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

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely