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Peixoto et al. show that Shank3B−/− mice exhibit premature development and subsequent arrest of striatal afferent connectivity. This phenotype is a result of cortical hyperactivity during a period that is marked by robust synaptogenesis and enhanced excitability of spiny projection neurons, and indicates that early imbalances in cortical activity disrupt normal corticostriatal maturation.
In this study, He et al. find that the CHARGE syndrome–related chromatin remodeler Chd7 regulates the initiation of myelination and remyelination in the CNS. Chd7 interacts with Sox10 to orchestrate the transcriptional state of myelinogenic genes and serves as a molecular nexus of the regulatory networks that contribute to white matter pathogenesis in CHARGE syndrome.
Using a combination of behavioral and physiological approaches, the authors show that ON and OFF motion detection pathways in Drosophila exhibit distinct temporal tuning properties. Computational modeling suggests that these asymmetric tuning properties improve the fly's ability to reliably estimate velocity in natural environments.
The authors report the generation of fluorescent false neurotransmitter 200 (FFN200), a new optical probe for selectively monitoring monoamine exocytosis in cultured neurons and brain slices. Using the new tool in combination with Ca2+ imaging, they find functionally silent dopaminergic vesicle clusters in the striatum, with impaired exocytosis at a step downstream from Ca2+ influx.
This study shows that the amount of linearly decodable information for categorical-orthogonal object tasks (for example, position, scale, pose, perimeter and aspect ratio) increases up the ventral visual hierarchy, ultimately matching human levels in inferior temporal cortex. It also provides a computational model that explains how this pattern of information arises.
This study demonstrates that fear memory expression is driven by 4-Hz oscillations in prefrontal–amygdala circuits. During fear behavior, prefrontal 4-Hz oscillations lead amygdala and synchronize spiking activity between the two structures. Ultimately, this study identifies 4-Hz oscillations as a physiological signature of fear memories.
The loss of nerve cells in the brain is the main event causing life-long deficits and neurological problems after stroke. Weilinger et al. show that NMDA receptors cause nerve cell death during stroke in an unexpected way. Although they require ligand binding and recruitment of downstream pannexin channels, NMDA receptors do not use the receptor's ion channel.
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.
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.
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.