Mice and rats achieve similar levels of performance in an adaptive decision-making task

Two opposing constraints exist when choosing a model organism for studying the neural basis of adaptive decision-making: (1) experimental access and (2) behavioral complexity. Available molecular and genetic approaches for studying neural circuits in the mouse fulfill the first requirement. In contrast, it is still under debate if mice can perform cognitive tasks of sufficient complexity. Here we compare learning and performance of mice and rats, the preferred behavioral rodent model, during an acoustic flexible categorization two-alternative choice task. The task required animals to switch between two categorization definitions several times within a behavioral session. We found that both species achieved similarly high performance levels. On average, rats learned the task faster than mice, although some mice were as fast as the average rat. No major differences in subjective categorization boundaries or the speed of adaptation between the two species were found. Our results demonstrate that mice are an appropriate model for the study of the neural mechanisms underlying adaptive decision-making, and suggest they might be suitable for other cognitive tasks as well

Auditory Thalamus and Auditory Cortex Are Equally Modulated by Context during Flexible Categorization of Sounds

In a dynamic world, animals must adapt rapidly to changes in the meaning of environmental cues. Such changes can influence the neural representation of sensory stimuli. Previous studies have shown that associating a stimulus with a reward or punishment can modulate neural activity in the auditory cortex (AC) and its thalamic input, the medial geniculate body (MGB). However, it is not known whether changes in stimulus-action associations alone can also modulate neural responses in these areas. We designed a categorization task for rats in which the boundary that separated low- from high-frequency sounds varied several times within a behavioral session, thus allowing us to manipulate the action associated with some sounds without changing the associated reward. We developed a computational model that accounted for the rats' performance and compared predictions from this model with sound-evoked responses from single neurons in AC and MGB in animals performing this task. We found that the responses of 15% of AC neurons and 16% of MGB neurons were modulated by changes in stimulus-action association and that the magnitude of the modulation was comparable between the two brain areas. Our results suggest that the AC and thalamus play only a limited role in mediating changes in associations between acoustic stimuli and behavioral responses

Linearity of cortical receptive fields measured with natural sounds

How do cortical neurons represent the acoustic environment? This question is often addressed by probing with simple stimuli such as clicks or tone pips. Such stimuli have the advantage of yielding easily interpreted answers, but have the disadvantage that they may fail to uncover complex or higher-order neuronal response properties. Here, we adopt an alternative approach, probing neuronal responses with complex acoustic stimuli, including animal vocalizations. We used in vivo whole-cell methods in the rat auditory cortex to record subthreshold membrane potential fluctuations elicited by these stimuli. Most neurons responded robustly and reliably to the complex stimuli in our ensemble. Using regularization techniques, we estimated the linear component, the spectrotemporal receptive field (STRF), of the transformation from the sound (as represented by its time-varying spectrogram) to the membrane potential of the neuron. We find that the STRF has a rich dynamical structure, including excitatory regions positioned in general accord with the prediction of the classical tuning curve. However, whereas the STRF successfully predicts the responses to some of the natural stimuli, it surprisingly fails completely to predict the responses to others; on average, only 11% of the response power could be predicted by the STRF. Therefore, most of the response of the neuron cannot be predicted by the linear component, although the response is deterministically related to the stimulus. Analysis of the systematic errors of the STRF model shows that this failure cannot be attributed to simple nonlinearities such as adaptation to mean intensity, rectification, or saturation. Rather, the highly nonlinear response properties of auditory cortical neurons must be attributable to nonlinear interactions between sound frequencies and time-varying properties of the neural encoder

PINP: a new method of tagging neuronal populations for identification during in vivo electrophysiological recording

Neural circuits are exquisitely organized, consisting of many different neuronal subpopulations. However, it is difficult to assess the functional roles of these subpopulations using conventional extracellular recording techniques because these techniques do not easily distinguish spikes from different neuronal populations. To overcome this limitation, we have developed PINP (Photostimulation-assisted Identification of Neuronal Populations), a method of tagging neuronal populations for identification during in vivo electrophysiological recording. The method is based on expressing the light-activated channel channelrhodopsin-2 (ChR2) to restricted neuronal subpopulations. ChR2-tagged neurons can be detected electrophysiologically in vivo since illumination of these neurons with a brief flash of blue light triggers a short latency reliable action potential. We demonstrate the feasibility of this technique by expressing ChR2 in distinct populations of cortical neurons using two different strategies. First, we labeled a subpopulation of cortical neurons-mainly fast-spiking interneurons-by using adeno-associated virus (AAV) to deliver ChR2 in a transgenic mouse line in which the expression of Cre recombinase was driven by the parvalbumin promoter. Second, we labeled subpopulations of excitatory neurons in the rat auditory cortex with ChR2 based on projection target by using herpes simplex virus 1 (HSV1), which is efficiently taken up by axons and transported retrogradely; we find that this latter population responds to acoustic stimulation differently from unlabeled neurons. Tagging neurons is a novel application of ChR2, used in this case to monitor activity instead of manipulating it. PINP can be readily extended to other populations of genetically identifiable neurons, and will provide a useful method for probing the functional role of different neuronal populations in vivo

Sonographic detection of fetal extrathoracic pulmonary sequestration.

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135413/1/jum198655283.pd

Rosetta Brains: A Strategy for Molecularly-Annotated Connectomics

We propose a neural connectomics strategy called Fluorescent In-Situ Sequencing of Barcoded Individual Neuronal Connections (FISSEQ-BOINC), leveraging fluorescent in situ nucleic acid sequencing in fixed tissue (FISSEQ). FISSEQ-BOINC exhibits different properties from BOINC, which relies on bulk nucleic acid sequencing. FISSEQ-BOINC could become a scalable approach for mapping whole-mammalian-brain connectomes with rich molecular annotations

Quadratic optimal functional quantization of stochastic processes and numerical applications

In this paper, we present an overview of the recent developments of functional quantization of stochastic processes, with an emphasis on the quadratic case. Functional quantization is a way to approximate a process, viewed as a Hilbert-valued random variable, using a nearest neighbour projection on a finite codebook. A special emphasis is made on the computational aspects and the numerical applications, in particular the pricing of some path-dependent European options.Comment: 41 page

The Burnout Epidemic Within A Viral Pandemic: Impact of a Wellness Initiative

Background: Anesthesiologists are at high risk of developing burnout, a condition which can lead to many deleterious effects for the physician, and far-reaching effects on their patients and hospital systems. The COVID-19 pandemic has presented new challenges that have further exacerbated the risk of burnout in anesthesiologists. It is critical to develop effective strategies to promote well-being and decrease burnout for physicians in this specialty. The purpose of this observational study was to evaluate the impact of a Physician Well-Being Initiative on distress and well-being in anesthesiologists. It was hypothesized that the wellness intervention would promote an improvement in well-being scores. Methods: The Physician Well-Being Initiative was launched in August 2019 in the Department of Anesthesiology, Pain Management and Perioperative Medicine at Henry Ford Hospital in Detroit, Michigan. The Physician Well-Being Initiative was designed to address several of the key factors that improve physician wellness, including 1) a sense of autonomy; 2) positive view of leadership; and 3) flexible schedule opportunities. To assess the impact of the Physician Well-Being Initiative on the well-being and distress scores of participating anesthesiologists, the physicians were emailed the validated Well-Being Index survey at baseline and 3, 6 and 12 months. The Well-Being Index evaluates multiple items of distress in the healthcare setting. The sample size was limited to the 54 anesthesiologists at Henry Ford Hospital. Results: Forty-four of the 54 anesthesiologists completed the baseline questionnaire. A total of 44 physicians answered the questionnaire at baseline, with more male than female physicians (35 males and 7 females) and the majority (17/44) in practice for 5-10 years. Thirty-two physicians completed the survey at 3 and 6 months, and 31 physicians at 12 months after the launch of the Physician Well-Being Initiative. Twenty-one physicians completed the questionnaire at all 4 time points. Although the COVID-19 pandemic started shortly after the 6-month surveys were submitted, results indicated that there was a 0.05 decrease in the Well-Being Index sum score for every 1-month of time (coefficient -0.05, 95% CI -0.01, -0.08, P = 0.013). This study shows that, with the wellness initiative in place, the department was able to maintain and potentially even reduce physician distress despite the concurrent onset of the pandemic. Conclusions: Following the launch of a sustained wellness initiative, this study demonstrates that physician wellness improved with time. This suggests that it takes time for a wellness initiative to have an effect on well-being and distress in anesthesiologists

Buprenorphine versus dihydrocodeine for opiate detoxification in primary care: a randomised controlled trial

Background Many drug users present to primary care requesting detoxification from illicit opiates. There are a number of detoxification agents but no recommended drug of choice. The purpose of this study is to compare buprenorphine with dihydrocodeine for detoxification from illicit opiates in primary care. Methods Open label randomised controlled trial in NHS Primary Care (General Practices), Leeds, UK. Sixty consenting adults using illicit opiates received either daily sublingual buprenorphine or daily oral dihydrocodeine. Reducing regimens for both interventions were at the discretion of prescribing doctor within a standard regimen of not more than 15 days. Primary outcome was abstinence from illicit opiates at final prescription as indicated by a urine sample. Secondary outcomes during detoxification period and at three and six months post detoxification were recorded. Results Only 23% completed the prescribed course of detoxification medication and gave a urine sample on collection of their final prescription. Risk of non-completion of detoxification was reduced if allocated buprenorphine (68% vs 88%, RR 0.58 CI 0.35–0.96, p = 0.065). A higher proportion of people allocated to buprenorphine provided a clean urine sample compared with those who received dihydrocodeine (21% vs 3%, RR 2.06 CI 1.33–3.21, p = 0.028). People allocated to buprenorphine had fewer visits to professional carers during detoxification and more were abstinent at three months (10 vs 4, RR 1.55 CI 0.96–2.52) and six months post detoxification (7 vs 3, RR 1.45 CI 0.84–2.49). Conclusion Informative randomised trials evaluating routine care within the primary care setting are possible amongst drug using populations. This small study generates unique data on commonly used treatment regimens