A midbrain mechanism for computing escape decisions in the mouse

Animals face frequent threats from predators and must generate appropriate behavioural responses to ensure their survival. To achieve this, they process sensory cues to correctly identify the presence and imminence of a predatory threat, and transform this information into defensive actions. However, despite much research in identifying the circuits that may be responsible for such transformations, little is known about how this occurs mechanistically. We focus on how escape behaviour in the mouse is generated from visual predatory threats, and use a combination of behavioural, neurophysiological and anatomical methods to identify the relevant neurons and understand how they perform this computation. In this work, we developed an innate decision making paradigm in which a mouse detects and assesses sensory stimuli of varying threat evidence during exploration, choosing whether to escape to a shelter, or not. The performance data in this task were best formalised with a drift-diffusion model of decision making, providing a framework to understand innate behavioural tasks in terms of evidence accumulation and boundaries. Next, we performed calcium imaging in freely-moving mice to probe for neural correlates of decision elements and flight behaviour in brain areas that we show to be necessary for the flight responses: we found that VGluT2 neurons in the deeper medial superior colliculus (dmSC) increase their activity during a repeated threatening stimulus, while VGluT2 neurons of the dorsolateral periaqueductal gray (dPAG) are silent until just before the initiation of escape, and are maximally active during escape. These results suggest that the dmSC accumulates evidence of threat which dPAG neurons threshold. This interpretation is supported by optogenetic activation of mSC-VGluT2 neurons in vivo, which recapitulates the statistics of escape probability evoked with a visual stimulus, while activation of VGluT2 neurons in the dPAG evokes an all-or-nothing escape response. Finally, using channelrhodopsin-2-assisted circuit mapping and monosynaptic viral tracing, we reveal that over half of dPAG-VGluT2 neurons receive monosynaptic connections from mSC-VGluT2 neurons with a low probability of release, allowing this synapse to act as a high-pass filter and providing a mechanism for the computation of an escape decision. These findings advance our understanding of how defensive behaviours are generated at circuit and single-cell level, and of how neurons process information in a circuit critical for implementing basic behaviours

Combined behavioral and neural investigations of pup retrieval

The ability to adequately adapt to a dramatically changing environment is crucial for an animal’s survival. When female mice give birth to their offspring, their environment changes drastically and they immediately need to care for the offspring, thereby ensuring the offspring’s wellbeing. Pups completely transform the environment around the mouse, triggering a number of new behaviors, as they provide a slew of new sensory inputs, including tactile and olfactory, but also auditory. Pups emit ultrasonic vocalizations (USVs) when isolated outside the nest, triggering retrieval behavior in mothers (MTs). After pups have returned to the nest and are cared for, the USV emission ceases. Interestingly, not only MTs but also virgin mice can perform pup retrieval, provided that they either have experience with pups in their home cage or are repeatedly exposed to pups in a pup retrieval task. Those two animal groups are referred to as experienced (EVs) and naive virgins (NVs). Studies have shown that excitatory neurons in the auditory cortex of MTs and EVs respond more strongly to pup calls over time. However, these studies have been performed under head-restrained unnatural conditions. Here, we provide a framework in which MTs, EVs and NVs retrieve pups in a semi-natural, freely behaving setting. During the experiment, they carry a head-mounted miniscope that allows for imaging neural activity in multiple neurons in the auditory cortex. The entire multisensory scenery is therefore accessible to mice, which was shown to impact auditory responses to pup calls. In our study, we show differences in behavioral performances of these three groups, with MTs displaying the most skilled and fine-tuned pup retrieval behavior, already highly effective during the final pregnancy stage. EVs show slightly reduced pup retrieval abilities, but superior to NVs, which retrieve pups effectively only after a few days. Additionally, we discovered that not only pups emitted USVs, but also adult mice vocalized. Intriguingly, they vocalized significantly more when pups were present in the behavioral arena, as compared to when they were alone. Clear pup call responsive neurons in the auditory cortex of all groups were scarce. Nevertheless, the overall neuronal population showed significant responses to pup calls at least in MTs, less so in EVs and least pronounced in NVs. Strikingly, other more global and behaviorally relevant events, such as pup retrievals and nest entries and exits, showed a distinct neural signature. Despite the scarcity of clear single cell responses to pup calls, the population of auditory cortex neurons carried information about pup call presence throughout all sessions in all groups, measured by a decoding analysis. This population code could be described as a sparse and dynamic code containing a few highly informative neurons, i.e. high weight neurons, that carried most of the decoding weight in a given session. This sparsity was most pronounced in MTs and least so in NVs. Besides, these high weight neurons were largely non-overlapping with high weight neurons for other non-pup call related event types. When relating single trial pup call decoding accuracies with the associated behavioral performance in a given trial, we could identify a significant relationship in EVs that was absent in MTs and NVs, suggesting that improved single trial decoding accuracies were linked to improved pup retrieval abilities. Altogether, this study shows how different pup exposure regimes can affect the learning of an essential offspring caring behavior and, that these different learning types differently enhance the neural representations of associated sensory cues

Measuring Behavior 2018 Conference Proceedings

These proceedings contain the papers presented at Measuring Behavior 2018, the 11th International Conference on Methods and Techniques in Behavioral Research. The conference was organised by Manchester Metropolitan University, in collaboration with Noldus Information Technology. The conference was held during June 5th – 8th, 2018 in Manchester, UK. Building on the format that has emerged from previous meetings, we hosted a fascinating program about a wide variety of methodological aspects of the behavioral sciences. We had scientific presentations scheduled into seven general oral sessions and fifteen symposia, which covered a topical spread from rodent to human behavior. We had fourteen demonstrations, in which academics and companies demonstrated their latest prototypes. The scientific program also contained three workshops, one tutorial and a number of scientific discussion sessions. We also had scientific tours of our facilities at Manchester Metropolitan Univeristy, and the nearby British Cycling Velodrome. We hope this proceedings caters for many of your interests and we look forward to seeing and hearing more of your contributions