Thalamic activation of the visual cortex at the single-synapse level.

Deciphering thalamocortical (TC) activation at the level of individual synapses is essential to understanding how the cortex processes sensory information. In this work, we studied TC computation underlying the emergence of orientation selectivity in the mammalian primary visual cortex (V1). Using two-photon glutamate imaging and optogenetic cortical silencing in vivo, we identified and characterized TC synapses onto mouse V1 layer 4 neurons. We found that TC- but not corticocortical-recipient spines lacked postsynaptic Ca2+ signals. Our results directly validate the core predictions of Hubel and Wiesel's feedforward model and reveal distinctive synaptic properties that are critical for cortical computation and plasticity. Editor's summary: What is the synaptic basis for orientation selectivity in mouse primary visual cortex? To address this question, Chen et al. combined imaging of orientation-tuned cortical layer 4 neurons, single-cell expression of genetically encoded biosensors, single-spine calcium ion and glutamate imaging, optogenetic silencing, and single-cell–initiated rabies virus tracing. They found that layer 4 orientation-tuned neurons in primary visual cortex receive thalamic inputs from canonical, nonorientation-tuned neurons. By contrast, corticocortical synaptic inputs were mostly orientation tuned. The authors constructed functional wiring diagrams of active thalamic connections to cortical neurons tuned for specific sensory stimuli in the brain. These results provide substantial support for a model originally proposed by Hubel and Wiesel that the spatial offset of ON and OFF thalamic receptive fields underlies cortical orientation tuning. —Peter Stern [ABSTRACT FROM AUTHOR]