Early selection of task-relevant features through population gating.

Brains can gracefully weed out irrelevant stimuli to guide behavior. This feat is believed to rely on a progressive selection of task-relevant stimuli across the cortical hierarchy, but the specific across-area interactions enabling stimulus selection are still unclear. Here, we propose that population gating, occurring within primary auditory cortex (A1) but controlled by top-down inputs from prelimbic region of medial prefrontal cortex (mPFC), can support across-area stimulus selection. Examining single-unit activity recorded while rats performed an auditory context-dependent task, we found that A1 encoded relevant and irrelevant stimuli along a common dimension of its neural space. Yet, the relevant stimulus encoding was enhanced along an extra dimension. In turn, mPFC encoded only the stimulus relevant to the ongoing context. To identify candidate mechanisms for stimulus selection within A1, we reverse-engineered low-rank RNNs trained on a similar task. Our analyses predicted that two context-modulated neural populations gated their preferred stimulus in opposite contexts, which we confirmed in further analyses of A1. Finally, we show in a two-region RNN how population gating within A1 could be controlled by top-down inputs from PFC, enabling flexible across-area communication despite fixed inter-areal connectivity.

Self-propulsion of inverse Leidenfrost drops on a cryogenic bath.

When deposited on a hot bath, volatile drops are observed to stay in levitation: the so-called Leidenfrost effect. Here, we discuss drop dynamics in an inverse Leidenfrost situation where room-temperature drops are deposited on a liquid-nitrogen pool and levitate on a vapor film generated by evaporation of the bath. In the seconds following deposition, we observe that the droplets start to glide on the bath along a straight path, only disrupted by elastic bouncing close to the edges of the container. Initially at rest, these self-propelled drops accelerate within a few seconds and reach velocities on the order of a few centimeters per second before slowing down on a longer time scale. They remain self-propelled as long as they are sitting on the bath, even after freezing and cooling down to liquid-nitrogen temperature. We experimentally investigate the parameters that affect liquid motion and propose a model, based on the experimentally and numerically observed (stable) symmetry breaking within the vapor film that supports the drop. When the film thickness and the cooling dynamics of the drops are also modeled, the variations of the drop velocities can be accurately reproduced.

Whole-Brain Calcium Imaging during Physiological Vestibular Stimulation in Larval Zebrafish.

The vestibular apparatus provides animals with postural and movement-related information that is essential to adequately execute numerous sensorimotor tasks. In order to activate this sensory system in a physiological manner, one needs to macroscopically rotate or translate the animal's head, which in turn renders simultaneous neural recordings highly challenging. Here we report on a novel miniaturized, light-sheet microscope that can be dynamically co-rotated with a head-restrained zebrafish larva, enabling controlled vestibular stimulation. The mechanical rigidity of the microscope allows one to perform whole-brain functional imaging with state-of-the-art resolution and signal-to-noise ratio while imposing up to 25° in angular position and 6,000°/s2 in rotational acceleration. We illustrate the potential of this novel setup by producing the first whole-brain response maps to sinusoidal and stepwise vestibular stimulation. The responsive population spans multiple brain areas and displays bilateral symmetry, and its organization is highly stereotypic across individuals. Using Fourier and regression analysis, we identified three major functional clusters that exhibit well-defined phasic and tonic response patterns to vestibular stimulation. Our rotatable light-sheet microscope provides a unique tool for systematically studying vestibular processing in the vertebrate brain and extends the potential of virtual-reality systems to explore complex multisensory and motor integration during simulated 3D navigation.

An open-source high-speed infrared videography database to study the principles of active sensing in freely navigating rodents.

Background: Active sensing is crucial for navigation. It is characterized by self-generated motor action controlling the accessibility and processing of sensory information. In rodents, active sensing is commonly studied in the whisker system. As rats and mice modulate their whisking contextually, they employ frequency and amplitude modulation. Understanding the development, mechanisms, and plasticity of adaptive motor control will require precise behavioral measurements of whisker position. Findings: Advances in high-speed videography and analytical methods now permit collection and systematic analysis of large datasets. Here, we provide 6,642 videos as freely moving juvenile (third to fourth postnatal week) and adult rodents explore a stationary object on the gap-crossing task. The dataset includes sensory exploration with single- or multi-whiskers in wild-type animals, serotonin transporter knockout rats, rats received pharmacological intervention targeting serotonergic signaling. The dataset includes varying background illumination conditions and signal-to-noise ratios (SNRs), ranging from homogenous/high contrast to non-homogenous/low contrast. A subset of videos has been whisker and nose tracked and are provided as reference for image processing algorithms. Conclusions: The recorded behavioral data can be directly used to study development of sensorimotor computation, top-down mechanisms that control sensory navigation and whisker position, and cross-species comparison of active sensing. It could also help to address contextual modulation of active sensing during touch-induced whisking in head-fixed vs freely behaving animals. Finally, it provides the necessary data for machine learning approaches for automated analysis of sensory and motion parameters across a wide variety of signal-to-noise ratios with accompanying human observer-determined ground-truth.

High-precision spatial localization of mouse vocalizations during social interaction.

Mice display a wide repertoire of vocalizations that varies with age, sex, and context. Especially during courtship, mice emit ultrasonic vocalizations (USVs) of high complexity, whose detailed structure is poorly understood. As animals of both sexes vocalize, the study of social vocalizations requires attributing single USVs to individuals. The state-of-the-art in sound localization for USVs allows spatial localization at centimeter resolution, however, animals interact at closer ranges, involving tactile, snout-snout exploration. Hence, improved algorithms are required to reliably assign USVs. We develop multiple solutions to USV localization, and derive an analytical solution for arbitrary vertical microphone positions. The algorithms are compared on wideband acoustic noise and single mouse vocalizations, and applied to social interactions with optically tracked mouse positions. A novel, (frequency) envelope weighted generalised cross-correlation outperforms classical cross-correlation techniques. It achieves a median error of ~1.4 mm for noise and ~4-8.5 mm for vocalizations. Using this algorithms in combination with a level criterion, we can improve the assignment for interacting mice. We report significant differences in mean USV properties between CBA mice of different sexes during social interaction. Hence, the improved USV attribution to individuals lays the basis for a deeper understanding of social vocalizations, in particular sequences of USVs.

Reduced Inhibition within Layer IV of Sert Knockout Rat Barrel Cortex is Associated with Faster Sensory Integration.

Neural activity is essential for the maturation of sensory systems. In the rodent primary somatosensory cortex (S1), high extracellular serotonin (5-HT) levels during development impair neural transmission between the thalamus and cortical input layer IV (LIV). Rodent models of impaired 5-HT transporter (SERT) function show disruption in their topological organization of S1 and in the expression of activity-regulated genes essential for inhibitory cortical network formation. It remains unclear how such alterations affect the sensory information processing within cortical LIV. Using serotonin transporter knockout (Sert-/-) rats, we demonstrate that high extracellular serotonin levels are associated with impaired feedforward inhibition (FFI), fewer perisomatic inhibitory synapses, a depolarized GABA reversal potential and reduced expression of KCC2 transporters in juvenile animals. At the neural population level, reduced FFI increases the excitatory drive originating from LIV, facilitating evoked representations in the supragranular layers II/III. The behavioral consequence of these changes in network excitability is faster integration of the sensory information during whisker-based tactile navigation, as Sert-/- rats require fewer whisker contacts with tactile targets and perform object localization with faster reaction times. These results highlight the association of serotonergic homeostasis with formation and excitability of sensory cortical networks, and consequently with sensory perception.

A novel inhibitory nucleo-cortical circuit controls cerebellar Golgi cell activity.

The cerebellum, a crucial center for motor coordination, is composed of a cortex and several nuclei. The main mode of interaction between these two parts is considered to be formed by the inhibitory control of the nuclei by cortical Purkinje neurons. We now amend this view by showing that inhibitory GABA-glycinergic neurons of the cerebellar nuclei (CN) project profusely into the cerebellar cortex, where they make synaptic contacts on a GABAergic subpopulation of cerebellar Golgi cells. These spontaneously firing Golgi cells are inhibited by optogenetic activation of the inhibitory nucleo-cortical fibers both in vitro and in vivo. Our data suggest that the CN may contribute to the functional recruitment of the cerebellar cortex by decreasing Golgi cell inhibition onto granule cells.

Cerebellum involvement in cortical sensorimotor circuits for the control of voluntary movements.

Sensorimotor integration is crucial to perception and motor control. How and where this process takes place in the brain is still largely unknown. Here we analyze the cerebellar contribution to sensorimotor integration in the whisker system of mice. We identify an area in the cerebellum where cortical sensory and motor inputs converge at the cellular level. Optogenetic stimulation of this area affects thalamic and motor cortex activity, alters parameters of ongoing movements and thereby modifies qualitatively and quantitatively touch events against surrounding objects. These results shed light on the cerebellum as an active component of sensorimotor circuits and show the importance of sensorimotor cortico-cerebellar loops in the fine control of voluntary movements.

Functional role of the cerebellum in gamma-band synchronization of the sensory and motor cortices.

The cerebellum is an essential structure for the control of movement. It sends abundant ascending projections to the cerebral cortex via the thalamus, but its contribution to cortical activity remains largely unknown. Here we studied its influence on cortical neuronal activity in freely moving rats. We demonstrate an excitatory action of the cerebellum on the motor thalamus and the motor cortex. We also show that cerebellar inactivation disrupts the gamma-band coherence of local field potential between the sensory and motor cortices during whisking. In contrast, phase locking of neuronal activities to local gamma oscillations was preserved in the sensory and motor cortices by cerebellar inactivation. These results indicate that the cerebellum contributes to coordinated sensorimotor cortical activities during motor activation and thus participates in the multiregional cortical processing of information.

Sensory map transfer to the neocortex relies on pretarget ordering of thalamic axons.

Sensory maps, such as the representation of mouse facial whiskers, are conveyed throughout the nervous system by topographic axonal projections that preserve neighboring relationships between adjacent neurons. In particular, the map transfer to the neocortex is ensured by thalamocortical axons (TCAs), whose terminals are topographically organized in response to intrinsic cortical signals. However, TCAs already show a topographic order early in development, as they navigate toward their target. Here, we show that this preordering of TCAs is required for the transfer of the whisker map to the neocortex. Using Ebf1 conditional inactivation that specifically perturbs the development of an intermediate target, the basal ganglia, we scrambled TCA topography en route to the neocortex without affecting the thalamus or neocortex. Notably, embryonic somatosensory TCAs were shifted toward the visual cortex and showed a substantial intermixing along their trajectory. Somatosensory TCAs rewired postnatally to reach the somatosensory cortex but failed to form a topographic anatomical or functional map. Our study reveals that sensory map transfer relies not only on positional information in the projecting and target structures but also on preordering of axons along their trajectory, thereby opening novel perspectives on brain wiring.

Transient signals trigger synchronous bursts in an identified population of neurons.

It is an important task in neuroscience to find general principles that relate neural codes to the structure of the signals they encode. The structure of sensory signals can be described in many ways, but one important categorization distinguishes continuous from transient signals. We used the communication signals of the weakly electric fish to reveal how transient signals (chirps) can be easily distinguished from the continuous signal they disrupt. These communication signals-low-frequency sinusoids interrupted by high-frequency transients-were presented to pyramidal cells of the electrosensory lateral line lobe (ELL) during in vivo recordings. We show that a specific population of electrosensory neurons encodes the occurrence of the transient signal by synchronously producing a burst of spikes, whereas bursting was neither common nor synchronous in response to the continuous signal. We also confirmed that burst can be triggered by low-frequency modulations typical of prey signals. However, these bursts are more common in a different segment of the ELL and during spatially localized stimulation. These localized stimuli will elicit synchronized bursting only in a restricted number of cells the receptive fields of which overlap the spatial extent of the stimulus. Therefore the number of cells simultaneously producing a burst and the ELL segment responding most strongly may carry the information required to disambiguate chirps from prey signals. Finally we show that the burst response to chirps is due to a biophysical mechanism previously characterized by in vitro studies of electrosensory neurons. We conclude that bursting and synchrony across cells are important mechanisms used by sensory neurons to carry the information about behaviorally relevant but transient signals.