Volume 25 Issue 1, January 2022

Microglia form barriers that attenuate the propagation of amyloid pathology in Alzheimer’s disease. d’Errico et al. have uncovered a paradoxical ability of microglia to spread amyloid plaques, which depends on the transcription factor IRF8. Here, we highlight the contexts in which this may happen and discuss outstanding questions.

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-HT_1A-receptor-dependent antidepressant-like effects.

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.

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.

Neuroscientists can measure activity from more neurons than ever before, garnering new insights and posing challenges to traditional theoretical frameworks. New frameworks may help researchers use these observations to shed light on brain function.

This study shows that Aβ from transgenic host tissue is able to enter and deposit within wild-type grafts via microglia, thus identifying microglia as carriers of Aβ deposition into previously unaffected brain tissue.

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.

By solving the complex structures of third-generation antipsychotic drugs (TGAs) with the 5HT_2A receptor, Chen et al. unravel their unique pharmacology and design a novel TGA lead that has cognition-improving and potential antidepressant properties.

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 authors uncovered the physiological mechanism underlying the functional role of melanin-concentrating hormone in the dorsolateral septum, a region involved in routing hippocampal firing rhythms and encoding spatial memory.

Xie et al. report that GABAergic neurons in the anterior hypothalamic nucleus control mechanically evoked defensive attack, an important survival behavior that is often the last line of defense against threatening stimuli (for example, predators).

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.

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.

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.

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.