Volume 25 Issue 2, February 2022

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.

Adult male rodents have long been known to show stronger hippocampal long-term potentiation (LTP) and learning than females. Le et al. find that this sex difference is reversed in pre-pubescent animals, and identify a female-specific mechanism that increases LTP threshold and decreases spatial memory in females after puberty.

The duodenum distinguishes between sugar and sweeteners, but the cells involved in this process remain elusive. Buchanan and colleagues engineered a flexible optic fiber for optogenetic manipulation of gut cells in mice. Silencing duodenal CCK cells reduced the preference for sugar over sweetener intake. Gut optogenetics may elucidate how the gut–brain axis regulates feeding and glucose homeostasis.

Complex and intelligent behavior depends not just on sensory evidence but also on internal cognitive state. Ashwood et al. use a powerful statistical method to identify hidden internal states in choice data.

Roy, Zhang et al. discuss how modern neuroscience is revealing underappreciated heterogeneity in thalamic cell types, which leads to the idea that ‘thalamic subnetworks’ provide a more appropriate level of functional description than thalamic nuclei.

By profiling multiple epigenetic layers and enhancer activity in vivo, the authors show a widespread remodeling of the regulatory landscape during mouse cortical development and identify Neurog2 as a key transcription factor driving this process.

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.

Le et al. show that, in rodents, females have lower spatial learning threshold before puberty and that sex differences in synaptic plasticity and learning thresholds reverse in the transition to adult life.

Buchanan, Rupprecht, Kaelberer and colleagues show that the preference for sugar over sweetener in mice depends on gut neuropod cells. Akin to other sensor cells, neuropod cells swiftly communicate the precise identity of stimuli to drive food choices.

The authors implement model-based analyses to uncover strategies used by mice and humans during sensory decision-making. Contrary to common wisdom, mice do not lapse and, instead, switch between sustained engaged and disengaged states.

The authors analyzed the levels of more than 8,600 proteins across more than 1,000 brain tissues to arrive at a consensus AD brain protein co-expression network that illustrates the complexity and multiple pathological processes that occur in AD, many of which are not reflected at the RNA level.

Answer ALS is a resource of patient-derived iPS cell lines, multi-omic data derived from iPS neurons and longitudinal clinical and smartphone data from over 1,000 patients with ALS. This serves as a foundation to identify distinct disease subgroups.

Using single-nuclei RNA sequencing to interrogate gene expression in peripheral nerves, Yim et al. reveal diverse glial subpopulations and identify a novel myelinating Schwann cell subtype that preferentially ensheathes motor axons and is depleted in ALS nerve samples from mouse models and patients.

Neuropixels probes were used to simultaneously record from more than 200 cortical neurons in human participants during neurosurgical procedures. The approach could reveal insights underlying human cognition and pathology.