Volume 24 Issue 6, June 2021

In neurodegenerative diseases, certain types of neurons perish first, but the mechanisms of this selective neuronal vulnerability remain unclear. A new study now highlights a crucial role for apolipoprotein E in driving neuronal death in both ageing and Alzheimer’s disease.

Hu et al. show that the posterodorsal medial amygdala selectively controls social-reward seeking through its intersection with canonical dopaminergic reward circuits. To identify this circuitry, the authors developed an elegant new affiliative social operant procedure that separates social interaction from social-reward seeking.

The act of remembering information or planning actions in short term memory can often be robust to distracting or conflicting information. Finkelstein et al. reveal the neural computations behind this robustness against distractors using a combination of optogenetics, behavior, neural recordings and neural network modelling.

Drawing from advances in mathematics and related fields, we show that biophysical models of large-scale neural dynamics can help to bridge the gap between neuromodulation at the cellular scale and mesoscale systems dynamics at the whole-brain level.

The authors find that calcium signaling triggers liquid–liquid phase separation of CaMKII. This reorganizes the postsynaptic structure, acting as a potential mechanism to increase the efficacy of synaptic transmission during memory formation.

Selective neurodegeneration is a critical causal factor in Alzheimer’s disease. Zalocusky et al. demonstrate a causal chain linking neuronal ApoE expression to MHC-I expression and, subsequently, to tau pathology and selective neurodegeneration.

Brain genetic co-expression networks pinpoint specific, convergent synaptic pathways—rather than the complement system—through which genetic variation at the C4 locus imparts risk for schizophrenia.

Wingo et al. integrate depression GWAS results with human brain proteomes to perform proteome-wide association studies followed by Mendelian randomization. They identify 25 proteins as potential causal mediators of depression, of which 20 are new.

Xu et al. developed and characterized a new animal model of maternal immune activation based on a parasite mimetic. They show that immune and behavioral abnormalities in adult offspring are reversed by adoptive transfer of regulatory T cells.

Social interactions and relationships are often associated with a rewarding experience. Hu et al. show that mice display positive reinforcement of social interaction, and they identify an amygdala-to-hypothalamus circuit in mediating this social reward.

The flow of information in the brain is regulated over space and time. The authors show that mice can adaptively filter stimuli originating in the sensory cortex. The stimuli are gated by attractor dynamics in the frontal cortex, revealing a mechanism of gating of neural information.

McNamee et al. develop a theory of entorhinal–hippocampal processing. Distributed entorhinal input drives hippocampal activity between distinct statistical and dynamical regimes of activity, thereby unifying several empirical observations.

Julian and Doeller show that trial-by-trial modulation of map-like representations in the human hippocampal–entorhinal system predicts contextual memory retrieval during virtual reality navigation independent of visual experience.

Sun et al. present BARseq2, a high-throughput method combining in situ sequencing of endogenous mRNAs with barcode-based axonal projection mapping, and apply it to identify cadherins that correlate with similar projections in two cortical areas.

Liu et al. present a flexible, insertable and transparent microelectrode (FITM) array termed Neuro-FITM. Multimodal recordings with Neuro-FITM reveal diverse and selective large-scale cortical activation patterns associated with hippocampal sharp-wave ripples.