Reviews & Analysis

A newly recognized process in neurodegenerative disease is accumulation of misfolded protein aggregates that self-replicate to spread damage between cells and tissues. This process has implications in designing strategies for treatment and diagnosis.

Adequate blood supply and vascular integrity are key to normal brain functioning. Cerebral blood flow and blood–brain barrier disruption contribute to Alzheimer’s disease and other neurodegenerative disorders as reviewed in humans and animal models.

How we value our own rewards depends on what others have. A new study shows that neurons in the medial prefrontal cortex selectively monitor the value of rewards received by oneself or by another individual, whereas midbrain dopaminergic neurons integrate these values to generate social subjective reward values.

The surge in single-cell and single-nucleus RNA-sequencing has raised the question of the value of bulk tissue transcriptomics. Kelley et al. describe an analysis framework by which existing bulk transcriptomic data can be reanalyzed using cell-type-specific data to yield insights into cell-type variation across brain regions and diseases.

Twenty years ago, 2 studies showed that behavioral experience affects proliferation & survival of newborn neurons in adult hippocampus, suggesting adult neurogenesis as a form of experience-dependent neuroplasticity relevant to memory, emotion, & mental health.

A study has found that young male mice with a mutation of the autism-associated gene Chd8 show abnormal behaviors and elevated neuronal activation in several brain areas under stressful conditions, while female mice with the same mutation have reduced baseline neuronal activity, which may protect them from developing these abnormal phenotypes.

A deep-learning-based software package called DeepLabCut rapidly and easily enables video-based motion tracking in any animal species. Such tracking technology is bound to revolutionize movement science and behavioral tracking in the laboratory and is also poised to find many applications in the real world.

The authors review recent work at the intersection of cognitive science, computational neuroscience and artificial intelligence that develops and tests computational models mimicking neural and cognitive function during a wide range of tasks.

Heterogeneity of function in microglia from different brain regions is suspected but largely unknown. This paper identifies the epigenetic mechanism underlying differential phagocytic activity of microglia in discrete brain regions and examines the consequences of inducing an appetite not commensurate with the level of cell death in the region in which they reside.

In the 20th century we thought the brain extracted knowledge from sensations. The 21st century witnessed a ‘strange inversion’, in which the brain became an organ of inference, actively constructing explanations for what’s going on ‘out there’, beyond its sensory epithelia. One paper played a key role in this paradigm shift.

Phenotypic diversity confers the benefits of adaptation to an evolving species. Random perturbations in our genetic structure may result in new functions required for some change in our environment, and we can survive outside of our happy niche for generations. But where are the limits on this sort of diversity?

Protein kinases are key regulators of excitatory synapse plasticity. In this issue, using novel optical reporters of protein kinase C (PKC) activity, Colgan et al. identify PKCα as critical for integrating NMDA receptor and neurotrophin signaling to control dendritic spine structural plasticity, synaptic potentiation, and learning and memory.

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.

This article presents best practices on how field potential recordings (EEG, MEG, ECoG and LFP) can be analyzed to identify large-scale brain dynamics, and highlights issues and limitations of interpretation.

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.

In this Perspective, Josh Berke discusses recent developments in the study of dopamine function. He proposes a model that explains how dopamine can serve as both a learning signal and as a critical modulator of motivated decision-making.