News & Views in 2018

Alzheimer’s disease (AD) research is hampered by a lack of models that recapitulate all key disease features. Park et al. introduce a microfluidic device containing a 3D culture of human neurons, astrocytes, and microglia that develop AD-like pathology, revealing a potentially important inflammatory mechanism of neurodegeneration.

Often overlooked, the paraventricular nucleus of the thalamus is a stress-sensitive region in the midline thalamus essential for stress-induced adaptations. Using cutting edge in vivo monitoring approaches, Beas, Wright et al. identify a circuit by which stress disinhibits the midline thalamus through dopaminergic modulation arising from the locus coeruleus.

The origin of microglia, the resident macrophage population of the CNS, has been a long-standing matter of debate. Here we discuss two seminal studies published in 2007 in Nature Neuroscience that significantly contributed to a better understanding of microglia ontogeny and homeostasis in the adult brain.

New techniques enable simultaneous optogenetic stimulation and calcium imaging from ensembles of tens of neurons in vivo. Improved opsins are localized to the cell body, minimizing spurious activation of the optically unresolvable neuropil. Two-photon light pulses are sculpted in space, time, and wavelength to efficiently target the desired cells.

In 2004, Weaver et al. published evidence in Nature Neuroscience for the lasting epigenetic impact of maternal care within the hippocampus of rat offspring. This conceptual and methodological leap contributed to the evolution of environmental and behavioral epigenetics and continues to inspire challenging questions about genes, environments, and their legacy.

Synaptic connections adapt homeostatically to changes in experience to maintain optimal circuit function. A study demonstrates that different forms of synaptic homeostasis respond to distinct aspects of circuit activity, suggesting that neurons can gauge and adapt to the both the quality and quantity of circuit activity.

Recurring bursts of thalamocortical cells were thought to be indispensable in driving absence seizures. A new study demonstrates that bursts from inhibitory thalamic reticular neurons are crucial instead. Reticular bursts are driven by cortical inputs and govern precise timing of thalamocortical cell activity during seizures.

The behavioral state of a human or animal can dramatically alter how information is processed in its neural circuits. Albergaria et al. show that locomotion enhances the performance of a cerebellum-dependent behavior. The results provide new constraints on how information is represented there to support learning.

Epidemiology and animal research have shown that the offspring of mothers who experience inflammation during pregnancy are at increased risk for psychopathology. A human study links a mother’s inflammation during pregnancy to her newborn’s functional brain organization and the child’s working memory two years later.

When making decisions, new information sometimes calls for a change of mind. New results indicate that regions of the prefrontal cortex play distinct roles in evaluating new evidence in light of a previous choice and translating the result of this evaluation process into an explicit report of one’s subjective confidence.

The dogma that self-renewal is a defining characteristic of stem cells, which stemmed from studies of the hematopoietic hierarchy and quickly spread by analogy to all tissues, has been shattered by scientists pointing a microscope at the hematopoietic system itself. A microglial cell is clearly fully differentiated, and yet it self-renews.

Spinal cord injury disrupts connectivity between the brain and the body. With electrochemical neuromodulation and intensive rehabilitation training, the cortex can functionally connect with spinal circuits below injury by relaying signals through the brainstem.

A key component of learning involves updating existing motor plans in response to altered sensory feedback. By using a brain–computer interface, Golub et al. show how such learning changes the activity of neural populations in primary motor cortex—and how it does not.

The human brain shows regional selective vulnerability to the pathology of Alzheimer’s disease. Jacobs et al. show that the protein amyloid-β promotes the spread of tau through specific components of a neural system underlying memory formation, thus leading to the prominent early symptom of amnesia.

Humans and animals can react to the affective state of others in distress. However, exposure to a stressed partner can trigger stress-related adaptations. Two studies shed light on the mechanisms underlying the behavioral responses toward stressed individuals and on the synaptic changes associated with social transmission of stress.

Direct conversion of adult Huntington’s disease patient fibroblasts into medium spiny neurons recapitulates hallmark phenotypes such as cell death, in contrast to models that lack epigenetic markers of aging. This successful ‘disease-in-a-dish’ highlights the benefits of capturing age in an adult-onset disorder model.

Using a series of functional manipulation and in vivo recording tools, Park et al. identify a pathway from medial preoptic CaMKIIα-expressing neurons to the ventral periaqueductal gray that mediates object craving and prey hunting.

Neuroimaging studies of human entorhinal cortex activity revealed 60-degree spatial periodicity, a hallmark of grid cells, as gaze movements were made throughout the visual field. This activity may serve as a framework for organizing visuospatial memory.

An extensive single-cell transcriptomic collection of over 30,000 cells of the developing hippocampus shows that adult hippocampal neurogenesis follows the same differentiation path as embryonic neurogenesis, but the cell of origin differs. This work provides an invaluable resource with important implications for neuronal regeneration.

Compromised compartmentalization of nucleus and cytoplasm has emerged as a central feature of aging and neurodegenerative diseases. Nucleocytoplasmic transport is disrupted, with widespread mislocalization of nuclear pore proteins, in TDP-43 proteinopathies such as, amyotrophic lateral sclerosis and frontotemporal dementia.