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Maintaining multiple items in working memory (WM) is central to human behavior. Persistently active neurons are thought to be a mechanism to maintain WMs, but it remains unclear how such activity is coordinated when multiple items are kept in memory. We show that memoranda-selective persistently active neurons in the human medial temporal lobe phase lock to ongoing slow-frequency (1-7 Hz) oscillations during WM maintenance. The properties of phase locking are dependent on memory content and load. During h...
Balance between excitation and inhibition (E-I balance) in neural circuits is believed to be tightly regulated. To the contrary, in this issue of Neuron, Bridi et al. (2020) reveal that inverse oscillations of synaptic inhibition and excitation lead to peaks and valleys in E-I balance across the 24 h day.
In this issue of Neuron, Ashrafi et al. (2020) identify a feedforward signaling mechanism that couples neuronal activity to the homeostatic maintenance of axonal and synaptic ATP production. This mechanism is achieved via changes in cytoplasmic calcium and activation of brain-specific, mitochondrial MICU3.
Confidence in perceptual decisions scales neural responses to violations in reward expectation. In this issue of Neuron, Lak et al. (2020) show that the medial prefrontal cortex in mice computes a confidence-dependent expectation signal that influences how dopamine neurons convey reward prediction errors to guide learning.
In this issue of Neuron, Greene et al. (2020) identify zones of network specificity and multi-network integration in the basal ganglia and thalamus of individual human subjects. Such information could aid in the development of personalized and more effective brain stimulation therapies for neuropsychiatric disorders.
Nonhuman primate neuroimaging is on the cusp of a transformation, much in the same way its human counterpart was in 2010, when the Human Connectome Project was launched to accelerate progress. Inspired by an open data-sharing initiative, the global community recently met and, in this article, breaks through obstacles to define its ambitions.
Stroke is one of the leading causes of long-term disability. Advanced technological solutions ("neurotechnologies") exploiting robotic systems and electrodes that stimulate the nervous system can increase the efficacy of stroke rehabilitation. Recent studies on these approaches have shown promising results. However, a paradigm shift in the development of new approaches must be made to significantly improve the clinical outcomes of neurotechnologies compared with those of traditional therapies. An "evolution...
The spatial distribution of large-scale functional networks on the cerebral cortex differs between individuals and is particularly variable in association networks that are responsible for higher-order cognition. However, it remains unknown how this functional topography evolves in development and supports cognition. Capitalizing on advances in machine learning and a large sample imaged with 27 min of high-quality functional MRI (fMRI) data (n = 693, ages 8-23 years), we delineate how functional topograph...
Current theories suggest that an error-driven learning process updates trial-by-trial to facilitate motor adaptation. How this process interacts with motor cortical preparatory activity-which current models suggest plays a critical role in movement initiation-remains unknown. Here, we evaluated the role of motor preparation during visuomotor adaptation. We found that preparation time was inversely correlated to variance of errors on current trials and mean error on subsequent trials. We also found causal ev...
Functional MRI and electrophysiology studies suggest that consciousness depends on large-scale thalamocortical and corticocortical interactions. However, it is unclear how neurons in different cortical layers and circuits contribute. We simultaneously recorded from central lateral thalamus (CL) and across layers of the frontoparietal cortex in awake, sleeping, and anesthetized macaques. We found that neurons in thalamus and deep cortical layers are most sensitive to changes in consciousness level, consiste...
Temporally organized reactivation of experiences during awake immobility periods is thought to underlie cognitive processes like planning and evaluation. While replay of trajectories is well established for the hippocampus, it is unclear whether the medial prefrontal cortex (mPFC) can reactivate sequential behavioral experiences in the awake state to support task execution. We simultaneously recorded from hippocampal and mPFC principal neurons in rats performing a mPFC-dependent rule-switching task on a plu...
Dopamine neurons mediate the association of conditioned stimuli (CS) with reward (unconditioned stimuli, US) by signaling the discrepancy between predicted and actual reward during the US. Some theoretical models suggest that learning is also influenced by the salience or associability of the CS. A hallmark of CS associability models is that they can explain latent inhibition, i.e., the observation that novel CS are more effectively learned than familiar CS. Novel CS are known to activate dopamine neurons, ...
The Cre-loxP system is invaluable for spatial and temporal control of gene knockout, knockin, and reporter expression in the mouse nervous system. However, we report varying probabilities of unexpected germline recombination in distinct Cre driver lines designed for nervous system-specific recombination. Selective maternal or paternal germline recombination is showcased with sample Cre lines. Collated data reveal germline recombination in over half of 64 commonly used Cre driver lines, in most cases with a ...
A current major challenge lies in controlling molecularly defined brain receptor and channel populations to investigate their function in vivo. In this issue of Neuron, Acosta-Ruiz et al. (2020) developed a highly versatile molecular toolkit to efficiently manipulate specific metabotropic glutamate receptor subtypes in brain circuits with light.
In this issue of Neuron, Dong et al. (2020) finds that deficiency of the psychiatric risk gene Cul3, which encodes an E3 ubiquitin ligase, leads to an upregulation of Cap-dependent protein translation. The resulting imbalance in protein synthesis and degradation is found to disrupt glutamatergic transmission and excitability in networks that underlie sociability and anxiety.
In this issue of Neuron, van Veluw et al. (2020) show that elimination of solutes from the brain along arterial walls is driven by low-frequency arteriolar oscillations and suggest that age-related reduction of this vasomotion may contribute to impaired clearance of Aβ.
A vast array of animal behavior-from locomotion to human speech-is thought to consist of different hierarchical levels, but its neural implementation remains poorly understood. In this issue of Neuron, Kaplan et al. (2020) identify neuronal circuit dynamics responsible for multiple levels and timescales of hierarchical locomotion control in Caenorhabditis elegans.
Cued spatial attention differentially modulates alpha power in attended relative to non-attended brain representations, termed the alpha asymmetry. Yet a causal role for alpha in attention is debated. In this issue of Neuron, Bagherzadeh et al., (2019) utilize neurofeedback to train alpha asymmetry and causally impact measures of spatial attention.
In a recent issue of Cell, Satterstrom et al. leverage de novo high-impact variants to identify 102 genes associated with autism spectrum disorder (ASD). Most of these genes have roles in regulation of gene expression or neuronal communication, implicating both developmental and functional changes in ASD.
An international group of researchers met in November 2019 in Beijing to explore the intersection of neuroscience and AI. The aim was to offer a fertile ground for stimulating discussions and ideas, including issues such as policy making and the future of neuroscience and AI across the globe.
Evolution is a blind fitting process by which organisms become adapted to their environment. Does the brain use similar brute-force fitting processes to learn how to perceive and act upon the world? Recent advances in artificial neural networks have exposed the power of optimizing millions of synaptic weights over millions of observations to operate robustly in real-world contexts. These models do not learn simple, human-interpretable rules or representations of the world; rather, they use local computation...
An internal sense of heading direction is computed from various cues, including steering maneuvers of the animal. Although neurons encoding heading and steering have been found in multiple brain regions, it is unclear whether and how they are organized into neural circuits. Here we show that, in flying Drosophila, heading and turning behaviors are encoded by population dynamics of specific cell types connecting the subregions of the central complex (CX), a brain structure implicated in navigation. Columnar ...
Unbiased in vivo genome-wide genetic screening is a powerful approach to elucidate new molecular mechanisms, but such screening has not been possible to perform in the mammalian central nervous system (CNS). Here, we report the results of the first genome-wide genetic screens in the CNS using both short hairpin RNA (shRNA) and CRISPR libraries. Our screens identify many classes of CNS neuronal essential genes and demonstrate that CNS neurons are particularly sensitive not only to perturbations to synaptic ...
Presynaptic neurexins (Nrxs) and type IIa receptor-type protein tyrosine phosphatases (RPTPs) organize synapses through a network of postsynaptic ligands. We show that leucine-rich-repeat transmembrane neuronal proteins (LRRTMs) differentially engage the protein domains of Nrx but require its heparan sulfate (HS) modification to induce presynaptic differentiation. Binding to the HS of Nrx is sufficient for LRRTM3 and LRRTM4 to induce synaptogenesis. We identify mammalian Nrx1γ as a potent synapse organizer...