Animals exhibit innate behaviours to a variety of sensory stimuli including olfactory cues. In
, one higher olfactory centre, the lateral horn (LH), is implicated in innate behaviour. However, our ...structural and functional understanding of the LH is scant, in large part due to a lack of sparse neurogenetic tools for this region. We generate a collection of split-GAL4 driver lines providing genetic access to 82 LH cell types. We use these to create an anatomical and neurotransmitter map of the LH and link this to EM connectomics data. We find ~30% of LH projections converge with outputs from the mushroom body, site of olfactory learning and memory. Using optogenetic activation, we identify LH cell types that drive changes in valence behavior or specific locomotor programs. In summary, we have generated a resource for manipulating and mapping LH neurons, providing new insights into the circuit basis of innate and learned olfactory behavior.
A major roadblock in realizing large-scale production of hydrogen via electrochemical water splitting is the cost and inefficiency of current catalysts for the oxygen evolution reaction (OER). ...Computational research has driven important developments in understanding and designing heterogeneous OER catalysts using linear scaling relationships derived from computed binding energies. Herein, we interrogate 17 of the most active molecular OER catalysts, based on different transition metals (Ru, Mn, Fe, Co, Ni, and Cu), and show they obey similar scaling relations to those established for heterogeneous systems. However, we find that the conventional OER descriptor underestimates the activity for very active OER complexes as the standard approach neglects a crucial one-electron oxidation that many molecular catalysts undergo prior to O-O bond formation. Importantly, this additional step allows certain molecular catalysts to circumvent the "overpotential wall", leading to enhanced performance. With this knowledge, we establish fundamental principles for the design of ideal molecular OER catalysts.
Aggressive social interactions are used to compete for limited resources and are regulated by complex sensory cues and the organism's internal state. While both sexes exhibit aggression, its neuronal ...underpinnings are understudied in females. Here, we identify a population of sexually dimorphic aIPg neurons in the adult
central brain whose optogenetic activation increased, and genetic inactivation reduced, female aggression. Analysis of GAL4 lines identified in an unbiased screen for increased female chasing behavior revealed the involvement of another sexually dimorphic neuron, pC1d, and implicated aIPg and pC1d neurons as core nodes regulating female aggression. Connectomic analysis demonstrated that aIPg neurons and pC1d are interconnected and suggest that aIPg neurons may exert part of their effect by gating the flow of visual information to descending neurons. Our work reveals important regulatory components of the neuronal circuitry that underlies female aggressive social interactions and provides tools for their manipulation.
The behavioral response to a sensory stimulus may depend on both learned and innate neuronal representations. How these circuits interact to produce appropriate behavior is unknown. In Drosophila, ...the lateral horn (LH) and mushroom body (MB) are thought to mediate innate and learned olfactory behavior, respectively, although LH function has not been tested directly. Here we identify two LH cell types (PD2a1 and PD2b1) that receive input from an MB output neuron required for recall of aversive olfactory memories. These neurons are required for aversive memory retrieval and modulated by training. Connectomics data demonstrate that PD2a1 and PD2b1 neurons also receive direct input from food odor-encoding neurons. Consistent with this, PD2a1 and PD2b1 are also necessary for unlearned attraction to some odors, indicating that these neurons have a dual behavioral role. This provides a circuit mechanism by which learned and innate olfactory information can interact in identified neurons to produce appropriate behavior.
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•Specific Drosophila lateral horn neurons mediate innate attraction to food odors•The same neurons receive plastic odor information from the mushroom body•Recall after associative learning depends on reduced drive to lateral horn neurons•Connectomics circuit for integration of learned and innate odor representations
Sensory stimuli can engage both learned and innate behaviors. Dolan et al. identify neurons in Drosophila that directly integrate unlearned and plastic odor representations; they are required for innate approach to food odors but also learned aversive recall.
Efforts to map neural circuits have been galvanized by the development of genetic technologies that permit the manipulation of targeted sets of neurons in the brains of freely behaving animals. The ...success of these efforts relies on the experimenter's ability to target arbitrarily small subsets of neurons for manipulation, but such specificity of targeting cannot routinely be achieved using existing methods. In
, a widely-used technique for refined cell type-specific manipulation is the Split GAL4 system, which augments the targeting specificity of the binary GAL4-UAS (Upstream Activating Sequence) system by making GAL4 transcriptional activity contingent upon two enhancers, rather than one. To permit more refined targeting, we introduce here the "Killer Zipper" (KZip
), a suppressor that makes Split GAL4 targeting contingent upon a third enhancer. KZip
acts by disrupting both the formation and activity of Split GAL4 heterodimers, and we show how this added layer of control can be used to selectively remove unwanted cells from a Split GAL4 expression pattern or to subtract neurons of interest from a pattern to determine their requirement in generating a given phenotype. To facilitate application of the KZip
technology, we have developed a versatile set of LexA
-KZip
fly lines that can be used directly with the large number of LexA driver lines with known expression patterns. KZip
significantly sharpens the precision of neuronal genetic control available in
and may be extended to other organisms where Split GAL4-like systems are used.
To study radial peripapillary capillary (RPC) density in the early stages of diabetic retinopathy (DR), using optical coherence tomography angiography.
A cross-sectional evaluation of RPCs was ...performed using optical coherence tomography angiography (Avanti RTVue-XR 100, Optovue Inc, Fremont, CA). Annular RPC density was the primary outcome. Global density and retinal nerve fiber layer thickness were secondary outcomes. Diabetic eyes were divided into three groups: no DR, mild nonproliferative DR (mild NPDR), and moderate NPDR. Multilevel mixed-effects univariate and multivariate linear regression models were used.
We included 155 eyes (n = 42 control; n = 27 no DR; n = 28 mild NPDR; and n = 58 moderate NPDR) from 86 subjects (mean SD age 63.39 10.70 years; 46.45% male). When compared with controls, a significant decrease in annular RPC density was found in all groups of diabetic eyes on multivariate analysis (no DR: β = -2.95, P < 0.001; mild NPDR: β = -1.76, P = 0.017; and moderate NPDR: β = -2.82, P < 0.001). We also detected a significant decrease in retinal nerve fiber layer thickness in diabetic eyes (even in the no DR group). Furthermore, in diabetic eyes, annular RPC density and retinal nerve fiber layer thickness correlated significantly (R = 0.4874, P < 0.001).
Peripapillary neurovascular changes occur early in the course of DR. Their significance in the progression of DR warrants further research.
Microglia, the macrophages of the brain parenchyma, are key players in neurodegenerative diseases such as Alzheimer's disease. These cells adopt distinct transcriptional subtypes known as states. ...Understanding state function, especially in human microglia, has been elusive owing to a lack of tools to model and manipulate these cells. Here, we developed a platform for modeling human microglia transcriptional states in vitro. We found that exposure of human stem-cell-differentiated microglia to synaptosomes, myelin debris, apoptotic neurons or synthetic amyloid-beta fibrils generated transcriptional diversity that mapped to gene signatures identified in human brain microglia, including disease-associated microglia, a state enriched in neurodegenerative diseases. Using a new lentiviral approach, we demonstrated that the transcription factor MITF drives a disease-associated transcriptional signature and a highly phagocytic state. Together, these tools enable the manipulation and functional interrogation of human microglial states in both homeostatic and disease-relevant contexts.
Ultrafast tissue staining with chemical tags Kohl, Johannes; Ng, Julian; Cachero, Sebastian ...
Proceedings of the National Academy of Sciences - PNAS,
09/2014, Letnik:
111, Številka:
36
Journal Article
Recenzirano
Odprti dostop
Significance Cellular and subcellular structures in thick biological samples typically are visualized either by genetically encoded fluorescent proteins or by antibody staining against proteins of ...interest. However, both approaches have drawbacks. Fluorescent proteins do not survive treatments for tissue preservation well, are available in only a few colors, and often emit weak signals. Antibody stainings are slow, do not penetrate thick samples well, and often result in considerable background staining. We have overcome these limitations by using genetically encoded chemical tags that result in rapid, even staining of thick biological samples with high-signal and low-background labeling. We introduce tools for flies and mice that drastically improve the speed and specificity for labeling genetically marked cells in biological tissues.
Purpose
To evaluate the macular and peripapillary morpho-vascular changes in ADOA, using optical coherence tomography (OCT) and OCT angiography (OCTA).
Methods
Prospectively defined, cross-sectional ...case-control study. Consecutive patients with a genetic or clinical diagnosis of ADOA along with age- and sex-matched controls were included. The radial peripapillary capillary (RPC) density and vessel density (VD) in the parafoveal superficial and deep capillary plexuses (SCP and DCP, respectively) were evaluated with OCTA. The ganglion cell complex (GCC) and retinal nerve fiber layer (RNFL) thickness were determined using structural OCT. We applied a previously validated customized macro (Fiji, SciJava Consortium) to compute RPC density. The remaining parameters were calculated by the built-in software. Non-parametric methods were used for data analysis. The target α level was 0.05, which was adjusted through Bonferroni’s correction when multiple outcomes were tested.
Results
Fifty-eight eyes (
n
= 29 control;
n
= 29 ADOA) from 30 subjects (mean age 42.43 ± 15.30 years; 37.93% male) were included. Parafoveal SCP VD, GCC thickness, RPC VD in the temporal quadrant, as well as RNFL thickness in the nasal and temporal quadrants were decreased in ADOA eyes (all
p
< 0.001). When only patients with genetically confirmed diagnosis were included, capillary dropout in the circumpapillary superior and inferior quadrants also became evident (both
p
< 0.001). The GCC/parafoveal SCP ratio was increased in ADOA, relatively to matched controls. In contrast, none of the circumpapillary morpho-vascular ratios was significantly different in ADOA eyes.
Conclusions
The microvascular and structural changes found in ADOA suggest that both the macular and peripapillary regions are involved, although the threshold for damage of the structural and vascular components may be different for each region. Larger series with longitudinal follow-up may validate OCTA biomarkers helpful for disease monitoring.
The same sensory signal can be interpreted differently according to context. A new study in Drosophila uses cell-type-specific tools to identify neural circuits that integrate context during ...olfactory processing and surprisingly implicates memory-recall neurons.
The same sensory signal can be interpreted differently according to context. A new study in Drosophila uses cell-type specific tools to identify neural circuits that integrate context during olfactory processing and surprisingly implicates memory-recall neurons.
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