Brief Communications

Prefrontal–hippocampal communication has been implicated in memory, but the temporal dynamics of information flow are not fully understood. In this study, the authors demonstrate that information flows between hippocampus and prefrontal cortex in different directions depending on the behavioral phase of a spatial-context-guided object discrimination task.

The authors analyzed the exome sequences of 2,104 intellectual disability patients and their parents. They identified 10 novel candidate genes associated with specific clinical phenotypes.

Safaiyan et al. demonstrate that myelin fragments progressively pinch off from aged myelin sheaths and are taken up and cleared by microglia. Age-associated myelin breakdown is substantial and saturates the degradative capacities of microglia, leading to lysosomal storage and an immune activation in microglia with time.

Feeding is controlled by hedonic cues that may override the homeostatic needs to eat, causing obesity. Labouèbe et al. have identified hypoglycemia-activated neurons in the paraventricular thalamus that increase motivated sucrose-seeking behavior. As their activity is not suppressed by fructose or sweeteners, these cells may contribute to sugar overconsumption and diabetes.

Hedonic value is a dominant aspect of olfactory perception. The authors combine immediate early gene mapping and optogenetics to show that the degree of behavioral attraction to odors is represented along the antero-posterior axis of the ventral olfactory bulb. This suggests that organization of the olfactory bulb reflects hedonic value.

By combining neuroimaging with an implicit behavioral measure (mouse-tracking), the authors demonstrate that stereotypes can alter the brain's visual representation of a face's gender, race, and emotion. Perceptions of social categories were biased by a subject's stereotypical associations, and this bias correlated with neural representations of those categories.

In this study the authors have imaged the growth of adult-born dentate granule cell dendrites in vivo longitudinally over several weeks. They have found that branch addition is dependent on behavioral experience and molecular cues and that pruning acts homeostatically to promote a similar dendritic structure for all granule cells.

Theories propose hippocampal memories are consolidated to the cortex during reactivation events known as replay. However, the involvement of the medial entorhinal cortex (MEC) in consolidation remains poorly understood. Ólafsdóttir et al. demonstrate coordinated replay between the hippocampus and MEC, with hippocampus leading, suggesting hippocampal memories are broadcast to MEC.

The authors document a novel neurogenic mechanism to explain the clinical syndrome known as spinal cord injury–induced immune deficiency. Specifically, they show that new spinal–splenic sympathetic circuitry forms below the level of injury, creating an exaggerated sympathetic anti-inflammatory reflex. Inhibiting excitatory interneurons within this circuitry blocks immune suppression.

Expectations about what will appear next guide perception. Using high-resolution fMRI and multivariate pattern analysis, the authors find that such predictive coding in early visual cortex could arise from pattern completion in hippocampal subfields. They show that these two processes are related and explore their behavioral significance and relative timing.

Optogenetic inhibition of specific axonal projections is a potentially powerful technique for assessing defined neural pathways’ contributions to behavior. The authors report that while optogenetic inhibition can efficiently attenuate presynaptic release, it can under some conditions lead to undesired effects such as depolarization and increased spontaneous release.

Pathogenesis for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) remains largely unknown. Using a mouse model of ALS and FTD, the authors found that somatostatin interneurons in motor cortex were hyperactive. This hyperactivity led to the disinhibition of pyramidal neurons and correlated with signs of excitotoxicity. Ablating somatostatin interneurons restored the excitability of pyramidal cells to a normal level and prevented neurodegeneration.

Subsets of hippocampal neurons store map-like representations of experienced environments. The authors optogenetically silenced a neuronal population active in an environment and saw an alternative map emerge. In a cocaine-paired environment, this approach neutralized drug-place preference, implicating recoding of spatial memory engrams as strategy for alleviating maladaptive behaviors.

Dopaminergic neurons in the ventral tegmental area (VTA) contribute to mediating stress susceptibility and resilience. The authors demonstrate that noradrenergic neurons in the locus coeruleus can drive the activity of these dopaminergic VTA neurons to generate a resilient response to chronic stress.

Increases in synaptic inhibition have been proposed to underlie divisive normalization in distal neural networks. Here, using optogenetic stimulation and intracellular recordings in mouse visual cortex, the authors argue that normalization is a result of a decrease in synaptic excitation.

Neuropathic pain poses a major healthcare burden. The authors show that a specific set of neurons in the nucleus accumbens, a region long associated with affect, were changed in a mouse model of neuropathic pain. A pharmacotherapy that is well tolerated in man reversed these adaptations and alleviated pain.

The authors used a reversible inactivation technique that has not been used before in Old World monkeys, inhibitory chemogenetic receptors (DREADDs), to demonstrate that disconnecting a large region of monkey prefrontal cortex (orbitofrontal cortex) from a region in the temporal lobe (rhinal cortex) reduces sensitivity to differences in reward size.

Mesolimbic dopamine has been implicated both in reward prediction and in promoting movement. This study demonstrates that the patterns of dopamine release in the nucleus accumbens core are shaped by the initiation of appropriate reward-guided actions and prospective response accuracy, and not just prediction errors.

Immunotherapy with antibodies targeting the amyloid-β peptide has yet to show any cognitive benefit in Alzheimer's disease patients in clinical trials. In vivo two-photon imaging in mouse models of Alzheimer's disease now reveals that these antibodies do not alleviate neuronal dysfunction and can even worsen it.

Endogenous neural stem cells in the adult hippocampus are generally considered to be bi-potent. The authors show in mouse that inactivation of neurofibromin 1 (Nf1), a gene that is mutated in neurofibromatosis type 1, unlocks a latent oligodendrocyte lineage potential of neural stem cells to produce all three lineages in vivo.