The primary somatosensory cortex (S1) plays a critical role in processing multiple somatosensations, but the mechanism underlying the representation of different submodalities of somatosensation in S1 remains unclear. Using in vivo two-photon calcium imaging that simultaneously monitors hundreds of layer 2/3 pyramidal S1 neurons of awake male mice, we examined neuronal responses triggered by mechanical, thermal or pruritic stimuli. We found that mechanical, thermal and pruritic stimuli activated largely overlapping neuronal populations in the same somatotopic S1 subregion. Population decoding analysis revealed that the local neuronal population in S1 encoded sufficient information to distinguish different somatosensory submodalities. Although multimodal S1 neurons responding to multiple types of stimuli exhibited no spatial clustering, S1 neurons preferring mechanical and thermal stimuli tended to show local clustering. These findings demonstrated the coding scheme of different submodalities of somatosensa...

Brain-machine interfaces (BMIs) for reaching have enjoyed continued performance improvements, yet there remains significant need for BMIs that control other movement classes. Recent scientific findings suggest that the intrinsic covariance structure of neural activity depends strongly on movement class, potentially necessitating different decode algorithms across classes. To address this possibility, we developed a self-motion BMI based on cortical activity as monkeys cycled a hand-held pedal to progress along a virtual track. Unlike during reaching, we found no high-variance dimensions that directly correlated with to-be-decoded variables. This was due to no neurons having consistent correlations between their responses and kinematic variables. Yet we could decode a single variable – self-motion – by non-linearly leveraging structure that spanned multiple high-variance neural dimensions. Resulting online BMI-control success rates approached those during manual control. These findings make two broad points...

Multisensory plasticity enables our senses to dynamically adapt to each other and the external environment, a fundamental operation that our brain performs continuously. We searched for neural correlates of adult multisensory plasticity in the dorsal medial superior temporal area (MSTd) and the ventral intraparietal area (VIP) in two male rhesus macaques using a paradigm of supervised calibration. We report little plasticity in neural responses in the relatively low-level multisensory cortical area MSTd. In contrast, neural correlates of plasticity are found in higher level multisensory VIP, an area with strong decision-related activity. Accordingly, we observed systematic shifts of VIP tuning curves, which were reflected in the choice-related component of the population response. This is the first demonstration of neuronal calibration, together with behavioral calibration, in single sessions. These results lay the foundation for understanding multisensory neural plasticity, applicable broadly to maintaini...

Narrative comprehension involves a constant interplay of the accumulation of incoming events and their integration into a coherent structure. This study characterizes cognitive states during narrative comprehension and the network-level reconfiguration occurring dynamically in the functional brain. We presented movie clips of temporally scrambled sequences to human participants (male and female), eliciting fluctuations in the subjective feeling of comprehension. Comprehension occurred when processing events that were highly causally related to the previous events, suggesting that comprehension entails the integration of narratives into a causally coherent structure. The functional neuroimaging results demonstrated that the integrated and efficient brain state emerged during the moments of narrative integration with the increased level of activation and across-modular connections in the default mode network. Underlying brain states were synchronized across individuals when comprehending novel narratives, wi...

Recent large genome-wide association studies have identified multiple confident risk loci linked to addiction-associated behavioral traits. Most genetic variants linked to addiction-associated traits lie in noncoding regions of the genome, likely disrupting cis -regulatory element (CRE) function. CREs tend to be highly cell type-specific and may contribute to the functional development of the neural circuits underlying addiction. Yet, a systematic approach for predicting the impact of risk variants on the CREs of specific cell populations is lacking. To dissect the cell types and brain regions underlying addiction-associated traits, we applied stratified linkage disequilibrium score regression to compare genome-wide association studies to genomic regions collected from human and mouse assays for open chromatin, which is associated with CRE activity. We found enrichment of addiction-associated variants in putative CREs marked by open chromatin in neuronal (NeuN+) nuclei collected from multiple prefrontal co...

Cortical parvalbumin-expressing (Pvalb+) neurons provide robust inhibition to neighboring pyramidal neurons, crucial for the proper functioning of cortical networks. This class of inhibitory neurons undergoes extensive synaptic formation and maturation during the first weeks after birth and continue to dynamically maintain their synaptic output throughout adulthood. While several transcription factors, such as Nkx2-1, Lhx6, and Sox6, are known to be necessary for the differentiation of progenitors into Pvalb+ neurons, which transcriptional programs underlie the postnatal maturation and maintenance of Pvalb+ neurons' innervation and synaptic function remains largely unknown. Because Sox6 is continuously expressed in Pvalb+ neurons until adulthood, we used conditional knock-out strategies to investigate its putative role in the postnatal maturation and synaptic function of cortical Pvalb+ neurons in mice of both sexes. We found that early postnatal loss of Sox6 in Pvalb+ neurons leads to failure of synaptic ...

Mohammed Al-Yaari, Chikao Onogi, Rei Yamada, Ryota Adachi, Daiya Kondo, et al. (see pages [8904–8916][1]) Animals can localize sounds by comparing the time at which sounds reach each ear. In birds, this comparison relies on precise spike timing in the nucleus magnocellularis (NM), which receives

Na+ sensitivity is a unique feature of Na+-activated K+ (KNa) channels, making them naturally suited to counter a sudden influx in Na+ ions. As such, it has long been suggested that KNa channels may serve a protective function against excessive excitation associated with neuronal injury and disease. This hypothesis, however, has remained largely untested. Here, we examine KNa channels encoded by the Drosophila Slo2 ( dSlo2 ) gene in males and females. We show that dSlo2/KNa channels are selectively expressed in cholinergic neurons in the adult brain, as well as in glutamatergic motor neurons, where dampening excitation may function to inhibit global hyperactivity and seizure-like behavior. Indeed, we show that effects of feeding Drosophila a cholinergic agonist are exacerbated by the loss of dSlo2/KNa channels. Similar to mammalian Slo2/KNa channels, we show that dSlo2/KNa channels encode a TTX-sensitive K+ conductance, indicating that dSlo2/KNa channels can be activated by Na+ carried by voltage-dependent...

Previous studies have shown that self-generated stimuli in auditory, visual, and somatosensory domains are attenuated, producing decreased behavioral and neural responses compared with the same stimuli that are externally generated. Yet, whether such attenuation also occurs for higher-level cognitive functions beyond sensorimotor processing remains unknown. In this study, we assessed whether cognitive functions such as numerosity estimations are subject to attenuation in 56 healthy participants (32 women). We designed a task allowing the controlled comparison of numerosity estimations for self-generated (active condition) and externally generated (passive condition) words. Our behavioral results showed a larger underestimation of self-generated compared with externally generated words, suggesting that numerosity estimations for self-generated words are attenuated. Moreover, the linear relationship between the reported and actual number of words was stronger for self-generated words, although the ability to...