Thalamocortical Innervation Pattern in Mouse Auditory and Visual Cortex: Laminar and Cell-Type Specificity.

Despite many previous studies, the functional innervation pattern of thalamic axons and their target specificity remains to be investigated thoroughly. Here, in primary auditory cortical slices, we examined thalamic innervation patterns for excitatory and different types of inhibitory neurons across laminae, by optogenetically stimulating axons from the medial geniculate body. We found that excitatory cells and parvalbumin (PV)-expressing inhibitory neurons across layer 2/3 (L2/3) to L6 are directly innervated by thalamic projections, with the strongest innervation occurring in L4. The innervation of PV neurons is stronger than that of excitatory neurons in the same layer, with a relatively constant ratio between their innervation strengths across layers. For somatostatin and vasoactive intestinal peptide inhibitory neurons, essentially only L4 neurons were innervated by thalamic axons and the innervation was much weaker compared with excitatory and PV cells. In addition, more than half of inhibitory neurons in L1 were innervated, relatively strongly, by thalamic axons. Similar innervation patterns were also observed in the primary visual cortex. Thus, thalamic information can be processed independently and differentially by different cortical layers, in addition to the generally thought hierarchical processing starting from L4. This parallel processing is likely shaped by feedforward inhibition from PV neurons in each individual lamina, and may extend the computation power of sensory cortices.

A feedforward inhibitory circuit mediates lateral refinement of sensory representation in upper layer 2/3 of mouse primary auditory cortex.

Sensory information undergoes ordered and coordinated processing across cortical layers. Whereas cortical layer (L) 4 faithfully acquires thalamic information, the superficial layers appear well staged for more refined processing of L4-relayed signals to generate corticocortical outputs. However, the specific role of superficial layer processing and how it is specified by local synaptic circuits remains not well understood. Here, in the mouse primary auditory cortex, we showed that upper L2/3 circuits play a crucial role in refining functional selectivity of excitatory neurons by sharpening auditory tonal receptive fields and enhancing contrast of frequency representation. This refinement is mediated by synaptic inhibition being more broadly recruited than excitation, with the inhibition predominantly originating from interneurons in the same cortical layer. By comparing the onsets of synaptic inputs as well as of spiking responses of different types of neuron, we found that the broadly tuned, fast responding inhibition observed in excitatory cells can be primarily attributed to feedforward inhibition originating from parvalbumin (PV)-positive neurons, whereas somatostatin (SOM)-positive interneurons respond much later compared with the onset of inhibitory inputs to excitatory neurons. We propose that the feedforward circuit-mediated inhibition from PV neurons, which has an analogous function to lateral inhibition, enables upper L2/3 excitatory neurons to rapidly refine auditory representation.

Cross-Modality Sharpening of Visual Cortical Processing through Layer-1-Mediated Inhibition and Disinhibition.

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/L3 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/L3 VIP-cell-mediated inhibitory and disinhibitory circuits.

Sensory Cortical Control of a Visually Induced Arrest Behavior via Corticotectal Projections.

Innate defense behaviors (IDBs) evoked by threatening sensory stimuli are essential for animal survival. Although subcortical circuits are implicated in IDBs, it remains largely unclear whether sensory cortex modulates IDBs and what the underlying neural pathways are. Here, we show that optogenetic silencing of corticotectal projections from layer 5 (L5) of the mouse primary visual cortex (V1) to the superior colliculus (SC) significantly reduces an SC-dependent innate behavior (i.e., temporary suspension of locomotion upon a sudden flash of light as short as milliseconds). Surprisingly, optogenetic activation of SC-projecting neurons in V1 or their axon terminals in SC sufficiently elicits the behavior, in contrast to other major L5 corticofugal projections. Thus, via the same corticofugal projection, visual cortex not only modulates the light-induced arrest behavior, but also can directly drive the behavior. Our results suggest that sensory cortex may play a previously unrecognized role in the top-down initiation of sensory-motor behaviors.

Auditory cortex controls sound-driven innate defense behaviour through corticofugal projections to inferior colliculus.

Defense against environmental threats is essential for animal survival. However, the neural circuits responsible for transforming unconditioned sensory stimuli and generating defensive behaviours remain largely unclear. Here, we show that corticofugal neurons in the auditory cortex (ACx) targeting the inferior colliculus (IC) mediate an innate, sound-induced flight behaviour. Optogenetic activation of these neurons, or their projection terminals in the IC, is sufficient for initiating flight responses, while the inhibition of these projections reduces sound-induced flight responses. Corticocollicular axons monosynaptically innervate neurons in the cortex of the IC (ICx), and optogenetic activation of the projections from the ICx to the dorsal periaqueductal gray is sufficient for provoking flight behaviours. Our results suggest that ACx can both amplify innate acoustic-motor responses and directly drive flight behaviours in the absence of sound input through corticocollicular projections to ICx. Such corticofugal control may be a general feature of innate defense circuits across sensory modalities.