News & Publications

Automated preclinical detection of mechanical pain hypersensitivity and analgesia

The lack of sensitive and robust behavioral assessments of pain in preclinical models has been a major limitation for both pain research and the development of novel analgesics. Here we demonstrate a novel data acquisition and analysis platform that provides automated, quantitative, and objective measures of naturalistic rodent behavior in an observer-independent and unbiased fashion. The technology records freely-behaving mice, in the dark, over extended periods for continuous acquisition of two parallel video data streams: 1) near-infrared frustrated total internal reflection (FTIR) for detecting the degree, force and timing of surface contact, and 2) simultaneous ongoing video-graphing of whole-body pose. Using machine vision and machine learning we automatically extract and quantify behavioral features from these data to reveal moment-by-moment changes that capture the internal pain state of rodents in multiple pain models. We show that these voluntary pain-related behaviors are reversible by analgesics and that analgesia can be automatically and objectively differentiated from sedation. Finally, we used this approach to generate a paw luminance ratio measure that is sensitive in capturing dynamic mechanical hypersensitivity over a period of time and scalable for high-throughput pre-clinical analgesic efficacy assessment.

Source: Pain . 2022 May 11;(0). doi: 10.1097/j.pain.0000000000002680. Online ahead of p…

Social isolation modulates appetite and avoidance behavior via a common oxytocinergic circuit in larval zebrafish

Animal brains have evolved to encode social stimuli and transform these representations into advantageous behavioral responses. The commonalities and differences of these representations across species are not well-understood. Here, we show that social isolation activates an oxytocinergic (OXT), nociceptive circuit in the larval zebrafish hypothalamus and that chemical cues released from conspecific animals are potent modulators of this circuit's activity. We delineate an olfactory to subpallial pathway that transmits chemical social cues to OXT circuitry, where they are transformed into diverse outputs simultaneously regulating avoidance and feeding behaviors. Our data allow us to propose a model through which social stimuli are integrated within a fundamental neural circuit to mediate diverse adaptive behaviours.

Nat Commun 2022 May 11;13(1):2573.  doi: 10.1038/s41467-022-29765-9.

Source: Nat Commun . 2022 May 11;13(1):2573. doi: 10.1038/s41467-022-29765-9.

Yun Zhang on the state of forgetting

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Neuronal activity drives pathway-specific depolarization of peripheral astrocyte processes

Astrocytes are glial cells that interact with neuronal synapses via their distal processes, where they remove glutamate and potassium (K+) from the extracellular space following neuronal activity. Astrocyte clearance of both glutamate and K+ is voltage dependent, but astrocyte membrane potential (Vm) is thought to be largely invariant. As a result, these voltage dependencies have not been considered relevant to astrocyte function. Using genetically encoded voltage indicators to enable the measurement of Vm at peripheral astrocyte processes (PAPs) in mice, we report large, rapid, focal and pathway-specific depolarizations in PAPs during neuronal activity. These activity-dependent astrocyte depolarizations are driven by action potential-mediated presynaptic K+ efflux and electrogenic glutamate transporters. We find that PAP depolarization inhibits astrocyte glutamate clearance during neuronal activity, enhancing neuronal activation by glutamate. This represents a novel class of subcellular astrocyte membrane dynamics and a new form of astrocyte-neuron interaction.

Source: Nat Neurosci . 2022 Apr 28. doi: 10.1038/s41593-022-01049-x. Online ahead of pr…

Face neurons encode nonsemantic features

Significance Face neurons, which fire more strongly in response to images of faces than to other objects, are a paradigmatic example of object selectivity in the visual cortex. We asked whether such neurons represent the semantic concept of faces or, rather, visual features that are present in faces but do not necessarily count as a face. We created synthetic stimuli that strongly activated face neurons and showed that these stimuli were perceived as clearly distinct from real faces. At the same time, these synthetic stimuli were slightly more often associated with faces than other objects were. These results suggest that so-called face neurons do not represent a semantic category but, rather, represent visual features that correlate with faces.

Alexandra Bardon, Will XiaoCarlos R PonceMargaret S LivingstoneGabriel Kreiman 

 

Source: Proc Natl Acad Sci U S A . 2022 Apr 19;119(16):e2118705119. doi: 10.1073/pnas.2…

Multi-animal pose estimation, identification and tracking with DeepLabCut

Estimating the pose of multiple animals is a challenging computer vision problem: frequent interactions cause occlusions and complicate the association of detected keypoints to the correct individuals, as well as having highly similar looking animals that interact more closely than in typical multi-human scenarios. To take up this challenge, we build on DeepLabCut, an open-source pose estimation toolbox, and provide high-performance animal assembly and tracking-features required for multi-animal scenarios. Furthermore, we integrate the ability to predict an animal's identity to assist tracking (in case of occlusions). We illustrate the power of this framework with four datasets varying in complexity, which we release to serve as a benchmark for future algorithm development.

 

Jessy LauerMu ZhouShaokai YeWilliam Menegas, Steffen Schneider, Tanmay NathMohammed Mostafizur Rahman, Valentina Di SantoDaniel SoberanesGuoping FengVenkatesh N MurthyGeorge LauderCatherine DulacMackenzie Weygandt MathisAlexander Mathis

Source: Nat Methods . 2022 Apr;19(4):496-504. doi: 10.1038/s41592-022-01443-0. Epub 202…

Face neurons encode nonsemantic features

Significance Face neurons, which fire more strongly in response to images of faces than to other objects, are a paradigmatic example of object selectivity in the visual cortex. We asked whether such neurons represent the semantic concept of faces or, rather, visual features that are present in faces but do not necessarily count as a face. We created synthetic stimuli that strongly activated face neurons and showed that these stimuli were perceived as clearly distinct from real faces. At the same time, these synthetic stimuli were slightly more often associated with faces than other objects were. These results suggest that so-called face neurons do not represent a semantic category but, rather, represent visual features that correlate with faces.

Source: Proc Natl Acad Sci U S A . 2022 Apr 19;119(16):e2118705119. doi: 10.1073/pnas.2…

Remembering a Virtual Museum Tour: Viewing Time, Memory Reactivation, and Memory Distortion

A variety of evidence demonstrates that memory is a reconstructive process prone to errors and distortions. However, the complex relationship between memory encoding, strength of memory reactivation, and the likelihood of reporting true or false memories has yet to be ascertained. We address this issue in a setting that mimics a real-life experience: We asked participants to take a virtual museum tour in which they freely explored artworks included in the exhibit, while we measured the participants' spontaneous viewing time of each explored artwork. In a following memory reactivation phase, participants were presented again with explored artworks (reactivated targets), followed by novel artworks not belonging to the same exhibit (activated lures). For each of these objects, participants provided a reliving rating that indexed the strength of memory reactivation. In the final memory recognition phase, participants underwent an old/new memory task, involving reactivated vs. baseline (i.e., non-reactivated) targets, and activated and baseline lures. The results showed that those targets that were spontaneously viewed for a longer amount of time were more frequently correctly recognized. This pattern was particularly true for reactivated targets associated with greater memory strength (a higher reliving rating). Paradoxically, however, lures that were presented after targets associated with higher reliving ratings in the reactivation phase were more often erroneously recognized as artworks encountered during the tour. This latter finding indicates that memory intrusions, irrespective of the viewing time, are more likely to take place and be incorporated into true memories when the strength of target memory is higher.

Source: Front Psychol . 2022 Apr 14;13:869336. doi: 10.3389/fpsyg.2022.869336. eCollect…

The influence of shifting perspective on episodic and semantic details during autobiographical memory recall.

Shifting to a novel visual perspective during retrieval influences autobiographical memories (AM) and can lead to persistent changes in memories. Adopting an observer-like compared to an own eyes perspective reduces episodic information during AM recall, but less is known regarding how viewpoint influences semantic information. In the current study, we investigated how shifting from an own eyes to an observer-like perspective during narrative recall of AMs influences episodic and semantic information. Shifting perspective reduced the number of episodic details associated with emotions and thoughts, and also led to similar reductions in personal semantics. We replicated prior research showing that shifting perspective reduces emotional intensity in subsequent memories, but these subjective changes were not coupled with objective changes in a narrative recall. Our findings suggest that shifting perspective influences the interplay between episodic and semantic information during proximate recall and subjective changes when memories are later recalled.

 

Chloe I KingAnna S L RomeroDaniel L SchacterPeggy L St Jacques 

Source: Memory . 2022 Apr 7;1-13. doi: 10.1080/09658211.2022.2061003