Context-independent encoding of passive and active self-motion in vestibular afferent fibers during locomotion in primates

The vestibular system detects head motion to coordinate vital reflexes and provide our sense of balance and spatial orientation. A long-standing hypothesis has been that projections from the central vestibular system back to the vestibular sensory organs (i.e., the efferent vestibular system) mediate adaptive sensory coding during voluntary locomotion. However, direct proof for this idea has been lacking. Here we recorded from individual semicircular canal and otolith afferents during walking and running in monkeys. Using a combination of mathematical modeling and nonlinear analysis, we show that afferent encoding is actually identical across passive and active conditions, irrespective of context. Thus, taken together our results are instead consistent with the view that the vestibular periphery relays robust information to the brain during primate locomotion, suggesting that context-dependent modulation instead occurs centrally to ensure that coding is consistent with behavioral goals during locomotion.

Transcriptional adaptation of sensory neurons to GPCR identity and activity

Sensory adaptation is critical to extract information from a changing world. Taking advantage of the extensive 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 olfactory sensory neuron populations are already highly divergent, specific to the olfactory receptor they express, and are surprisingly associated with the sequence of these latter. These divergent profiles further evolve in response to the environment, as odorant exposure leads to massive reprogramming via the modulation of transcription. Adenylyl cyclase 3, but not other main elements of the olfactory transduction cascade, plays a critical role in this activity-induced transcriptional adaptation. 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 providing a novel layer of complexity to sensory coding.

Endogenous recruitment of frontal-sensory circuits during visual discrimination

A long-range circuit linking anterior cingulate cortex (ACC) to primary visual cortex (V1) has been previously proposed to mediate visual selective attention in mice during visually guided behaviour. Here we used in vivo two-photon functional imaging to measure endogenous activity of ACC neurons projecting to layer 1 of V1 (ACC-V1axons) in mice either passively viewing stimuli or performing a go/no-go visually guided task. We observed that while ACC-V1axons were recruited under these conditions, this was not linked to enhancement of neural or behavioural measures of sensory coding. Instead, ACC-V1axon activity was observed to be associated with licking behaviour, modulated by reward, and biased towards task relevant sensory cortex.

State-Dependent Synchrony and Functional Connectivity in the Primary and Secondary Whisker Somatosensory Cortices

Synchronized activity plays an important role in sensory coding and memory and is a hallmark of functional network connectivity. However, the effect of sensory activation on synchronization and cortical functional connectivity is largely unknown. In this study, we investigated the effect of whisker activation on synchronization and functional connectivity of the primary (wS1) and secondary (wS2) whisker somatosensory cortices at the single-cell level. The results showed that during the spontaneous pre-stimulus state, neurons tended to be functionally connected with nearby neurons which shared similar tuning characteristics. Whisker activation using either ramp-and-hold stimulation or artificial whisking against sandpaper has significantly reduced the average overall pairwise synchronization and functional connectivity within the wS1 barrel and wS2 cortices. Whisker stimulation disconnected approximately a third of neuronal pairs that were functionally connected during the unstimulated state. Nearby neurons with congruent tuning properties were more likely to remain functionally connected during whisker activation. The findings of this study indicated that cortical somatosensory networks are organized in non-random small world networks composed of neurons sharing relatively similar tuning properties. Sensory whisker activation intensifies these properties and further subdivides the cortical network into smaller more functionally uniform subnetworks, which possibly serve to increase the computational capacity of the network.

The sensory code within sense of time

Sensory experiences are accompanied by the perception of the passage of time; a cell phone vibration, for instance, is sensed as brief or long. The neuronal mechanisms underlying the perception of elapsed time remain unknown1. Recent work agrees on a role for cortical processing networks2,3, however the causal function of sensory cortex in time perception has not yet been specified. We hypothesize that the mechanisms for time perception are embedded within primary sensory cortex and are thus governed by the basic rules of sensory coding. By recording and optogenetically modulating neuronal activity in rat vibrissal somatosensory cortex, we find that the percept of stimulus duration is dilated and compressed by optogenetic excitation and inhibition, respectively, during stimulus delivery. A second set of rats judged the intensity of tactile stimuli; here, optogenetic excitation amplified the intensity percept, demonstrating sensory cortex to be the common gateway to both time and stimulus feature processing. The coding algorithms for sensory features are well established4–10. Guided by these algorithms, we formulated a 3–stage model beginning with the membrane currents evoked by vibrissal and optogenetic drive and culminating in the representation of perceived time; this model successfully replicated rats′ choices. Our finding that stimulus coding is intrinsic to sense of time disagrees with dedicated pacemaker-accumulator operation models11–13, where sensory input acts only to trigger the onset and offset of the timekeeping process. Time perception is thus as deeply intermeshed within the sensory processing pathway as is the sense of touch itself14,15 and can now be treated through the computational language of sensory coding. The model presented here readily generalizes to humans14,16 and opens up new approaches to understanding the time misperception at the core of numerous neurological conditions17,18.

A universal probabilistic spike count model reveals ongoing modulation of neural variability

Neural responses are variable: even under identical experimental conditions, single neuron and population responses typically differ from trial to trial and across time. Recent work has demonstrated that this variability has predictable structure, can be modulated by sensory input and behaviour, and bears critical signatures of the underlying network dynamics and computations. However, current methods for characterising neural variability are primarily geared towards sensory coding in the laboratory: they require trials with repeatable experimental stimuli and behavioural covariates. In addition, they make strong assumptions about the parametric form of variability, rely on assumption-free but data-inefficient histogram-based approaches, or are altogether ill-suited for capturing variability modulation by covariates. Here we present a universal probabilistic spike count model that eliminates these shortcomings. Our method builds on sparse Gaussian processes and can model arbitrary spike count distributions (SCDs) with flexible dependence on observed as well as latent covariates, using scalable variational inference to jointly infer the covariate-to-SCD mappings and latent trajectories in a data efficient way. Without requiring repeatable trials, it can flexibly capture covariate-dependent joint SCDs, and provide interpretable latent causes underlying the statistical dependencies between neurons. We apply the model to recordings from a canonical non-sensory neural population: head direction cells in the mouse. We find that variability in these cells defies a simple parametric relationship with mean spike count as assumed in standard models, its modulation by external covariates can be comparably strong to that of the mean firing rate, and slow low-dimensional latent factors explain away neural correlations. Our approach paves the way to understanding the mechanisms and computations underlying neural variability under naturalistic conditions, beyond the realm of sensory coding with repeatable stimuli.

Modulation Ranges of Different Sensations for Coding Electrically Evoked Tactile Sensory Feedback

The ability to perceive prosthetic grasping may enable amputees to better interact with external objects. This may require customized coding of multiple sensory feedback for each amputee. This study developed a protocol to determine optimal modulation ranges of sensations elicited by transcutaneous electrical nerve stimulation (TENS). These sensations that were referred to the lost fingers provided the possibility for restoring multi-modalities of sensory feedback for amputees with evoked tactile sensation (ETS) non-invasively. To match the restricted projected finger map area, smaller electrodes must be used to deliver electrical stimulation for multi-channel sensory information, which resulted in fewer types of sensations. Our protocol provided comprehensive information for optimal selection of amplitude and frequency in a personalized, pulse-width encoding paradigm. The good sensitivity for vibration and buzz in both able-bodied and amputee subjects suggested that perceptual intensity can be effectively modulated to convey sensory information via either of the sensations. The efficacy of this protocol in sensory coding for forearm amputees was demonstrated in finger-specific identification experiment. This protocol may allow customization of ETS-based sensory feedback with an optimal encoding strategy for individual amputees.

Modulation Ranges of Different Sensations for Coding Electrically Evoked Tactile Sensory Feedback

The ability to perceive prosthetic grasping may enable amputees to better interact with external objects. This may require customized coding of multiple sensory feedback for each amputee. This study developed a protocol to determine optimal modulation ranges of sensations elicited by transcutaneous electrical nerve stimulation (TENS). These sensations that were referred to the lost fingers provided the possibility for restoring multi-modalities of sensory feedback for amputees with evoked tactile sensation (ETS) non-invasively. To match the restricted projected finger map area, smaller electrodes must be used to deliver electrical stimulation for multi-channel sensory information, which resulted in fewer types of sensations. Our protocol provided comprehensive information for optimal selection of amplitude and frequency in a personalized, pulse-width encoding paradigm. The good sensitivity for vibration and buzz in both able-bodied and amputee subjects suggested that perceptual intensity can be effectively modulated to convey sensory information via either of the sensations. The efficacy of this protocol in sensory coding for forearm amputees was demonstrated in finger-specific identification experiment. This protocol may allow customization of ETS-based sensory feedback with an optimal encoding strategy for individual amputees.