Before the onset of sensory transduction, developing neural circuits spontaneously generate correlated activity in distinct spatial and temporal patterns. During this period of patterned activity, sensory maps develop and initial coarse connections are refined, which are critical steps in the establishment of adult neural circuits. Over the last decade there has been substantial evidence that altering the pattern of spontaneous activity disrupts refinement, but the mechanistic understanding of this process remains incomplete. In this review, we discuss recent experimental and theoretical progress towards the process of activity-dependent refinement, focusing on circuits in the visual, auditory and motor systems. While many outstanding questions remain, the combination of several novel approaches have brought us closer to a comprehensive understanding of how complex neural circuits are established by patterned spontaneous activity during development.

Schizophrenia is characterized by impaired cognitive control associated with prefrontal cortex dysfunction, but the underlying pathophysioloical mechanisms remain unknown. Higher cognitive processes are associated with cortical oscillations in the gamma range, which are also impaired in chronic schizophrenia. We tested whether cognitive control-related gamma deficits are observed in firstepisode patients, and whether they are associated with antipsychotic medication exposure. Fifty-three first-episode schizophrenia patients (21 without antipsychotic medication treatment) and 29 healthy control subjects underwent electroencephalography (EEG) during performance of a preparatory cognitive control task (preparing to overcome prepotency or POP task). The first-episode schizophrenia patient group was impaired (relative to the control group) on task performance and on delay-period gamma power at each of the three subgroups of frontal electrodes. The unmedicated patient subgroup was similarly impaired compared with controls, and was not different on these measures compared with the medicated patient subgroup. In contrast, delay-period theta power was not impaired in the full patient group nor in the unmedicated patient subgroup. Impaired cognitive control-related gamma cortical oscillatory activity is present at the first psychotic episode in schizophrenia, and is independent of medication status. This suggests that altered local circuit function supporting high-frequency oscillatory activity in prefrontal cortex ensembles may serve as the pathophysiological substrate of cognitive control deficits in schizophrenia.

For reasons that remain insufficiently understood, the brain requires among the highest levels of metals in the body for normal function. The traditional paradigm for this organ and others is that fluxes of alkali and alkaline earth metals are required for signaling, but transition metals are maintained in static, tightly bound reservoirs for metabolism and protection against oxidative stress. Here we show that copper is an endogenous modulator of spontaneous activity, a property of functional neural circuitry. Using Copper Fluor-3 (CF3), a new fluorescent Cu + sensor for one-and twophoton imaging, we show that neurons and neural tissue maintain basal stores of loosely bound copper that can be attenuated by chelation, which define a labile copper pool. Targeted disruption of these labile copper stores by acute chelation or genetic knockdown of the CTR1 (copper transporter 1) copper channel alters the spatiotemporal properties of spontaneous activity in developing hippocampal and retinal circuits. The data identify an essential role for copper neuronal function and suggest broader contributions of this transition metal to cell signaling.copper signaling | fluorescent sensor | molecular imaging | neural activity

MethodsMethod S1: Screening of the expressed candidate sex determinants Developing anthers at stage 1-2, which correspond to the differentiation stage of male or female androecium (see Supplementary Figure S1), were sampled from F1 sibling vines derived from an interspecific cross, A. rufa sel. Fuchu × A. chinensis sel. FCM1, named KE population (15), planted on Kagawa University, Japan (N34.28, E134.13), in 10-22 April in 2016-2017. Total RNA was extracted using the Plant RNA Reagent (Invitrogen) and purified by phenol/chloroform extraction. Two micrograms of total RNA were processed in preparation for Illumina Sequencing, according to a previous report (15). The constructed libraries were sequenced on Illumina's HiSeq 4000 sequencer (50-bp single-end or 150-bp paired-end reads). All Illumina sequencing were conducted at the Vincent J. Coates Genomics Sequencing Laboratory at UC Berkeley, and the raw sequencing reads were processed using custom Python scripts developed in the Comai laboratory and available online (http://comailab.genomecenter.ucdavis.edu/index.php/), as previously described (9). Male-specific Ychromosomal sequences in kiwifruit, defined MSY contigs, were comprehensively identified in previous study (15). The mRNA-Seq reads from each 5 male and female individuals from the KE population (Supplemental Table S11) (15) were used to identify the genes substantially expressed in developing anthers. The mRNA-Seq reads were aligned to the hypothetical 61 genes located on the 249 MSY contigs (Akagi et al. 2018), using the Burrows-Wheeler Aligner (BWA) (37) allowing up to ca 3% mismatches. The number of reads mapping to each contigs was recorded from the alignment file produced by the Sequence Alignment/Map (SAM) tool (38) (http://samtools.sourceforge.net/). For Friendly Boy (FrBy), which showed male-specific and anther-enriched expression, the expression patterns were further examined using various plant organs and developing anthers (stage 2a, 2b, 3a, and 3b, see Supplementary Figure S1). Method S2: Expression profiling in kiwifruit antherThe described mRNA-Seq reads from each 5 male and female individuals of the KE population were aligned to the whole CDS sequences sets in A. chinensis (27), using BWA with default parameters. The number of reads mapped to each reference sequences was recorded from the alignment file produced by the Sequence Alignment/Map (SAM) tool (38) (http://samtools.sourceforge.net/). The read counts per gene were generated from the aligned SAM files using a custom R script. Differential expression between male and female individuals was analysed in R (version 3.0.1) using the R package DESeq (Anders and Huber, 2010) (version 1.14; http://bioconductor.org/packages/release/bioc/html/DESeq.html). We conducted DESeq analysis using 5 biological replicates from male and female individuals, with the following parameters: method='per-condition' and sharingMode='maximum'. An FDR threshold of 0.1 was used to identify differentially expressed genes. Method S3: in situ RNA hybridizationRNA in ...

Human memory and Internet search engines face a shared computational problem, needing to retrieve stored pieces of information in response to a query. We explored whether they employ similar solutions, testing whether we could predict human performance on a fluency task using PageRank, a component of the Google search engine. In this task, people were shown a letter of the alphabet and asked to name the first word beginning with that letter that came to mind. We show that PageRank, computed on a semantic network constructed from word-association data, outperformed word frequency and the number of words for which a word is named as an associate as a predictor of the words that people produced in this task. We identify two simple process models that could support this apparent correspondence between human memory and Internet search, and relate our results to previous rational models of memory.

Research into the microbiomes of natural environments is changing the way ecologists and evolutionary biologists view the importance of microbes in ecosystem function. This is particularly relevant in ocean environments, where microbes constitute the majority of biomass and control most of the major biogeochemical cycles, including those that regulate the Earth's climate. Coastal marine environments provide goods and services that are imperative to human survival and well-being (e.g. fisheries, water purification), and emerging evidence indicates that these ecosystem services often depend on complex relationships between communities of microorganisms (the 'microbiome') and their hosts or environment -termed the 'holobiont'. Understanding of coastal ecosystem function must therefore be framed under the holobiont concept, whereby macroorganisms and their associated microbiomes are considered as a synergistic ecological unit. Here we evaluated the current state of knowledge on coastal marine microbiome research and identified key questions within this growing research area. Although the list of questions is broad and ambitious, progress in the field is increasing exponentially, and the emergence of large, international collaborative networks and well-executed manipulative experiments are rapidly advancing the field of coastal marine microbiome research.

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Gap junction coupling synchronizes activity among neurons in adult neural circuits, but its role in coordinating activity during development is less known. The developing retina exhibits retinal waves - spontaneous depolarizations that propagate among retinal interneurons and drive retinal ganglion cells to fire correlated bursts of action potentials. During development, two connexin isoforms, connexin36 (Cx36) and Cx45, are expressed in bipolar cells and retinal ganglion cells (RGCs), and therefore provide a potential substrate for coordinating network activity. To determine whether gap junctions contribute to retinal waves, we compared spontaneous activity patterns using calcium imaging, whole-cell recording and multielectrode array recording in control, single knockout (ko) mice lacking Cx45 and double knockout (dko) mice lacking both isoforms. Wave frequency, propagation speed and bias in propagation direction were similar in Ctr, Cx36ko, Cx45ko and Cx36/45dko retinas. However, the spontaneous firing rate of individual retinal ganglion cells was elevated in Cx45ko retinas, similar to Cx36ko retinas (Hansen et al., 2005; Torborg and Feller, 2005), a phenotype that was more pronounced in Cx36/45dko retinas. As a result, spatial correlations, as assayed by nearest neighbor correlation and functional connectivity maps, were significantly altered. In addition, Cx36/45dko mice had reduced eye-specific segregation of retinogeniculate afferents. Together, these findings suggest that although Cx36 and Cx45 do not play a role in gross spatial and temporal propagation properties of retinal waves, they strongly modulate the firing pattern of individual RGCs, ensuring strongly correlated firing between nearby RGCs and normal patterning of retinogeniculate projections.