pyramidal neurons. We found that intracortical excitatory circuits preserve the orientation and direction tuning of thalamocortical excitation, with a linear amplification of thalamocortical signals by about threefold. The spatial receptive field of thalamocortical input is slightly elongated, and is expanded by intracortical excitation in an approximately proportional manner. Thus, intracortical excitatory circuits faithfully reinforce the representation of thalamocortical information, and may influence the size of the receptive field by recruiting additional inputs.

Synaptic inputs underlying spike receptive fields (RFs) are key to understanding mechanisms for neuronal processing. Here, whole-cell voltage-clamp recordings from neurons in mouse primary visual cortex revealed the spatial patterns of their excitatory and inhibitory synaptic inputs evoked by On and Off stimuli. Surprisingly, neurons with either segregated or overlapped On/Off spike subfields exhibited substantial overlaps between all the four synaptic subfields. The segregated RF structures are generated by the integration of excitation and inhibition with a stereotypic pattern: the peaks of excitatory On/Off subfields are separated and flank co-localized peaks of inhibitory On/Off subfields. The small mismatch of excitation/inhibition leads to an asymmetric inhibitory shaping of On/Off spatial tunings, resulting in a great enhancement of their distinctiveness. Thus, slightly separated On/Off excitation together with intervening inhibition can create simple-cell RF structure, and the dichotomy of RF structures may arise from a fine-tuning of the spatial arrangement of synaptic inputs.