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Biology subjects

Wilson, A. M.

Publications and source records attributed to Wilson, A. M..

At least 19 recordsLinked to original sources

Single nucleus RNA sequencing and spatial transcriptomics reveal unique functionalities of gray matter versus white matter oligodendrocytes in aging and Alzheimer's Disease

Oligodendrocyte (OL) dysfunction and white-matter (WM) vulnerability are increasingly recognized as important aspects of aging and Alzheimer's Disease (AD), yet human WM-focused, cellular-resolution transcriptomic data remain limited. Here, we profiled prefrontal WM from 48 brain donors spanning young adulthood and late-life with low versus high AD Neuropathologic Change (ADNC) using single-nucleus RNA sequencing followed by spatial transcriptomics (CosMx) in a subset of matched donors. We integrated aged WM OLs with a reference dorsolateral prefrontal cortex grey-matter (GM) OL dataset (SEA-AD) to define region- and pathology-associated OL programs. Across modalities, GM OLs exhibited a robust synapse/neurotransmitter-associated transcriptional signature relative to WM OLs, whereas this program was reduced with aging and attenuated in high ADNC GM. In contrast, WM OLs showed stronger immune-associated programs with aging and further enhancement in high ADNC, including cytokine/chemokine signaling and antigen presentation-related pathways. High ADNC WM OLs also displayed amplified proteostasis and stress-adaptation signatures, including selective upregulation of chaperone/heat shock genes and ferritin subunits, consistent with increased protein-folding demand and altered iron handling. To resolve OL state organization beyond static differential expression, we annotated OL sub-states using marker panels and inferred pseudotime-guided directional state-to-state flows within each tissue/condition stratum. This analysis identified a conserved newly formed differentiating (NFOL)/differentiating [->] lipid remodeling (APOE/ABCA1/LPL+) [->] Stress/ISR-reactive architecture, with a pronounced expansion of the Stress/ISR-reactive compartment and altered transition-associated pathway enrichment in high ADNC WM. Together, these data define WM-specific OL programs linked to aging and ADNC and nominate a stress/immune-enriched OL state landscape consistent with a putative senescence-like phenotype in diseased WM.

neuroscience↗

Improving the production and virulence of entomopathogenic fungi for biological control using insect-derived in vitro culture medium

BackgroundThe environment in which a fungus grows can directly influence their development, transmission, and pathogenic potential. This environment encompasses factors like nutrient availability, biotic and abiotic stressors, as well as host-derived chemical cues. In fungal pathogens, where conidia act as the infectious agents, the environment impacts the quantity and quality of these spores, thereby aOecting their ability to infect and kill hosts. In the present study, we investigated the effect of host-derived medium types on various phenotypes, including spore production, growth rate, and virulence in two entomopathogenic fungi, Metarhizium acridum and Metarhizium brunneum. Three medium types derived from insect material were compared to a standard laboratory medium. ResultsConidia produced on the insect-derived media exhibited enhanced sporulation and reduced time to sporulation, while conidial germination and maximum growth rate were comparable across medium types, suggesting that some of the medium-induced phenotypic effects were transient. Notably, conidia derived from two of the insect medium types demonstrated higher virulence, indicating that host-derived cues may prime virulence. ConclusionThese results highlight that the composition of growth substrates can regulate fungal reproductive strategies and virulence, with implications for developing high-throughput phenotyping and for the biotechnological optimization of mass production and efficacy of entomopathogenic fungi in biological control applications. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=106 SRC="FIGDIR/small/711814v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@189013eorg.highwire.dtl.DTLVardef@1b0cedborg.highwire.dtl.DTLVardef@dccb4eorg.highwire.dtl.DTLVardef@1a77895_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

Homothallic or heterothallic? A genomic investigation into the sexual capabilities of the ascomycete fungus Clonostachys rosea

Modes of reproduction and sexual strategies strongly influence the genetic diversity and evolutionary potential of a species. The ascomycete fungus Clonostachys rosea is reported to be homothallic (sexually self-fertile), although a rapid decay of genome-wide linkage disequilibrium is also reported, something that is not in line with an obligate homothallic mode of reproduction. To investigate this phenomenon, we identified the mating-type (MAT1) locus in 66 genome-sequenced C. rosea strains under the hypothesis that each strain contains genes from both MAT1 idiomorphs. Eleven strains indeed contained both MAT1-1 and MAT1-2 genes, suggesting homothallism. However, most strains harboured either MAT1-1 or MAT1-2 genes and co-existed in North America, Europe and China, suggesting heterothallism. The MAT1 locus of heterothallic strains was highly conserved, and the linkage disequilibrium half decay distance was 1050 bp, suggesting sexual outcrossing. The presence of conserved MAT1-1 or MAT1-2 idiomorphs in strains of other Clonostachys species shows that heterothallism is likely the ancestral state. A phylogenetic analysis of 2800 single-copy orthologous genes revealed that homothallic and heterothallic strains separated in two well-supported clades, indicating a single lineage of homothallic C. rosea, likely originating in South America, followed by intercontinental dispersal. Homothallic C. rosea strains displayed higher nucleotide diversity than heterothallic strains, indicating a lack of outcrossing. This unique case of both homothallic and heterothallic lineages within the same species provides an opportunity to study the genomic consequences of selfing in very closely related strains.

evolutionary biology↗

Developmental Connectomics of the Mouse Cerebellum

To uncover the developmental processes that establish the precise patterns of synaptic connectivity in the CNS, we employed a connectomic approach in the mouse cerebellar cortex between birth and 2 weeks of age. There were dramatic quantitative and qualitative changes in the structure and connectivity of cerebellar cells. Parallel fiber synapses onto Purkinje cells increased [~]500-fold, with the most rapid growth taking place a week after birth. To support this profound synaptogenesis, Purkinje cells generated thousands of transient parallel fiber-oriented filopodia that received nascent synapses from parallel fibers. Importantly, we find that granule cells initiate synaptic output onto Purkinje cells only after receiving mossy fiber input, revealing a sequential, input-dependent logic for circuit assembly. In sharp contrast to the concurrent pruning of climbing fiber inputs, parallel fiber connectivity expanded and became highly individualized during development. Despite anatomical overlap, neighboring Purkinje cells share significantly fewer parallel fiber inputs than expected by chance. Moreover, parallel fibers themselves diverged spatially, further enforcing selective input allocation and resulting in highly specific parallel fiber cohorts for each Purkinje cell. Our findings uncover a mechanistic sequence in which early afferent activity and transient cellular structures guide the selective wiring and expansion of parallel fiber input to Purkinje cells, establishing developmental principles that ensure functional specificity in the mature brain.

neuroscience↗

Genome compartmentalization in a host-specific fungal insect pathogen reveals a putative mating type locus on an accessory chromosome

The genomic diversity of many fungal pathogens is driven by rapidly evolving regions harbouring significant amounts of transposable elements. Such genomic regions often contain genes important for pathogenicity and may be sequestered from the core genome on accessory chromosomes, which are variably present in isolates of a species. In this study, we present a pangenomic analysis of a fungal insect pathogen, Metarhizium acridum, using seven chromosome-scale genomes from four different continents. We show that approximately 25% of the M. acridum pangenome is comprised of genes only present in one isolate (singletons) or more than one but not all isolates (accessory). These genes are enriched for functions in secondary metabolite production, nutrient transport, and chromosome organization. We also find evidence of functional compartmentalization of the genome, as the core genome of M. acridum is enriched in carbohydrate-active enzymes, while the accessory components are enriched in effectors that are located in gene-sparse regions of the genome. Furthermore, we identified the first naturally recovered accessory chromosome in M. acridum, which does not harbor effector or secondary metabolite proteins related to host-insect interactions but is enriched in functions related to sexual reproduction. Within the genus Metarhizium, M. acridum is one of few species considered to regularly reproduce sexually. We show that the accessory chromosome contains genes from both the MAT1-1 and MAT1-2 idiomorphs, in addition to the MAT locus found on the core chromosomes. Our findings suggest that the presence of this accessory chromosome may facilitate sexual reproduction, possibly even primary homothallism, in the otherwise heterothallic M. acridum. Overall, our study presents a putative novel mechanism whereby this fungal pathogen may acquire gene recombination and ensure maintenance of the accessory chromosome.

microbiology↗

Transcriptional impacts of substance use disorder and HIV on human ventral midbrain neurons and microglia

For people with HIV (PWH), substance use disorders (SUDs) are a prominent neurological risk factor, and the impacts of both on dopaminergic pathways are a potential point of deleterious convergence. Here, we profile, at single nucleus resolution, the substantia nigra (SN) transcriptomes of 90 postmortem donors in the context of chronic HIV and opioid/cocaine SUD, including 67 prospectively characterized PWH. We report altered microglial expression for hundreds of pro- and anti-inflammatory regulators attributable to HIV, and separately, to SUD. Stepwise, progressive microglial dysregulation, coupled to altered SN dopaminergic and GABAergic signaling, was associated with SUD/HIV dual diagnosis and further with lack of viral suppression in blood. In virologically suppressed donors, SUD comorbidity was associated with microglial transcriptional changes permissive for HIV infection. We report HIV-related downregulation of monoamine reuptake transporters specifically in dopaminergic neurons regardless of SUD status or viral load, and additional transcriptional signatures consistent with selective vulnerability of SN dopamine neurons.

genomics↗

3D reconstruction of the cerebellar germinal layer reveals intercytoplasmic connections between developing granule cells

SummaryThe difficulty of retrieving high-resolution, in vivo evidence of the proliferative- and migratory processes occurring in neural germinal zones has limited our understanding of neurodevelopmental mechanisms. Here, we employed a connectomic approach using a high-resolution, serial-sectioning scanning electron microscopy volume to investigate the laminar cytoarchitecture of the transient external granular layer (EGL) of the developing cerebellum, where granule cells coordinate a series of mitotic and migratory events. By integrating image segmentation, 3D reconstruction, and deep learning approaches, we discovered and characterized anatomically complex intercellular connections bridging pairs of cerebellar granule cells throughout the EGL. Connected cells were either mitotic, migratory, or transitioning between these two cell stages, displaying a chronological continuum of proliferative and migratory events never previously observed in vivo at this resolution. This unprecedented ultra-structural characterization poses intriguing hypotheses about intercellular connectivity between developing progenitors, and its possible role in the development of the central nervous system (CNS).

neuroscience↗

Uncovering features of synapses in primary visual cortex through contrastive representation learning

3D EM connectomics image volumes are now surpassing sizes of 1 mm3, and are therefore beginning to contain multiple meaningful spatial scales of brain circuitry simultaneously. However, the sheer density of information in such datasets makes the development of unbiased, scalable machine learning techniques a necessity for extracting novel insights without extremely time-consuming, intensive labor. In this paper, we present SynapseCLR, a self-supervised contrastive representation learning method for 3D electron microscopy (EM) data, and use the method to extract feature representations of synapses from a 3D EM dataset from mouse visual cortex. We show that our representations separate synapses according to both their overall physical appearance and structural annotations of known functional importance. We further demonstrate the utility of our methodology for several valuable downstream tasks for the growing field of 3D EM connectomics. These include one-shot identification of defective synapse segmentations, dataset-wide similarity-based querying, and accurate imputation of annotations for unlabeled synapses, using only manual annotation of 0.2% of synapses in the dataset. In particular, we show that excitatory vs. inhibitory neuronal cell types can be assigned to individual synapses and highly truncated neurites with accuracy exceeding 99.8%, making this population accessible to connectomics analysis. Finally, we present a data-driven and unsupervised study of the manifold of synaptic structural variation, revealing its intrinsic axes of variation and showing that synapse structure is also strongly correlated with inhibitory neuronal subtypes.

neuroscience↗

Range contractions of the Broad-winged Hawk in the Northeast United States

The Broad-winged Hawk (BWHA, Buteo platypterus) is a small, secretive hawk with distinguishing broad black tail bands that breeds in northeastern North America. The hawk nests in deciduous or mixed forest, often near water, and close to clearings or forest edges. Land conversion and fragmentation alters the landscape and reduces the area of contiguous forest used by BWHA. This study seeks to determine the landscape characteristics influencing the apparent breeding range declines of the BWHA at the landscape scale. Landscape characteristics and BWHA presence data from 18,684 Breeding Bird Atlas blocks (each about 25km2) from Ohio, West Virginia, Maryland, Pennsylvania, and New York for two atlas period (1st Atlas: 1980s, 2nd Atlas: 2000s) were analyzed. Bayesian latent Gaussian models were fitted using INLA to determine best fit model for predicting the landscape characteristics associated with BWHA presence. The best models included landscape changes in land cover, including forest, water, urban, barren, farmland, and wetland and fragmentation of the landscape. Trends in loss were especially prevalent around the regions largest cities: New York, Philadelphia, Baltimore and Washington DC. Loss of BWHA at the block-level was associated with areas with less forest in the 2000s, a decline in size of largest forest patches, lower elevations and lower latitudes. We suggest that both habitat loss and climate change may be contributing to the range contraction of the Broad-winged Hawk in the northeast United States.

ecology↗

Oligodendrocyte precursor cells prune axons in the mouse neocortex

Neurons in the developing brain undergo extensive structural refinement as nascent circuits adopt their mature form1. This transformation is facilitated by the engulfment and degradation of excess axonal branches and inappropriate synapses by surrounding glial cells, including microglia and astrocytes2,3. However, the small size of phagocytic organelles and the complex, highly ramified morphology of glia has made it difficult to determine the contribution of these and other glial cell types to this process. Here, we used large scale, serial electron microscopy (ssEM) with computational volume segmentation to reconstruct the complete 3D morphologies of distinct glial types in the mouse visual cortex. Unexpectedly, we discovered that the fine processes of oligodendrocyte precursor cells (OPCs), a population of abundant, highly dynamic glial progenitors4, frequently surrounded terminal axon branches and included numerous phagolysosomes (PLs) containing fragments of axons and presynaptic terminals. Single- nucleus RNA sequencing indicated that cortical OPCs express key phagocytic genes, as well as neuronal transcripts, consistent with active axonal engulfment. PLs were ten times more abundant in OPCs than in microglia in P36 mice, and declined with age and lineage progression, suggesting that OPCs contribute very substantially to refinement of neuronal circuits during later phases of cortical development.

neuroscience↗

Multiscale and multimodal reconstruction of cortical structure and function

We present a semi-automated reconstruction of L2/3 mouse primary visual cortex from 3 million cubic microns of electron microscopic images, including pyramidal and inhibitory neurons, astrocytes, microglia, oligodendrocytes and precursors, pericytes, vasculature, mitochondria, and synapses. Visual responses of a subset of pyramidal cells are included. The data are being made publicly available, along with tools for programmatic and 3D interactive access. The density of synaptic inputs onto inhibitory neurons varies across cell classes and compartments. We uncover a compartment-specific correlation between mitochondrial coverage and synapse density. Frequencies of connectivity motifs in the graph of pyramidal cells are predicted quite accurately from node degrees using the configuration model of random graphs. Cells receiving more connections from nearby cells exhibit stronger and more reliable visual responses. These example findings illustrate the resources utility for relating structure and function of cortical circuits as well as for neuronal cell biology.

neuroscience↗

Vulnerability of Elevation-Restricted Endemic Birds of the Cordillera de Talamanca (Costa Rica and Panama) to Climate Change

Animals endemic to tropical mountains are known to be especially vulnerable to climate change. The Cordillera de Talamanca (Costa Rica and Panama) is a geographically isolated mountain chain and global biodiversity hotspot, home to more than 50 endemic bird species. We used eBird community science observations to predict the distributions of a suite of 48 of these endemic birds in 2006-2015, and in 2070, under four climate change scenarios. Species distributions were predicted using program Maxent, incorporating elevation, satellite derived habitat data, and WorldClim climate variables. Model fit, as assessed by Area under the Receiver Operator Curve (AUC) was very high for most species, ranging from 0.877 to 0.992 (mean of 0.94). We found that most species are predicted to undergo range contractions by 2070, with a mean of 15% under modest climate change (RCP 2.6) up to a mean of 40% under more severe climate change (RCP 8.5). Most of the current ranges of these species are within existing protected areas (average of 59% in 2006-2015), and with prospective range contractions, the importance of these protected areas is forecast to increase. We suggest that these predicted range declines should elevate conservation concerns for this suite of species, and vigilance, in the form of better population monitoring, is urgently needed.

ecology↗

Airborne point counts: a method for estimating songbird abundance with drones

Using drones to conduct airborne bioacoustic surveys is a potentially useful new way to estimate the abundance of vocal bird species. Here we show that by using two recording devices suspended from a quadcopter drone it is possible to estimate distances to birds with precision. In an experimental test, the mean error of our estimated distances to a broadcast song across 11 points between 0 and 100 m away was just 3.47 m. In field tests we compared 1-minute airborne counts with 5-minute terrestrial counts at 34 count locations. We found that the airborne counts yielded similar data to the terrestrial point counts for most of the 10 the songbirds included in our analysis, and that the effective detection radii were also similar. However, airborne counts significantly under-detected the Northern Cardinal ({chi}29 = 22.8, post-hoc test P = 0.007), which we attribute to a behavioral response to the drone. Airborne counts work best for species that vocalize close to the ground and have high frequency-range songs. Under those circumstances, airborne bioacoustics could have several advantages over ground-based surveys, including increased precision, increased repeatability, and easier access in difficult terrain. Further, we show that it is possible to do rapid surveys using airborne techniques, which could lead to the development of much more efficient survey protocols than are possible using traditional survey techniques. Lay SummaryO_LIWe show that it is possible to estimate the distance of singing birds from a drone, which then allows bird counts to be converted to true abundance or population densities. C_LIO_LIUsing drones to count birds allows researchers to survey areas that may be difficult or dangerous to access on foot. C_LIO_LIAirborne counts are potentially a highly efficient and highly repeatable way to estimate populations of vocal bird species. C_LI

ecology↗

Species-Specific Responses of Bird Song Output in the Presence of Drones

Drones are now widely used to study wildlife, but applications for studying bioacoustics have been limited. Drones can be used to collect data on bird vocalizations, but an ongoing concern is that noise from the drones could change bird vocalization behavior. To test this behavioral impact we conducted an experiment using 30 sound localization arrays to track the song output of seven songbird species before, during, and after a 3-minute flight of a small quadcopter drone hovering at 50 m above ground level. We analyzed 8,303 song bouts, of which 2,285 song bouts of 184 individual birds were within 50 meters of the array centers. We used linear mixed effect models to assess patterns in song output showed patterns that could be attributed to the drones presence. We found no evidence of any effect of the drone for five species: American Robin Turdus migratorius, Common Yellowthroat Geothlypis trichas, Field Sparrow Spizella pusilla, Song Sparrow Melospiza melodia, and Indigo Bunting Passerina cyanea. However, we found a substantial decrease in Yellow Warbler Setophaga petechia song detections during the 3-minute drone hover, such that there was an 81% drop in detections in the 3rd minute (Wald-test, p<0.001), compared with before the drones introduction. In contrast, the number of singing Northern Cardinal Cardinalis cardinalis increased after the drone was introduced, and remained almost five-fold higher for 4-minutes after the drone departed (P<0.001). Further, we found an increase in cardinal contact/alarm calls when the drone was overhead, with the elevated calling-rate sustaining for 2 minutes after the drone had departed (P<0.001). Our study suggests that responses of songbirds to drones may be species-specific, an important consideration when proposing the use of drones in avian studies. We note that recent advances in drone technology have resulted in much quieter drones, which makes us hopeful that the impacts that we detected could be greatly reduced.

ecology↗

Binary and analog variation of synapses between cortical pyramidal neurons

Learning from experience depends at least in part on changes in neuronal connections. We present the largest map of connectivity to date between cortical neurons of a defined type (L2/3 pyramidal cells), which was enabled by automated analysis of serial section electron microscopy images with improved handling of image defects. We used the map to identify constraints on the learning algorithms employed by the cortex. Previous cortical studies modeled a continuum of synapse sizes (Arellano et al. 2007) by a log-normal distribution (Loewenstein, Kuras, and Rumpel 2011; de Vivo et al. 2017; Santuy et al. 2018). A continuum is consistent with most neural network models of learning, in which synaptic strength is a continuously graded analog variable. Here we show that synapse size, when restricted to synapses between L2/3 pyramidal cells, is well-modeled by the sum of a binary variable and an analog variable drawn from a log-normal distribution. Two synapses sharing the same presynaptic and postsynaptic cells are known to be correlated in size (Sorra and Harris 1993; Koester and Johnston 2005; Bartol et al. 2015; Kasthuri et al. 2015; Dvorkin and Ziv 2016; Bloss et al. 2018; Motta et al. 2019). We show that the binary variables of the two synapses are highly correlated, while the analog variables are not. Binary variation could be the outcome of a Hebbian or other synaptic plasticity rule depending on activity signals that are relatively uniform across neuronal arbors, while analog variation may be dominated by other influences. We discuss the implications for the stability-plasticity dilemma.

neuroscience↗

Separable codes for read-out of mouse primary visual cortex across attentional states

Attentional modulation of neuronal activity in sensory cortex could alter perception by enhancing the local representation of attended stimuli or its behavioral read-out downstream. We tested these hypotheses using a task in which mice are cued on interleaved trials to attend visual or auditory targets. Neurons in primary visual cortex (V1) that encode task stimuli have larger visually-evoked responses when attention is directed toward vision. To determine whether the attention-dependent changes in V1 reflect changes in representation or read-out, we decoded task stimuli and choices from population activity. Surprisingly, both visual and auditory choices can be decoded from V1, but decoding takes advantage of unique activity patterns across modalities. Furthermore, decoding of choices, but not stimuli, is impaired when attention is directed toward the opposite modality. The specific effect on choice suggests behavioral improvements with attention are largely due to targeted read-out of the most informative V1 neurons.

neuroscience↗

Unique spatial integration in mouse primary visual cortex and higher visual areas

Neurons in the visual system integrate over a wide range of spatial scales. This diversity is thought to enable both local and global computations. To understand how spatial information is encoded across the mouse visual system, we use two-photon imaging to measure receptive fields in primary visual cortex (V1) and three downstream higher visual areas (HVAs): LM (lateromedial), AL (anterolateral) and PM (posteromedial). We find significantly larger receptive field sizes and less surround suppression in PM than in V1 or the other HVAs. Unlike other visual features studied in this system, specialization of spatial integration in PM cannot be explained by specific projections from V1 to the HVAs. Instead, our data suggests that distinct connectivity within PM may support the areas unique ability to encode global features of the visual scene, whereas V1, LM and AL may be more specialized for processing local features.

neuroscience↗

The rich get richer: synaptic remodeling between climbing fibers and Purkinje cells in the developing cerebellum begins with positive feedback addition of synapses.

During postnatal development, cerebellar climbing fibers strongly innervate a subset of their original Purkinje cell targets and eliminate their connections from the rest. In the adult, each climbing fiber innervates a small number of Purkinje cells and each Purkinje cell is innervated by a single climbing fiber. To get insight about the processes responsible for this remapping, we reconstructed serial electron microscopy datasets from mice during the first postnatal week. In contrast to adult connectivity, individual neonatal climbing fibers innervate many nearby Purkinje cells, and multiple climbing fibers innervate each Purkinje cell. Between postnatal days 3 and 7, Purkinje cells retract long dendrites and grow many proximal dendritic processes. On this changing landscape, individual climbing fibers selectively add many synapses to a subset of Purkinje cell targets in a positive-feedback manner, without pruning synapses from other Purkinje cells. The active zone sizes of synapses associated with powerful versus weak inputs are indistinguishable. These results show that changes in synapse number rather than synapse size are the predominant form of early developmental plasticity. Finally, although multiple climbing fibers innervate each Purkinje cell in early postnatal development, the number of climbing fibers and Purkinje cells in a local cerebellar region nearly match. Thus, initial over-innervation of Purkinje cells by climbing fibers is economical, in that the number of axons entering a region is enough to assure that each axon ends up with a postsynaptic target, and that none branched there in vain.\n\nHIGHLIGHTSO_LIDeveloping climbing fibers establish synapses on many neighboring Purkinje cells unlike the sparse pattern of innervation in later life\nC_LIO_LIClimbing fibers add many synapses onto a few of their Purkinje targets before the pruning stage in a rich-get-richer type process\nC_LIO_LIThe synapse sizes of strengthened and weakened climbing fiber inputs are indistinguishable.\nC_LIO_LIExuberant branching of climbing fiber axons in early postnatal life appears to be economical because the numbers of axons and Purkinje cells in a local region match, ensuring that each axon can establish a long-lasting connection there\nC_LI\n\nBLURBHigh-resolution serial electron microscopy reconstructions reveal that climbing fiber-Purkinje cell synaptic refinement in the developing cerebellum begins with significant synapse addition. Climbing fibers focus their synapses onto a smaller number of Purkinje cells by selectively adding synapses onto some target cells. All axons that project to a region in development play a role in the final connectivity.

neuroscience↗