scholarly journals Plume dynamics structure the spatiotemporal activity of glomerular networks in the mouse olfactory bulb

2020 ◽  
Author(s):  
Suzanne M. Lewis ◽  
Lai Xu ◽  
Nicola Rigolli ◽  
Mohammad F. Tariq ◽  
Merav Stern ◽  
...  
Keyword(s):  
Olfactory Bulb ◽  
Olfactory System ◽  
Large Scale ◽  
Early Stage ◽  
Wide Field ◽  
Flow Conditions ◽  
Population Activity ◽  
Plume Dynamics ◽  
Olfactory Glomeruli ◽  
Odor Plumes

AbstractAlthough mice locate resources using turbulent airborne odor plumes, the stochasticity and intermittency of fluctuating plumes create challenges for interpreting odor cues in natural environments. Population activity within the olfactory bulb (OB), is thought to process this complex spatial and temporal information, but how plume dynamics impact odor representation in this early stage of the mouse olfactory system is not known. Limitations in odor detection technology have made it impossible to measure plume fluctuations while simultaneously recording from the mouse’s brain. Thus, previous studies have measured OB activity following controlled odor pulses of varying profiles or frequencies, but this approach only captures a subset of features found within olfactory plumes. Adequately sampling this feature space is difficult given a lack of knowledge regarding which features the brain extracts during exposure to natural olfactory scenes. Here we measured OB responses to naturally fluctuating odor plumes using a miniature, adapted odor sensor combined with wide-field GCaMP6f signaling from the dendrites of mitral and tufted (MT) cells imaged in olfactory glomeruli of head-fixed mice. We precisely tracked plume dynamics and imaged glomerular responses to this fluctuating input, while varying flow conditions across a range of ethologically-relevant values. We found that a consistent portion of MT activity in glomeruli follows odor concentration dynamics, and the strongest responding glomeruli are the best at following fluctuations within odor plumes. Further, the reliability and average response magnitude of glomerular populations of MT cells are affected by the flow condition in which the animal samples the plume, with the fidelity of plume following by MT cells increasing in conditions of higher flow velocity where odor dynamics result in intermittent whiffs of stronger concentration. Thus, the flow environment in which an animal encounters an odor has a large-scale impact on the temporal representation of an odor plume in the OB. Additionally, across flow conditions odor dynamics are a major driver of activity in many glomerular networks. Taken together, these data demonstrate that plume dynamics structure olfactory representations in the first stage of odor processing in the mouse olfactory system.

scholarly journals Plume Dynamics Structure the Spatiotemporal Activity of Mitral/Tufted Cell Networks in the Mouse Olfactory Bulb

2021 ◽  
Vol 15 ◽  
Author(s):  
Suzanne M. Lewis ◽  
Lai Xu ◽  
Nicola Rigolli ◽  
Mohammad F. Tariq ◽  
Lucas M. Suarez ◽  
...  
Keyword(s):  
Olfactory Bulb ◽  
Olfactory System ◽  
Large Scale ◽  
Early Stage ◽  
Wide Field ◽  
Flow Conditions ◽  
Population Activity ◽  
Plume Dynamics ◽  
Olfactory Glomeruli ◽  
Odor Plumes

Although mice locate resources using turbulent airborne odor plumes, the stochasticity and intermittency of fluctuating plumes create challenges for interpreting odor cues in natural environments. Population activity within the olfactory bulb (OB) is thought to process this complex spatial and temporal information, but how plume dynamics impact odor representation in this early stage of the mouse olfactory system is unknown. Limitations in odor detection technology have made it difficult to measure plume fluctuations while simultaneously recording from the mouse's brain. Thus, previous studies have measured OB activity following controlled odor pulses of varying profiles or frequencies, but this approach only captures a subset of features found within olfactory plumes. Adequately sampling this feature space is difficult given a lack of knowledge regarding which features the brain extracts during exposure to natural olfactory scenes. Here we measured OB responses to naturally fluctuating odor plumes using a miniature, adapted odor sensor combined with wide-field GCaMP6f signaling from the dendrites of mitral and tufted (MT) cells imaged in olfactory glomeruli of head-fixed mice. We precisely tracked plume dynamics and imaged glomerular responses to this fluctuating input, while varying flow conditions across a range of ethologically-relevant values. We found that a consistent portion of MT activity in glomeruli follows odor concentration dynamics, and the strongest responding glomeruli are the best at following fluctuations within odor plumes. Further, the reliability and average response magnitude of glomerular populations of MT cells are affected by the flow condition in which the animal samples the plume, with the fidelity of plume following by MT cells increasing in conditions of higher flow velocity where odor dynamics result in intermittent whiffs of stronger concentration. Thus, the flow environment in which an animal encounters an odor has a large-scale impact on the temporal representation of an odor plume in the OB. Additionally, across flow conditions odor dynamics are a major driver of activity in many glomerular networks. Taken together, these data demonstrate that plume dynamics structure olfactory representations in the first stage of odor processing in the mouse olfactory system.

scholarly journals Changes in weak pair-wise correlations during running reshapes network state in the main olfactory bulb

2020 ◽  
Author(s):  
Udaysankar Chockanathan ◽  
Emily J. W. Crosier ◽  
Spencer Waddle ◽  
Edward Lyman ◽  
Richard C. Gerkin ◽  
...  
Keyword(s):  
Olfactory Bulb ◽  
Spontaneous Activity ◽  
Olfactory System ◽  
Activity Patterns ◽  
Higher Order ◽  
High Density ◽  
Main Olfactory Bulb ◽  
Population Activity ◽  
Maximum Entropy Models ◽  
Electrophysiological Recordings

AbstractNeural codes for sensory representations are thought to reside in a broader space defined by the patterns of spontaneous activity that occur when stimuli are not being presented. To understand the structure of this spontaneous activity in the olfactory system, we performed high-density recordings of population activity in the main olfactory bulb of awake mice. We found that spontaneous activity patterns of ensembles of mitral and tufted (M/T) cells in the main olfactory bulb changed dramatically during locomotion, including decreases in pairwise correlations between neurons and increases in the entropy of the population. Maximum entropy models of the ensemble activity revealed that pair-wise interactions were better at predicting patterns of activity when the animal was stationary than while running, suggesting that higher order (3rd, 4th order) interactions between neurons shape activity during locomotion. Taken together, we found that locomotion influenced the structure of spontaneous population activity at the earliest stages of olfactory processing, 1 synapse away from the sensory receptors in the nasal epithelium.New and NoteworthyThe organization and structure of spontaneous population activity in the olfactory system places constraints of how odor information is represented. Using high-density electrophysiological recordings of mitral and tufted cells, we found that running increases the dimensionality of spontaneous activity, implicating higher-order interactions among neurons during locomotion. Behavior thus flexibly alters neuronal activity at the earliest stages of sensory processing.

scholarly journals Changes in pairwise correlations during running reshape global network state in the main olfactory bulb

2021 ◽  
Vol 125 (5) ◽  
pp. 1612-1623
Author(s):  
Udaysankar Chockanathan ◽  
Emily J. W. Crosier ◽  
Spencer Waddle ◽  
Edward Lyman ◽  
Richard C. Gerkin ◽  
...  
Keyword(s):  
Olfactory Bulb ◽  
Sensory Processing ◽  
Olfactory System ◽  
Global Network ◽  
Main Olfactory Bulb ◽  
Population Activity ◽  
Network State ◽  
Electrophysiological Recordings ◽  
Pairwise Correlations ◽  
Locomotion Behavior

The organization and structure of spontaneous population activity in the olfactory system places constraints of how odor information is represented. Using high-density electrophysiological recordings of mitral and tufted cells, we found that running increases the dimensionality of spontaneous activity, implicating higher order interactions among neurons during locomotion. Behavior, thus, flexibly alters neuronal activity at the earliest stages of sensory processing.

Konkurrenz zwischen Stieleiche und Buche auf Lothar-Sturmflächen | Competition between pedunculate oak and European beech on Lothar windthrow areas

2009 ◽  
Vol 160 (5) ◽  
pp. 114-123 ◽  
Author(s):  
Daniel Otto ◽  
Sven Wagner ◽  
Peter Brang
Keyword(s):  
Large Scale ◽  
Early Stage ◽  
Tree Height ◽  
European Beech ◽  
Threshold Value ◽  
Test Methods ◽  
Permanent Plots ◽  
Pedunculate Oak ◽  
Competitive Pressure ◽  
Competition Index

The competitive pressure of naturally regenerated European beech (Fagus sylvatica) saplings on planted pedunculate oak (Quercus robur) was investigated on two 1.8 ha permanent plots near Habsburg and Murten (Switzerland). The plots were established with the aim to test methods of artificial oak regeneration after large-scale windthrow. On both plots, 80 oaks exposed to varying levels of competitive pressure from at most 10 neighbouring beech trees were selected. The height of each oak as well as stem and branch diameters were measured. The competitive pressure was assessed using Schütz's competition index, which is based on relative tree height, crown overlap and distance from competing neighbours. Oak trees growing without or with only slight competition from beech were equally tall, while oaks exposed to moderate to strong competition were smaller. A threshold value for the competition index was found above which oak height decreased strongly. The stem and branch diameters of the oaks started to decrease even if the competition from beech was slight, and decreased much further with more competition. The oak stems started to become more slender even with only slight competition from beech. On the moderately acid beech sites studied here, beech grow taller faster than oak. Thus where beech is competing with oak and the aim is to maintain the oak, competitive pressure on the oak must be reduced at an early stage. The degree of the intervention should, however, take the individual competitive interaction into account, with more intervention if the competition is strong.

scholarly journals Extinction reverses olfactory fear-conditioned increases in neuron number and glomerular size

2015 ◽  
Vol 112 (41) ◽  
pp. 12846-12851 ◽  
Author(s):  
Filomene G. Morrison ◽  
Brian G. Dias ◽  
Kerry J. Ressler
Keyword(s):  
Olfactory Bulb ◽  
Learning And Memory ◽  
Olfactory Epithelium ◽  
Olfactory System ◽  
Structural Changes ◽  
Freezing Behavior ◽  
Extinction Training ◽  
Odor Stimulus ◽  
Main Olfactory Epithelium ◽  
Odor Learning

Although much work has investigated the contribution of brain regions such as the amygdala, hippocampus, and prefrontal cortex to the processing of fear learning and memory, fewer studies have examined the role of sensory systems, in particular the olfactory system, in the detection and perception of cues involved in learning and memory. The primary sensory receptive field maps of the olfactory system are exquisitely organized and respond dynamically to cues in the environment, remaining plastic from development through adulthood. We have previously demonstrated that olfactory fear conditioning leads to increased odorant-specific receptor representation in the main olfactory epithelium and in glomeruli within the olfactory bulb. We now demonstrate that olfactory extinction training specific to the conditioned odor stimulus reverses the conditioning-associated freezing behavior and odor learning-induced structural changes in the olfactory epithelium and olfactory bulb in an odorant ligand-specific manner. These data suggest that learning-induced freezing behavior, structural alterations, and enhanced neural sensory representation can be reversed in adult mice following extinction training.

scholarly journals Region-specific amyloid-β accumulation in the olfactory system influences olfactory sensory neuronal dysfunction in 5xFAD mice

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Gowoon Son ◽  
Seung-Jun Yoo ◽  
Shinwoo Kang ◽  
Ameer Rasheed ◽  
Da Hae Jung ◽  
...  
Keyword(s):  
Olfactory Bulb ◽  
Sensory Neurons ◽  
Olfactory System ◽  
Amyloid Β ◽  
Olfactory Sensory Neurons ◽  
Basal Cells ◽  
Irreversible Damage ◽  
5Xfad Mouse ◽  
Peripheral Areas ◽  
5Xfad Mice

Abstract Background Hyposmia in Alzheimer’s disease (AD) is a typical early symptom according to numerous previous clinical studies. Although amyloid-β (Aβ), which is one of the toxic factors upregulated early in AD, has been identified in many studies, even in the peripheral areas of the olfactory system, the pathology involving olfactory sensory neurons (OSNs) remains poorly understood. Methods Here, we focused on peripheral olfactory sensory neurons (OSNs) and delved deeper into the direct relationship between pathophysiological and behavioral results using odorants. We also confirmed histologically the pathological changes in 3-month-old 5xFAD mouse models, which recapitulates AD pathology. We introduced a numeric scale histologically to compare physiological phenomenon and local tissue lesions regardless of the anatomical plane. Results We observed the odorant group that the 5xFAD mice showed reduced responses to odorants. These also did not physiologically activate OSNs that propagate their axons to the ventral olfactory bulb. Interestingly, the amount of accumulated amyloid-β (Aβ) was high in the OSNs located in the olfactory epithelial ectoturbinate and the ventral olfactory bulb glomeruli. We also observed irreversible damage to the ectoturbinate of the olfactory epithelium by measuring the impaired neuronal turnover ratio from the basal cells to the matured OSNs. Conclusions Our results showed that partial and asymmetrical accumulation of Aβ coincided with physiologically and structurally damaged areas in the peripheral olfactory system, which evoked hyporeactivity to some odorants. Taken together, partial olfactory dysfunction closely associated with peripheral OSN’s loss could be a leading cause of AD-related hyposmia, a characteristic of early AD.

scholarly journals Favorable Effects of GLP-1 Receptor Agonist against Pancreatic β-Cell Glucose Toxicity and the Development of Arteriosclerosis: “The Earlier, the Better” in Therapy with Incretin-Based Medicine

2021 ◽  
Vol 22 (15) ◽  
pp. 7917
Author(s):  
Hideaki Kaneto ◽  
Tomohiko Kimura ◽  
Masashi Shimoda ◽  
Atsushi Obata ◽  
Junpei Sanada ◽  
...  
Keyword(s):  
Large Scale ◽  
Cell Function ◽  
Apoptotic Cell ◽  
Early Stage ◽  
Insulin Biosynthesis ◽  
Protective Effects ◽  
Pancreatic Β Cell ◽  
Β Cells ◽  
Β Cell ◽  
Glucose Toxicity

Fundamental pancreatic β-cell function is to produce and secrete insulin in response to blood glucose levels. However, when β-cells are chronically exposed to hyperglycemia in type 2 diabetes mellitus (T2DM), insulin biosynthesis and secretion are decreased together with reduced expression of insulin transcription factors. Glucagon-like peptide-1 (GLP-1) plays a crucial role in pancreatic β-cells; GLP-1 binds to the GLP-1 receptor (GLP-1R) in the β-cell membrane and thereby enhances insulin secretion, suppresses apoptotic cell death and increase proliferation of β-cells. However, GLP-1R expression in β-cells is reduced under diabetic conditions and thus the GLP-1R activator (GLP-1RA) shows more favorable effects on β-cells at an early stage of T2DM compared to an advanced stage. On the other hand, it has been drawing much attention to the idea that GLP-1 signaling is important in arterial cells; GLP-1 increases nitric oxide, which leads to facilitation of vascular relaxation and suppression of arteriosclerosis. However, GLP-1R expression in arterial cells is also reduced under diabetic conditions and thus GLP-1RA shows more protective effects on arteriosclerosis at an early stage of T2DM. Furthermore, it has been reported recently that administration of GLP-1RA leads to the reduction of cardiovascular events in various large-scale clinical trials. Therefore, we think that it would be better to start GLP-1RA at an early stage of T2DM for the prevention of arteriosclerosis and protection of β-cells against glucose toxicity in routine medical care.

scholarly journals Understanding the Processes Causing the Early Intensification of Hurricane Dorian through an Ensemble of the Hurricane Analysis and Forecast System (HAFS)

Atmosphere ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 93
Author(s):  
Andrew Hazelton ◽  
Ghassan J. Alaka ◽  
Levi Cowan ◽  
Michael Fischer ◽  
Sundararaman Gopalakrishnan
Keyword(s):  
Tropical Cyclone ◽  
Large Scale ◽  
Early Stage ◽  
Early Period ◽  
Storm Track ◽  
Key Factors ◽  
Complex Interplay ◽  
Forecast System ◽  
Model Initialization

The early stages of a tropical cyclone can be a challenge to forecast, as a storm consolidates and begins to grow based on the local and environmental conditions. A high-resolution ensemble of the Hurricane Analysis and Forecast System (HAFS) is used to study the early intensification of Hurricane Dorian, a catastrophic 2019 storm in which the early period proved challenging for forecasters. There was a clear connection in the ensemble between early storm track and intensity: stronger members moved more northeast initially, although this result did not have much impact on the long-term track. The ensemble results show several key factors determining the early evolution of Dorian. Large-scale divergence northeast of the tropical cyclone (TC) appeared to favor intensification, and this structure was present at model initialization. There was also greater moisture northeast of the TC for stronger members at initialization, favoring more intensification and downshear development of the circulation as these members evolved. This study highlights the complex interplay between synoptic and storm scale processes in the development and intensification of early-stage tropical cyclones.

scholarly journals Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening

2019 ◽  
Vol 25 (1) ◽  
pp. 9-20 ◽  
Author(s):  
Olivia W. Lee ◽  
Shelley Austin ◽  
Madison Gamma ◽  
Dorian M. Cheff ◽  
Tobie D. Lee ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
High Throughput ◽  
High Throughput Screening ◽  
Drug Targets ◽  
Large Scale ◽  
Early Stage ◽  
Cancer Cell Line ◽  
Hek 293 ◽  
Cytotoxic Compounds

Cell-based phenotypic screening is a commonly used approach to discover biological pathways, novel drug targets, chemical probes, and high-quality hit-to-lead molecules. Many hits identified from high-throughput screening campaigns are ruled out through a series of follow-up potency, selectivity/specificity, and cytotoxicity assays. Prioritization of molecules with little or no cytotoxicity for downstream evaluation can influence the future direction of projects, so cytotoxicity profiling of screening libraries at an early stage is essential for increasing the likelihood of candidate success. In this study, we assessed the cell-based cytotoxicity of nearly 10,000 compounds in the National Institutes of Health, National Center for Advancing Translational Sciences annotated libraries and more than 100,000 compounds in a diversity library against four normal cell lines (HEK 293, NIH 3T3, CRL-7250, and HaCat) and one cancer cell line (KB 3-1, a HeLa subline). This large-scale library profiling was analyzed for overall screening outcomes, hit rates, pan-activity, and selectivity. For the annotated library, we also examined the primary targets and mechanistic pathways regularly associated with cell death. To our knowledge, this is the first study to use high-throughput screening to profile a large screening collection (>100,000 compounds) for cytotoxicity in both normal and cancer cell lines. The results generated here constitute a valuable resource for the scientific community and provide insight into the extent of cytotoxic compounds in screening libraries, allowing for the identification and avoidance of compounds with cytotoxicity during high-throughput screening campaigns.

Sign in / Sign up

Export Citation Format

Share Document