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Juan, C.

Publications and source records attributed to Juan, C..

4 recordsLinked to original sources

Decoding Smell from Receptor Structure

Olfaction enables animals to detect and discriminate a vast array of chemicals, yet how odorant receptors (ORs) encode ligand selectivity remains unclear. Although recent advances in protein structure prediction have expanded access to OR structures, linking these to function at scale has been challenging. Here, we combined AlphaFold3-predicted receptor structures with protein language model embeddings and in vivo pS6-IP-Seq measurements of olfactory sensory neuron activation across a chemically diverse odor panel to train a deep learning model of OR-ligand interactions. The resulting framework predicts receptor responses, organizes receptors by functional similarity independent of sequence, and identifies structural determinants of ligand selectivity. These findings establish a structure-based map of OR function and provide a foundation for predictive and interpretable models of olfactory coding.

molecular biology↗

Frequency coding of multisensory integration in the local field potentials of the medial pulvinar

The pulvinar is a posterior thalamic nucleus, with a heterogeneous anatomo-functional organization. It is divided into four parts, including the medial pulvinar, which is densely connected with primary unisensory and multisensory cortical regions, and subcortical structures, including the superior colliculus. Based on this connectivity, the medial pulvinar may play an important role in sensory processing and multisensory integration. However, its contribution to multisensory integration has rarely been directly investigated. To fill this knowledge gap, two macaque monkeys were trained on a fixation task, during which auditory, visual and audiovisual stimuli were presented. We characterize local field potentials of the medial pulvinar associated with these stimuli. In the temporal domain, we describe an early and a late period showing multisensory integration, both dominated by sub-additive processes (the audiovisual response is inferior to the sum of the unisensory responses). In the frequency domain, multisensory integration, mostly sub-additive, is predominant in the lower frequencies (90% of recorded signals in 4.5-8.5Hz and 96% in 8.5-20Hz). Prevalence largely decreases in high frequencies (54% in 35-60Hz, 37% in 60-120Hz). This suggests that the medial pulvinar is a multisensory hub, integrating visual and auditory information in different frequency bands and contributing to cortico-pulvino-cortical multisensory computational loops.

neuroscience↗

Multisensory integration in neurons of the medial pulvinar of macaque monkey

The pulvinar is a heterogeneous thalamic nucleus, which is well developed in primates. One of its subdivisions, the medial pulvinar, is connected to many cortical areas, including the visual, auditory and somatosensory cortices, as well as with multisensory areas and premotor areas. However, except for the visual modality, little is known about its sensory functions. A hypothesis is that, as a region of convergence of information from different sensory modalities, the medial pulvinar plays a role in multisensory integration. To test this hypothesis, two macaque monkeys were trained to a fixation task and the responses of single-units to visual, auditory and auditory-visual stimuli were examined. Analysis revealed auditory, visual and multisensory neurons in the medial pulvinar. It also revealed multisensory integration in this structure, mainly subadditive and suppressive. These findings show that the medial pulvinar is involved in multisensory integration.

neuroscience↗

Encoding of odors by mammalian olfactory receptors

O_LIIdentified ligands for > 500 mouse ORs C_LIO_LIORs are specifically tuned towards individual odorants and their molecular properties C_LIO_LIOdor molecular properties are informative of odor responses C_LIO_LIPredictive modeling and convergent evolution analyses suggest specific residues within a canonical location for odorant binding C_LI Olfactory receptors (ORs) constitute the largest multi-gene family in the mammalian genome, with hundreds to thousands of loci in humans and mice respectively1. The rapid expansion of this massive family of genes has been generated by numerous duplication and diversification events throughout evolutionary history. This size, similarity, and diversity has made it challenging to define the principles by which ORs encode olfactory stimuli. Here, we performed a broad surveying of OR responses, using an in vivo strategy, against a diverse panel of odorants. We then used the resulting interaction profiles to uncover relationships between OR responses, odorants, odor molecular properties, and OR sequences. Our data and analyses revealed that ORs generally exhibited sparse tuning towards odorants and their molecular properties. Odor molecular property similarity between pairs of odorants was informative of odor response similarity. Finally, ORs sharing response to an odorant possessed amino acids at poorly conserved sites that exhibited both, predictive power towards odorant selectivity and convergent evolution. The localization of these residues occurred primarily at the interface of the upper halves of the transmembrane domains, implying that canonical positions govern odor selectivity across ORs. Altogether, our results provide a basis for translating odorants into receptor neuron responses for the unraveling of mammalian odor coding.

neuroscience↗