COVID-19 pandemic continues worldwide with many variants arising, especially those of variants of concern (VOCs). A recent VOC, Omicron (B.1.1.529), which obtains a large number of mutations in the receptor-binding domain (RBD) of the spike protein, has risen to intense scientific and public attention. Here we studied the binding properties between the human receptor ACE2 (hACE2) and the VOC RBDs and resolved the crystal and cryo- EM structures of the Omicron RBD-hACE2 complex, as well as the crystal structure of Delta RBD-hACE2 complex. We found that, unlike Alpha, Beta and Gamma, Omicron RBD binds to hACE2 at a similar affinity compared to that of the prototype RBD, which might be due to compensation of multiple mutations for both immune escape and transmissibility. The complex structures of Omicron-hACE2 and Delta-hACE2 reveal the structural basis of how RBD-specific mutations bind to hACE2.

SUMMARY Responses of neurons in early visual cortex change little with training, and appear insufficient to account for perceptual learning. Behavioral performance, however, relies on population activity, and the accuracy of a population code is constrained by correlated noise among neurons. We tested whether training changes interneuronal correlations in the dorsal medial superior temporal area, which is involved in multisensory heading perception. Pairs of single units were recorded simultaneously in two groups of subjects: animals trained extensively in a heading discrimination task, and “naïve” animals that performed a passive fixation task. Correlated noise was significantly weaker in trained versus naïve animals, which might be expected to improve coding efficiency. However, we show that the observed uniform reduction in noise correlations leads to little change in population coding efficiency when all neurons are decoded. Thus, global changes in correlated noise among sensory neurons may be insufficient to account for perceptual learning.

Summary Single sensory neurons can be surprisingly predictive of behavior in discrimination tasks. We propose this is possible because sensory information extracted from neural populations is severely restricted, either by near-optimal decoding of a population with information-limiting correlations or suboptimal decoding that is blind to correlations. These have different consequences for choice correlations, the correlations between neural responses and behavioral choices. In the vestibular and cerebellar nuclei and the dorsal medial superior temporal area, we found that choice correlations during heading discrimination are consistent with near-optimal decoding of neuronal responses corrupted by information-limiting correlations. In the ventral intraparietal area, the choice correlations are also consistent with the presence of information-limiting correlations, but this area does not appear to influence behavior although the choice correlations are particularly large. These findings demonstrate how choice correlations can be used to assess the efficiency of the downstream read-out and detect the presence of information-limiting correlations.

Functional links between neuronal activity and perception are studied by examining trial-by-trial correlations (choice probabilities) between neural responses and perceptual decisions. We addressed fundamental issues regarding the nature and origin of choice probabilities by recording from subcortical (brainstem and cerebellar) neurons in rhesus monkeys during a vestibular heading discrimination task. Subcortical neurons showed robust choice probabilities that exceeded those seen in cortex (area MSTd) under identical conditions. The greater choice probabilities of subcortical neurons could be predicted by a stronger dependence of correlated noise on tuning similarity, as revealed by population decoding. Significant choice probabilities were observed almost exclusively for neurons that responded selectively to translation, whereas neurons that represent net gravito-inertial acceleration did not show choice probabilities. These findings suggest that the emergence of choice probabilities in the vestibular system depends on a critical signal transformation that occurs in subcortical pathways to distinguish translation from orientation relative to gravity.