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Dopamine neurons in the ventral tegmental area are thought to signal reward prediction error. The authors show that these neurons respond with striking homogeneity during classical conditioning. All dopamine neurons appear to calculate reward prediction error similarly, enabling robust and consistent broadcasting of this signal throughout the brain.
The authors defined a roadmap for investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders. Their proof-of-concept study using the largest available common variant data sets for schizophrenia and volumes of several (mainly subcortical) brain structures did not find evidence of genetic overlap.
Recurrent, reciprocal genomic disorders due to non-allelic homologous recombination (NAHR) are a major cause of human disease. The authors developed a CRISPR/Cas9 genome engineering method that directly targets segmental duplications and efficiently mimics the NAHR-mediated mechanism of microdeletion and microduplication that occurs in vivo using 16p11.2 and 15q13.3 as proof-of-principle models.
Unlike artificial sweeteners, sugar promotes ingestive behavior via both gustatory and post-ingestive pathways. Tellez et al. find that separate basal ganglia circuits mediate the hedonic and nutritional actions of sugar. They demonstrate that sugar recruits a dedicated striatofugal pathway that acts to prioritize calorie-seeking over taste quality.
This study shows that learning-induced plasticity of local parvalbumin (PV) basket cells is specifically required for long-term, but not short to intermediate-term, memory consolidation in mice. PV plasticity depends on local D1/5 dopamine receptor signaling 12–14 h after acquisition for its continuance, ensuring enhanced sharp-wave ripple densities and memory consolidation.
Gene-regulatory elements are drivers of evolutionary divergence, yet where these are located and which are evolutionarily relevant is unclear. In this work, large-scale epigenomic analysis of human, rhesus and chimpanzee brain tissue allowed the identification of human-specific gene-regulatory changes that contributed to the emergence of the human brain.
Heterogeneity within distinct cell populations resident in the central nervous system is increasingly recognized as important for functional diversity, plasticity and sensitivity to neurological disease. The authors demonstrate genome-wide diversity of microglia dependent on brain localization in the young adult and show that aging of microglia occurs in a regionally variable manner.
Wallach et al. use closed-loop artificial whisking in anesthetized rats to show that vibrissal mechanoreceptors extract phase information from on-going whisker kinematics in a frequency- and amplitude-invariant manner. Brainstem paralemniscal neurons preserve this phase information while filtering out information about whisker offset; lemniscal neurons preserve both types of information.
The role of subcortical acetylcholine in decision-making under uncertainty is ill-defined. By combining genetic tools, computational modeling and a new multi-armed bandit task for mice, the authors show that nicotinic acetylcholine receptors expressed in the ventral tegmental area drive the motivation to seek reward uncertainty.
In this study, the authors show that PTEN alters synaptic function after PDZ-dependent recruitment into spines induced by amyloid-β. This mechanism is crucial for pathogenesis, as preventing PTEN-PDZ interactions renders neurons resistant to amyloid-β and rescues cognitive function in Alzheimer's disease models. This suggests that PTEN is a critical effector of the synaptic pathology associated with Alzheimer's disease.
Adult-born neurons are already contributing to learning and memory at immature developmental stages. Heigele et al. show that during the first 3 weeks after mitosis, the young cells fire action potentials generated by excitatory GABAergic synapses. Strong GABAergic synaptic activity, however, inhibits spiking, thereby generating a well-defined GABAergic excitation window.
Natural killer (NK) cells are retained and reside in the vicinity of neural stem cells (NSCs) in the brain subventricular zone during the chronic phase of multiple sclerosis in humans and its animal model in mice. In this study, the authors show that these NK cells limit NSCs' reparative capacity following brain inflammation, while NSCs promote NK survival via an interleukin-15-dependent mechanism.
The authors find that Kif1a has sequential roles during cortical development. Kif1a inhibition blocks basal nuclear migration in radial glial progenitor cells, resulting in a persistent proliferative state. Kif1a inhibition subsequently disrupts neuronal migration at the multipolar-to-bipolar transition, with a massive non-cell-autonomous arrest of surrounding neurons. These effects are phenocopied by Dcx RNAi and rescued by BDNF, a Kif1a cargo protein.
The serotonergic raphe nuclei modulate neuronal function typically over minutes or hours. The authors report that raphe nuclei affect odor responses in output neurons of the olfactory bulb at sub-second time scales. These effects are mediated through multiple neurotransmitters and are distinct depending on the type of output neuron.
The authors propose that deciding where to look and reach depends on how neurons in the posterior parietal cortex communicate with each other. They find that ‘dual-coherent’ neurons, which tend to fire spikes timed to neural activity within and across the banks of the intraparietal sulcus, predict look-reach choices before neurons without this property.
Several prominent theories propose that, in situations affording more than one possible action, the brain prepares, in parallel, multiple competing movements before selecting one. The authors provide evidence for this idea, showing that individuals simultaneously specify distinct feedback gains, a critical component of control, for competing target options.
Animals can fear specific objects with no previous experience. For example, naive mice are innately afraid of cats. Here the authors employed optogenetics and behavioral assays to determine the neural circuit mechanisms involved in mediating olfactory cue–induced innate fear in mice.
Mammalian cortex comprises a variety of cells, but the extent of this cellular diversity is unknown. The authors defined cell types in the primary visual cortex of adult mice using single-cell transcriptomics. This revealed 49 cell types, including 23 GABAergic, 19 glutamatergic and 7 non-neuronal types.
