Volume 22 Issue 5, May 2019

DNA damage or cellular stresses can induce senescence, and increased senescence with aging contributes to age-associated tissue damage, inflammation and disease. Zheng and colleagues report increased senescent oligodendrocyte progenitor cells around amyloid plaques. Therapeutically eliminating these senescent cells may influence the onset and progression of Alzheimer’s disease pathology.

The ventrolateral and medial orbitofrontal cortices are involved in selecting actions based on the value of expected outcomes. Malvaez and colleagues reveal that these brain regions are specialized in value encoding (ventrolateral orbitofrontal cortices) versus value memory retrieval (medial orbitofrontal cortices) and that they interact with the basolateral amygdala to orchestrate goal-oriented reward-seeking.

Noninvasive delivery of alternating electrical currents to temporal and prefrontal brain regions improves working memory and reverses age-related changes in brain dynamics in the elderly, report Reinhart and Nguyen in this issue of Nature Neuroscience. They also report a similar effect in young adults with poor working memory performance.

Robust conclusions require rigorous statistics. In 2009 a seminal paper described the dangers and prevalence of double-dipping in neuroscience. Ten years on, I consider progress toward statistical rigor in neuroimaging.

Wang et al. present a computational framework integrating multi-omics data to infer key schizophrenia risk genes from GWAS data. These genes are predominantly expressed in the developing brain and are enriched for targets of approved drugs.

Barak et al. show that deletion of Gtf2i, a gene deleted in Williams syndrome, from the excitatory neurons of the forebrain reduced myelin thickness and axonal conduction. Rescuing myelination with a US Food and Drug Administration-approved drug restored normal behavior.

The authors report aberrant oligodendrocyte precursor cell (OPC) interactions with blood vessels in certain multiple sclerosis lesions. These clustered OPCs can disrupt the blood–brain barrier and can impair OPC recruitment to repairing lesions.

The Alzheimer’s disease (AD) amyloid-beta peptide causes oligodendrocyte progenitor cells to undergo senescence, contributing to neuroinflammation and cognitive impairment. Treatment of AD mice with senolytic drugs ameliorates AD neuropathologies and cognitive deficits.

Using animal models and clinical samples, the authors report that glioblastoma metabolites activate the transcription factor aryl hydrocarbon receptor in tumor-associated macrophages to modulate their function and T cell immunity, promoting tumor growth.

The authors have identified a subpopulation of astrocytes that is enriched in cortical layer V of the mouse cortex and is also present in the human cortex. These cells express Norrin, a protein mutated in a rare neurological degenerative disease called Norrie disease. Norrin acts on neurons to modify their morphology and activity.

Lacagnina et al. show that extinction training suppresses the associated hippocampal fear engram and generates a distinct extinction engram. Reactivation of extinction engram cells reduces fear, while reactivation of fear engram cells causes fear relapse.

The value of an anticipated reward is crucial to adaptive decision-making. The authors delineate the neural circuitry supporting value encoding and retrieval, respectively, by lateral and medial orbitofrontal cortex projections to the basolateral amygdala.

Yoshida et al. show in mice that sustained engagement in motivated behavior requires suppression of ventral hippocampus activity through activation of median raphe serotonin neurons.

Clancy et al. investigated the relationship between individual neuron activity and cortex-wide dynamics. Neurons were diversely coupled to distal areas, and locomotion affected how neurons in different areas coupled with distal activity.

Sensory stimuli are recognized faster when they are expected. Comparing a spiking network model to cortical recordings from behaving animals, Mazzucato et al. show that expectation accelerates sensory processing by modulating the intrinsically generated activity preceding stimulation.

Fouragnan et al. used neuroimaging and ultrasound neuromodution in non-human primates to demonstrate the causal role of the anterior cingulate cortex in translating counterfactual values in future choices.

Mollink et al. establish a link between white matter microstructure and functional connectivity using MRI data from 11,354 individuals in the UK Biobank. GWAS identified genetic associations of these microstructure–function relationships.

The authors develop a noninvasive stimulation protocol to restore neural synchronization patterns and improve working memory in older humans, contributing to groundwork for future drug-free therapeutics targeting age-related cognitive decline.

A peroxidase-based labeling method allows simultaneous visualization of multiple cell types using electron microscopy without the need for spectral separation, enabling identification of synapses between genetically defined neuronal populations.