Neuroscience

eLife Assessment

This important study provides the first in vivo evidence that nonsense-mediated mRNA decay (NMD) in mature astrocytes regulates astrocyte function, synaptic plasticity, and anxiety-related behavior. Using a broad range of approaches, the authors show that conditional deletion of Upf2 alters astrocyte morphology and calcium signaling while impairing synaptic transmission and plasticity, providing solid support for the central conclusion that astrocytic NMD influences neural circuit function. Some key mechanistic claims remain incompletely supported, including whether phenotypes reflect astrocyte remodeling versus loss, the interpretation of synaptic engulfment data, the link between NMD targets and calcium signaling, and the extent to which calcium dysregulation explains the observed synaptic and behavioral effects.

eLife Assessment

This important submission from Ambler and colleagues brings new insights into how torpor conditions may confer resilience in cases of cardioprotection. It has novelty, which can be enhanced by additional in vivo support. The study is backed by solid evidence, and represents a unique interoceptive mechanism of interest.

eLife Assessment

This useful study investigates noise-robust and energy-efficient circuit mechanisms for working memory by optimizing connectivity and reports that the resulting networks exhibit rotational dynamics and better match aspects of PFC population recording. However, the supporting evidence remains incomplete, given the restricted linear, task-specific training and analysis, and limited comparisons with other prominent models. The manuscript would be strengthened by extending the analysis to nonlinear dynamics, providing more rigorous comparisons with alternative models, and establishing a stronger link to prior theoretical and experimental work.

eLife Assessment

This paper reports the findings of a neuroimaging experiment that tested the hypothesis that the cortex, specifically early visual areas, reinstates certain content from past episodic events. This is a useful study that highlights the role of early sensory cortices in supporting rapid, one-shot learning of location information for long-term memory. The strength of the evidence is solid, with the methods, data, and analyses broadly supporting the claims.

eLife Assessment

This important study shows that long-range somatostatin-expressing neurons in the ventrolateral periaqueductal grey that project to the rostral ventromedial medulla selectively suppress pain responses during conditioned fear. The evidence supporting these conclusions is exceptional, with methods spanning a novel cued fear-conditioned analgesia paradigm, cell-type-specific optogenetic activation and inhibition, anatomical circuit tracing, and in vivo spinal cord electrophysiology. These results will be of broad interest to systems and behavioral neuroscientists studying fear, pain, and descending pain-control circuitry.