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Yang et al. demonstrate that sensory neurons are enriched for the anthrax toxin receptor-2. Edema toxin, which acts via this receptor, induces analgesia in mice and can also be engineered to deliver large cargoes such as botulinum toxin in order to selectively silence sensory neurons.
Discovering that nociceptive sensory neurons express the receptor for anthrax toxin, Yang et al. show that anthrax toxin can induce potent analgesia in mice and facilitate the delivery of potentially analgesic cargo proteins into nociceptive neurons.
Allen et al. introduce the Natural Scenes Dataset — high-resolution fMRI data from eight individuals scanned as they collectively viewed more than 70,000 natural images and performed a continuous recognition task. This resource promises to yield insights into visual perception and memory and to help bridge cognitive neuroscience and artificial intelligence.
The authors measured high-resolution fMRI activity from eight individuals who saw and memorized thousands of annotated natural images over 1 year. This massive dataset enables new paths of inquiry in cognitive neuroscience and artificial intelligence.
Using mouse models of TDP-43 neurodegeneration, this study demonstrates that microglial TREM2 binds TDP-43 and thus mediates its phagocytic clearance. TDP-43 may serve as a possible ligand for microglial TREM2 in TDP-43-related neurodegeneration.
Our brains are wired to steer us toward novel experiences. Ogasawara et al. define nodes in a network that underlies novelty-seeking behavior distinct from novelty-orienting responses. In this network, anterior ventral medial temporal cortex (AVMTC) mediates novelty-related sensory processing, and zona incerta uses input from AVMTC to guide gaze shifts for novelty seeking.
Primates seek opportunities to view novel objects even when these objects have no extrinsic reward value. Ogasawara et al. show that this novelty seeking is regulated by a temporal cortex→zona incerta pathway, rather than by dopamine neurons.
The structural basis for the clinical and side effects of antipsychotic drugs has not been resolved. A new study combined X-ray crystallography with medicinal chemistry and behavioral pharmacology to design a new dopamine D2 receptor partial agonist that, in mice, shows not only antipsychotic-like activity but also 5-HT1A-receptor-dependent antidepressant-like effects.
The authors developed AAV capsids for robust transgene expression in the brain with decreased liver targeting after non-invasive administration in mice and marmosets, enabling more targeted systemic gene delivery to the brain.
By solving the complex structures of third-generation antipsychotic drugs (TGAs) with the 5HT2A receptor, Chen et al. unravel their unique pharmacology and design a novel TGA lead that has cognition-improving and potential antidepressant properties.
What you hear influences what you see. The authors show that experience with an audio-visual stimulus reshapes the input from auditory cortex to visual cortex, suppressing predictable visual input to amplify the unpredictable.
In this study, the authors show that VTA DA neurons display heterogeneous responses during interactions with an unfamiliar conspecific. The activity of DA neurons encodes social prediction error and drives social reinforcement learning.
As 2021 winds down, we reflect on how our field has progressed with regard to diversity, equity, and inclusion since 2020, and how far we still have to go.