A cortico-collicular circuit for orienting to shelter during escape.

When faced with predatory threats, escape towards shelter is an adaptive action that offers long-term protection against the attacker. Animals rely on knowledge of safe locations in the environment to instinctively execute rapid shelter-directed escape actions1,2. Although previous work has identified neural mechanisms of escape initiation3,4, it is not known how the escape circuit incorporates spatial information to execute rapid flights along the most efficient route to shelter. Here we show that the mouse retrosplenial cortex (RSP) and superior colliculus (SC) form a circuit that encodes the shelter-direction vector and is specifically required for accurately orienting to shelter during escape. Shelter direction is encoded in RSP and SC neurons in egocentric coordinates and SC shelter-direction tuning depends on RSP activity. Inactivation of the RSP-SC pathway disrupts the orientation to shelter and causes escapes away from the optimal shelter-directed route, but does not lead to generic deficits in orientation or spatial navigation. We find that the RSP and SC are monosynaptically connected and form a feedforward lateral inhibition microcircuit that strongly drives the inhibitory collicular network because of higher RSP input convergence and synaptic integration efficiency in inhibitory SC neurons. This results in broad shelter-direction tuning in inhibitory SC neurons and sharply tuned excitatory SC neurons. These findings are recapitulated by a biologically constrained spiking network model in which RSP input to the local SC recurrent ring architecture generates a circular shelter-direction map. We propose that this RSP-SC circuit might be specialized for generating collicular representations of memorized spatial goals that are readily accessible to the motor system during escape, or more broadly, during navigation when the goal must be reached as fast as possible.

Innate heuristics and fast learning support escape route selection in mice.

When faced with imminent danger, animals must rapidly take defensive actions to reach safety. Mice can react to threatening stimuli in ∼250 milliseconds1 and, in simple environments, use spatial memory to quickly escape to shelter.2,3 Natural habitats, however, often offer multiple routes to safety that animals must identify and choose from.4 This is challenging because although rodents can learn to navigate complex mazes,5,6 learning the value of different routes through trial and error during escape could be deadly. Here, we investigated how mice learn to choose between different escape routes. Using environments with paths to shelter of varying length and geometry, we find that mice prefer options that minimize path distance and angle relative to the shelter. This strategy is already present during the first threat encounter and after only ∼10 minutes of exploration in a novel environment, indicating that route selection does not require experience of escaping. Instead, an innate heuristic assigns survival value to each path after rapidly learning the spatial environment. This route selection process is flexible and allows quick adaptation to arenas with dynamic geometries. Computational modeling shows that model-based reinforcement learning agents replicate the observed behavior in environments where the shelter location is rewarding during exploration. These results show that mice combine fast spatial learning with innate heuristics to choose escape routes with the highest survival value. The results further suggest that integrating prior knowledge acquired through evolution with knowledge learned from experience supports adaptation to changing environments and minimizes the need for trial and error when the errors are costly.

Multisensory coding of angular head velocity in the retrosplenial cortex.

To successfully navigate the environment, animals depend on their ability to continuously track their heading direction and speed. Neurons that encode angular head velocity (AHV) are fundamental to this process, yet the contribution of various motion signals to AHV coding in the cortex remains elusive. By performing chronic single-unit recordings in the retrosplenial cortex (RSP) of the mouse and tracking the activity of individual AHV cells between freely moving and head-restrained conditions, we find that vestibular inputs dominate AHV signaling. Moreover, the addition of visual inputs onto these neurons increases the gain and signal-to-noise ratio of their tuning during active exploration. Psychophysical experiments and neural decoding further reveal that vestibular-visual integration increases the perceptual accuracy of angular self-motion and the fidelity of its representation by RSP ensembles. We conclude that while cortical AHV coding requires vestibular input, where possible, it also uses vision to optimize heading estimation during navigation.

Mice learn multi-step routes by memorizing subgoal locations.

The behavioral strategies that mammals use to learn multi-step routes are unknown. In this study, we investigated how mice navigate to shelter in response to threats when the direct path is blocked. Initially, they fled toward the shelter and negotiated obstacles using sensory cues. Within 20 min, they spontaneously adopted a subgoal strategy, initiating escapes by running directly to the obstacle's edge. Mice continued to escape in this manner even after the obstacle had been removed, indicating use of spatial memory. However, standard models of spatial learning-habitual movement repetition and internal map building-did not explain how subgoal memories formed. Instead, mice used a hybrid approach: memorizing salient locations encountered during spontaneous 'practice runs' to the shelter. This strategy was also used during a geometrically identical food-seeking task. These results suggest that subgoal memorization is a fundamental strategy by which rodents learn efficient multi-step routes in new environments.

Correction: A system for tracking whisker kinematics and whisker shape in three dimensions.

[This corrects the article DOI: 10.1371/journal.pcbi.1007402.].

A system for tracking whisker kinematics and whisker shape in three dimensions.

Quantification of behaviour is essential for biology. Since the whisker system is a popular model, it is important to have methods for measuring whisker movements from behaving animals. Here, we developed a high-speed imaging system that measures whisker movements simultaneously from two vantage points. We developed a whisker tracker algorithm that automatically reconstructs 3D whisker information directly from the 'stereo' video data. The tracker is controlled via a Graphical User Interface that also allows user-friendly curation. The algorithm tracks whiskers, by fitting a 3D Bezier curve to the basal section of each target whisker. By using prior knowledge of natural whisker motion and natural whisker shape to constrain the fits and by minimising the number of fitted parameters, the algorithm is able to track multiple whiskers in parallel with low error rate. We used the output of the tracker to produce a 3D description of each tracked whisker, including its 3D orientation and 3D shape, as well as bending-related mechanical force. In conclusion, we present a non-invasive, automatic system to track whiskers in 3D from high-speed video, creating the opportunity for comprehensive 3D analysis of sensorimotor behaviour and its neural basis.

The role of the periaqueductal gray in escape behavior.

Escape behavior is a defensive action deployed by animals in response to imminent threats. In mammalian species, a variety of different brain circuits are known to participate in this crucial survival behavior. One of these circuits is the periaqueductal gray, a midbrain structure that can command a variety of instinctive behaviors. Recent experiments using modern systems neuroscience techniques have begun to elucidate the specific role of the periaqueductal gray in controlling escape. These have shown that periaqueductal gray neurons are crucial units for gating and commanding the initiation of escape, specifically activated in situations of imminent, escapable threat. In addition, it is becoming clear that the periaqueductal gray integrates brain-wide information that can modulate escape initiation to generate flexible defensive behaviors.

Prediction of Choice from Competing Mechanosensory and Choice-Memory Cues during Active Tactile Decision Making.

Perceptual decision making is an active process where animals move their sense organs to extract task-relevant information. To investigate how the brain translates sensory input into decisions during active sensation, we developed a mouse active touch task where the mechanosensory input can be precisely measured and that challenges animals to use multiple mechanosensory cues. Male mice were trained to localize a pole using a single whisker and to report their decision by selecting one of three choices. Using high-speed imaging and machine vision, we estimated whisker-object mechanical forces at millisecond resolution. Mice solved the task by a sensory-motor strategy where both the strength and direction of whisker bending were informative cues to pole location. We found competing influences of immediate sensory input and choice memory on mouse choice. On correct trials, choice could be predicted from the direction and strength of whisker bending, but not from previous choice. In contrast, on error trials, choice could be predicted from previous choice but not from whisker bending. This study shows that animal choices during active tactile decision making can be predicted from mechanosensory and choice-memory signals, and provides a new task well suited for the future study of the neural basis of active perceptual decisions.SIGNIFICANCE STATEMENT Due to the difficulty of measuring the sensory input to moving sense organs, active perceptual decision making remains poorly understood. The whisker system provides a way forward since it is now possible to measure the mechanical forces due to whisker-object contact during behavior. Here we train mice in a novel behavioral task that challenges them to use rich mechanosensory cues but can be performed using one whisker and enables task-relevant mechanical forces to be precisely estimated. This approach enables rigorous study of how sensory cues translate into action during active, perceptual decision making. Our findings provide new insight into active touch and how sensory/internal signals interact to determine behavioral choices.

What the whiskers tell the brain.

A fundamental question in the investigation of any sensory system is what physical signals drive its sensory neurons during natural behavior. Surprisingly, in the whisker system, it is only recently that answers to this question have emerged. Here, we review the key developments, focussing mainly on the first stage of the ascending pathway - the primary whisker afferents (PWAs). We first consider a biomechanical framework, which describes the fundamental mechanical forces acting on the whiskers during active sensation. We then discuss technical progress that has allowed such mechanical variables to be estimated in awake, behaving animals. We discuss past electrophysiological evidence concerning how PWAs function and reinterpret it within the biomechanical framework. Finally, we consider recent studies of PWAs in awake, behaving animals and compare the results to related studies of the cortex. We argue that understanding 'what the whiskers tell the brain' sheds valuable light on the computational functions of downstream neural circuits, in particular, the barrel cortex.

The peripheral olfactory code in Drosophila larvae contains temporal information and is robust over multiple timescales.

We studied the electrophysiological activity of two classes of Drosophila melanogaster larval olfactory sensory neurons (OSNs), Or24a and Or74a, in response to 1 s stimulation with butanol, octanol, 2-heptanone, and propyl acetate. Each odour/OSN combination produced unique responses in terms of spike count and temporal profile. We used a classifier algorithm to explore the information content of OSN activity, and showed that as well as spike count, the activity of these OSNs included temporal information that enabled the classifier to accurately identify odours. The responses of OSNs during continuous odour exposure (5 and 20 min) showed that both types of neuron continued to respond, with no complete adaptation, and with no change to their ability to encode temporal information. Finally, we exposed larvae to octanol for 3 days and found only minor quantitative changes in OSN response to odours, indicating that the larval peripheral code is robust when faced with long-term exposure to odours, such as would be found in a natural context.

Prediction of primary somatosensory neuron activity during active tactile exploration.

Primary sensory neurons form the interface between world and brain. Their function is well-understood during passive stimulation but, under natural behaving conditions, sense organs are under active, motor control. In an attempt to predict primary neuron firing under natural conditions of sensorimotor integration, we recorded from primary mechanosensory neurons of awake, head-fixed mice as they explored a pole with their whiskers, and simultaneously measured both whisker motion and forces with high-speed videography. Using Generalised Linear Models, we found that primary neuron responses were poorly predicted by whisker angle, but well-predicted by rotational forces acting on the whisker: both during touch and free-air whisker motion. These results are in apparent contrast to previous studies of passive stimulation, but could be reconciled by differences in the kinematics-force relationship between active and passive conditions. Thus, simple statistical models can predict rich neural activity elicited by natural, exploratory behaviour involving active movement of sense organs.

Microsecond-scale timing precision in rodent trigeminal primary afferents.

Communication in the nervous system occurs by spikes: the timing precision with which spikes are fired is a fundamental limit on neural information processing. In sensory systems, spike-timing precision is constrained by first-order neurons. We found that spike-timing precision of trigeminal primary afferents in rats and mice is limited both by stimulus speed and by electrophysiological sampling rate. High-speed video of behaving mice revealed whisker velocities of at least 17,000°/s, so we delivered an ultrafast "ping" (>50,000°/s) to single whiskers and sampled primary afferent activity at 500 kHz. Median spike jitter was 17.4 µs; 29% of neurons had spike jitter < 10 µs. These results indicate that the input stage of the trigeminal pathway has extraordinary spike-timing precision and very high potential information capacity. This timing precision ranks among the highest in biology.