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Cerebellar climbing fibers provide predictive, context-specific instructional signals that do not rely exclusively on motor errors to support learning of arbitrary sensorimotor associations.
Menegas et al. show that dopamine neurons projecting to the posterior striatum reinforce avoidance of threatening stimuli. Their results indicate that there are two axes of reinforcement learning using dopamine, the value axis and the threat axis.
The authors use integrative deconvolution of gene expression data to reveal core transcriptional features of CNS cell classes in humans, and identify cell-class-specific transcriptional differences in disease, among CNS regions, and between species.
The authors use single-nucleus RNA-seq to identify 10 GABAergic interneuron subtypes in human cortex layer 1. Molecular, morphological, and physiological evidence points to an emerging human cell type, the rosehip cell, not found in other species.
A GWAS of lifetime cannabis use reveals new risk loci, shows that cannabis use has genetic overlap with smoking and alcohol use, and indicates that the likelihood of initiating cannabis use is causally influenced by schizophrenia.
The authors describe microscopic channels that directly connect the skull marrow cavities with the meninges. Neutrophils originating from the skull marrow have a higher propensity to travel to the ischemic mouse brain than cells in the tibia.
Phagocytes drive formation & resolution of neuroinflammatory lesions. The authors use in vivo imaging to track expression of proinflammatory & resolution enzymes & follow temporal changes in individual phagocytes polarization states in inflamed CNS.
Controlling urination is a fundamental social need. Keller et al. develop a voluntary urination assay and uncover a subset of brainstem neurons that relax the urethral sphincter, providing insight into urinary control and its dysfunction.
This study shows that excitatory neurons in the ventral hippocampus that express the serotonin receptor 2c gene control attention through direct innervation of the mouse equivalent of the Edinger–Westphal nucleus.
Autism is ~4 times more common in males. Jung et al. reveal male-preponderant abnormal behaviors in mice lacking CHD8, a chromatin remodeler, accompanying sexually dimorphic changes in neuronal firing, synaptic transmission, and gene expression.
Burt et al. analyze patterns of gene expression across human cortex and show expression primarily varies along a sensory-association hierarchy captured by noninvasive neuroimaging, suggesting an organizing principle for microcircuit specialization.
Using a combination of in vivo recording and theoretical modeling, Campbell et al. develop a framework for understanding the integration of self-motion and landmark cues in entorhinal cortex and demonstrate that these principles extend to behavior.
By pairing cues with brief activation of dopamine neurons in absence of reward, the authors reveal elemental behaviors conditioned by dopamine, showing VTA underlies generation of incentive value and SNc supports conditioned movement invigoration.
Transposable elements, or ‘jumping genes’, constitute ~45% of the human genome. Sun et. al. report that jumping gene dysregulation is a pharmacologically targetable driver of cell death in neurodegenerative tauopathies, including Alzheimer’s disease.
Microglia clearance activity in adult brain is regulated epigenetically and region-specifically to match neuronal attrition rates. Uncoupling this activity from neural apoptosis leads to aberrant microglia activation & neurodegenerative-like changes.
Gollo et al. introduce random ‘mutations’ to the human connectome to study the trade-off between complexity vs. parsimony. The cortical hubs that are most fragile to these perturbations show the strongest loss of gray matter volume in schizophrenia.
Using genetically encoded physiological tools for monitoring, manipulating, and mapping discrete neural circuits, Giardino et al. characterize 2 discrete amygdala→hypothalamus pathways that promote opposite behavioral responses to emotional stimuli.
Through the development of novel PKC biosensors, the authors describe how PKCα, but not other classical isozymes, facilitates plasticity in dendritic regions through the integration of recent synaptic plasticity with current, local synaptic input.
Maternal stress during pregnancy is a risk factor for neurodevelopmental disorders. Jasarevic and colleagues show that the maternal vaginal microbiota partially mediates the lasting effects of prenatal stress on the gut and hypothalamus in mice.
This study describes a 3D human neuron-astrocyte-microglia triculture model of Alzheimer’s disease using a microfluidic platform and recapitulating plaque and tangle pathology, microglial recruitment, neuroinflammation, and cell death.