Reports indicate an association between COVID-19 and anosmia, as well as the presence of SARS-CoV-2 virions in the olfactory bulb. To test whether the olfactory neuroepithelium may represent a target of the virus, we generated RNAseq libraries from human olfactory neuroepithelia, in which we found substantial expression of the genes coding for the virus receptor angiotensin-converting enzyme-2 (ACE2) and for the virus internalization enhancer TMPRSS2. We analyzed a human olfactory single-cell RNA-seq dataset and determined that sustentacular cells, which maintain the integrity of olfactory sensory neurons, express ACE2 and TMPRSS2. ACE2 protein was highly expressed in a subset of sustentacular cells in human and mouse olfactory tissues. Finally, we found ACE2 transcripts in specific brain cell types, both in mice and humans. Sustentacular cells thus represent a potential entry door for SARS-CoV-2 in a neuronal sensory system that is in direct connection with the brain.

The recent emergence of the pathogenic SARS-CoV-2 initiated a worldwide health crisis. The entry of the virus into cells is mediated by the binding of the viral Spike protein to the angiotensin-converting enzyme-2 (ACE2), followed by its priming by the TMPRSS2 serine protease, both present on the cellular membrane of the target cells. In the respiratory tract, these targets are ciliated cells. Interestingly, various reports indicate an association between SARS-CoV-2 infection and anosmia, suggesting an alteration not restricted to the respiratory tissue, but that might also include the olfactory sensory epithelium. We explored this possibility by generating RNA-seq libraries from human neuroepithelium, in which we found significant expression of ACE2 and TMPRSS2. To determine whether specific cell types of this chemosensory tissue may coexpress both of the virus entry genes, we analyzed a scRNA-seq dataset. We determined that sustentacular cells, which are in direct contact with the external world and maintain the integrity of olfactory sensory neurons, represents a prime candidate for SARS-CoV-2 infection via the nose, and possibly for SARS-CoV-2-induced anosmia.

In various mental disorders, dysfunction of the prefrontal cortex contributes to cognitive deficits. Here we studied how the claustrum (CLA), a nucleus sharing reciprocal connections with the cortex, may participate in these cognitive impairments. We show that specific ensembles of CLA and of medial prefrontal cortex (mPFC) neurons are activated during a task requiring cognitive control such as attentional set-shifting, i.e. the ability to shift attention towards newly relevant stimulus-reward associations while disengaging from irrelevant ones. CLA neurons exert a direct excitatory input on mPFC pyramidal cells, and chemogenetic inhibition of CLA neurons suppresses the formation of specific mPFC assemblies during attentional set-shifting. Furthermore, impairing the recruitment of specific CLA assemblies through opto/chemogenetic manipulations prevents attentional set-shifting. In conclusion, we propose that the CLA controls the reorganization of mPFC ensembles to enable attentional set-shifting, emphasizing a potential role of the CLA-mPFC network in attentional dysfunctions.

Generation of surrogate cells with stable functional identities is crucial for developing cell-based therapies. Efforts to produce insulin-secreting replacement cells to treat diabetes require reliable tools to assess islet cellular identity. Here, we conduct a thorough single-cell transcriptomics meta-analysis to identify robustly expressed markers used to build genesets describing the identity of human α-, β-, γ- and δ-cells. These genesets define islet cellular identities better than previously published genesets. We show their efficacy to outline cell identity changes and unravel some of their underlying genetic mechanisms, whether during embryonic pancreas development or in experimental setups aiming at developing glucose-responsive insulin-secreting cells, such as pluripotent stem-cell differentiation or in adult islet cell reprogramming protocols. These islet cell type-specific genesets represent valuable tools that accurately benchmark gain and loss in islet cell identity traits.

Neural models of anatomical and functional alterations have been proposed for bipolar disorders (BD). However, studies in affected patients do not allow disentangling alterations linked to the liability to BD from those associated with the evolution, medication and comorbidities of BD. Explorations in high risk subjects allow the study of these risk markers. We reported and summarized all functional magnetic resonance imaging (fMRI) studies focusing on first-degree relatives of BD patients. We found 29 studies reporting neural correlates of working memory (WM), emotional processing, executive functions and resting state in relatives of BD patients, compared to healthy subjects. Overall, the same regions that have been involved in patients, such as the inferior frontal gyrus and limbic areas, seem to be functionally altered in high-risk subjects. We conclude that the same brain regions already implicated in the pathophysiology of the disease such as the amygdala are also associated with the risk of BD. However longitudinal studies are required to understand their implication in the transition to BD.

Neurons in primary sensory cortex encode a variety of stimulus features upon perceptual learning. However, it is unclear whether the acquired stimulus selectivity remains stable when the same input is perceived in a different context. Here, we monitor the activity of individual neurons in the mouse primary somatosensory cortex during reward-based texture discrimination. We track their stimulus selectivity before and after changing reward contingencies, which allows us to identify various classes of neurons. We find neurons that stably represented a texture or the upcoming behavioral choice, but the majority is dynamic. Among those, a subpopulation of neurons regains texture selectivity contingent on the associated reward value. These value-sensitive neurons forecast the onset of learning by displaying a distinct and transient increase in activity, depending on past behavioral experience. Thus, stimulus selectivity of excitatory neurons during perceptual learning is dynamic and largely relies on behavioral contingencies, even in primary sensory cortex.

In mammals, chemoperception relies on a diverse set of neuronal sensors able to detect chemicals present in the environment, and to adapt to various levels of stimulation. The contribution of endogenous and external factors to these neuronal identities remains to be determined. Taking advantage of the parallel coding lines present in the olfactory system, we explored the potential variations of neuronal identities before and after olfactory experience. We found that at rest, the transcriptomic profiles of mouse olfactory sensory neuron populations are already divergent, specific to the olfactory receptor they express, and are associated with the sequence of these latter. These divergent profiles further evolve in response to the environment, as odorant exposure leads to reprogramming via the modulation of transcription. These findings highlight a broad range of sensory neuron identities that are present at rest and that adapt to the experience of the individual, thus adding to the complexity and flexibility of sensory coding.

Neurons in primary sensory cortex encode a variety of stimulus features upon perceptual learning. However, it is unclear whether the acquired stimulus selectivity remains stable when the same input is perceived in a different context. Here, we monitored the activity of individual neurons in the mouse primary somatosensory cortex in a reward-based texture discrimination task. We tracked their stimulus selectivity before and after changing reward contingencies and found that many neurons are dynamically selective. A subpopulation of neurons regains selectivity contingent on stimulus-value. These value-sensitive neurons forecast the onset of learning by displaying a distinct and transient increase in activity, depending on past behavioral experience. Thus, stimulus encoding during perceptual learning is dynamic and largely relies on behavioral contingencies, even in primary sensory cortex.