scholarly journals Obesity remodels activity and transcriptional state of a lateral hypothalamic brake on feeding

Science ◽  
2019 ◽  
Vol 364 (6447) ◽  
pp. 1271-1274 ◽  
Author(s):  
Mark A. Rossi ◽  
Marcus L. Basiri ◽  
Jenna A. McHenry ◽  
Oksana Kosyk ◽  
James M. Otis ◽  
...  
Keyword(s):  
Energy Homeostasis ◽  
Health Concern ◽  
Hypothalamic Area ◽  
Obesity Epidemic ◽  
Glutamatergic Neurons ◽  
Two Photon ◽  
Lateral Hypothalamic ◽  
The Brain ◽  
Transcriptional State

The current obesity epidemic is a major worldwide health concern. Despite the consensus that the brain regulates energy homeostasis, the neural adaptations governing obesity are unknown. Using a combination of high-throughput single-cell RNA sequencing and longitudinal in vivo two-photon calcium imaging, we surveyed functional alterations of the lateral hypothalamic area (LHA)—a highly conserved brain region that orchestrates feeding—in a mouse model of obesity. The transcriptional profile of LHA glutamatergic neurons was affected by obesity, exhibiting changes indicative of altered neuronal activity. Encoding properties of individual LHA glutamatergic neurons were then tracked throughout obesity, revealing greatly attenuated reward responses. These data demonstrate how diet disrupts the function of an endogenous feeding suppression system to promote overeating and obesity.

scholarly journals P02.08 Visualizing tumor cell - lymphocyte interactions in the brain metastatic cascade using in vivo two photon microscopy

2018 ◽  
Vol 20 (suppl_3) ◽  
pp. iii273-iii273
Author(s):  
M Piechutta ◽  
A S Berghoff ◽  
M A Karreman ◽  
K Gunkel ◽  
W Wick ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Metastatic Cascade ◽  
Two Photon Microscopy ◽  
Two Photon ◽  
The Brain

scholarly journals Widespread inhibition, antagonism, and synergy in mouse olfactory sensory neurons in vivo

2019 ◽  
Author(s):  
Shigenori Inagaki ◽  
Ryo Iwata ◽  
Masakazu Iwamoto ◽  
Takeshi Imai
Keyword(s):  
Sensory Neurons ◽  
Calcium Imaging ◽  
Odorant Receptor ◽  
Sensory Information ◽  
Olfactory Sensory Neurons ◽  
Axon Terminals ◽  
Two Photon ◽  
Odor Mixtures ◽  
The Brain

SUMMARYSensory information is selectively or non-selectively inhibited and enhanced in the brain, but it remains unclear whether this occurs commonly at the peripheral stage. Here, we performed two-photon calcium imaging of mouse olfactory sensory neurons (OSNs) in vivo and found that odors produce not only excitatory but also inhibitory responses at their axon terminals. The inhibitory responses remained in mutant mice, in which all possible sources of presynaptic lateral inhibition were eliminated. Direct imaging of the olfactory epithelium revealed widespread inhibitory responses at OSN somata. The inhibition was in part due to inverse agonism toward the odorant receptor. We also found that responses to odor mixtures are often suppressed or enhanced in OSNs: Antagonism was dominant at higher odor concentrations, whereas synergy was more prominent at lower odor concentrations. Thus, odor responses are extensively tuned by inhibition, antagonism, and synergy, at the early peripheral stage, contributing to robust odor representations.

scholarly journals Microglia motility depends on neuronal activity and promotes structural plasticity in the hippocampus

2019 ◽  
Author(s):  
Felix C. Nebeling ◽  
Stefanie Poll ◽  
Lena C. Schmid ◽  
Manuel Mittag ◽  
Julia Steffen ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Dendritic Spines ◽  
Synapse Formation ◽  
Brain Parenchyma ◽  
Two Photon ◽  
Contact Rates ◽  
Health And Disease ◽  
The Impact ◽  
The Brain

AbstractMicroglia, the resident immune cells of the brain, play a complex role in health and disease. They actively survey the brain parenchyma by physically interacting with other cells and structurally shaping the brain. Yet, the mechanisms underlying microglia motility and their significance for synapse stability, especially during adulthood, remain widely unresolved. Here we investigated the impact of neuronal activity on microglia motility and its implication for synapse formation and survival. We used repetitive two-photon in vivo imaging in the hippocampus of awake mice to simultaneously study microglia motility and their interaction with synapses. We found that microglia process motility depended on neuronal activity. Simultaneously, more dendritic spines emerged in awake compared to anesthetized mice. Interestingly, microglia contact rates with individual dendritic spines were associated with their stability. These results suggest that microglia are not only sensing neuronal activity, but participate in synaptic rewiring of the hippocampus during adulthood, which has profound relevance for learning and memory processes.

scholarly journals Efficient implementation of convolutional neural networks in the data processing of two-photon in vivo imaging

2019 ◽  
Vol 35 (17) ◽  
pp. 3208-3210 ◽  
Author(s):  
Yangzhen Wang ◽  
Feng Su ◽  
Shanshan Wang ◽  
Chaojuan Yang ◽  
Yonglu Tian ◽  
...  
Keyword(s):  
Neural Networks ◽  
Convolutional Neural Networks ◽  
Detection Methods ◽  
Supplementary Information ◽  
Imaging Data ◽  
Two Photon ◽  
Processing Power ◽  
Fluctuation Method ◽  
The Brain

Abstract Motivation Functional imaging at single-neuron resolution offers a highly efficient tool for studying the functional connectomics in the brain. However, mainstream neuron-detection methods focus on either the morphologies or activities of neurons, which may lead to the extraction of incomplete information and which may heavily rely on the experience of the experimenters. Results We developed a convolutional neural networks and fluctuation method-based toolbox (ImageCN) to increase the processing power of calcium imaging data. To evaluate the performance of ImageCN, nine different imaging datasets were recorded from awake mouse brains. ImageCN demonstrated superior neuron-detection performance when compared with other algorithms. Furthermore, ImageCN does not require sophisticated training for users. Availability and implementation ImageCN is implemented in MATLAB. The source code and documentation are available at https://github.com/ZhangChenLab/ImageCN. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals IMMU-26. VISUALIZING TUMOR CELL - LYMPHOCYTE INTERACTIONS IN THE BRAIN METASTATIC CASCADE USING IN VIVO TWO PHOTON MICROSCOPY

2018 ◽  
Vol 20 (suppl_6) ◽  
pp. vi126-vi127
Author(s):  
Manuel Piechutta ◽  
Anna Berghoff ◽  
Matthia Karreman ◽  
Katharina Gunkel ◽  
Wolfgang Wick ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Metastatic Cascade ◽  
Two Photon Microscopy ◽  
Two Photon ◽  
The Brain

The role of amylin in the control of energy homeostasis

2010 ◽  
Vol 298 (6) ◽  
pp. R1475-R1484 ◽  
Author(s):  
Thomas A. Lutz
Keyword(s):  
Energy Homeostasis ◽  
Area Postrema ◽  
Body Weight Gain ◽  
Direct Action ◽  
Central Administration ◽  
Experimental Conditions ◽  
Hypothalamic Area ◽  
Chronic Infusion ◽  
The Brain

Amylin is an important player in the control of nutrient fluxes. Amylin reduces eating via a meal size effect by promoting meal-ending satiation. This effect seems to depend on a direct action in the area postrema (AP), which is an area rich in amylin receptors. Subsequent to the activation of AP neurons, the neural signal is conveyed to the forebrain via relays involving the nucleus of the solitary tract (NTS) and the lateral parabrachial nucleus (lPBN) to the lateral hypothalamic area (LHA) and other hypothalamic nuclei. While the NTS and lPBN seem to be necessary for amylin's eating inhibitory effect, the role of the LHA has not yet been fully investigated. Amylin may also act as an adiposity signal. Plasma levels of amylin are higher in obese individuals, and chronic infusion of amylin into the brain reduces body weight gain and adiposity; chronic infusion of an amylin receptor antagonist into the brain increases body adiposity. Amylin increases energy expenditure in rats; this effect occurs under various experimental conditions after peripheral and central administration. Together, these animal data, but also clinical data in humans, indicate that amylin is a promising candidate for the treatment of obesity; effects are most pronounced when amylin is combined with leptin. Finally, recent findings indicate that amylin acts as a neurotrophic factor in specific brain stem areas. Whether this effect may be relevant under physiological conditions requires further studies.

scholarly journals Post-capillary venules is the locus for transcytosis of therapeutic nanoparticles to the brain

2020 ◽  
Author(s):  
Krzysztof Kucharz ◽  
Kasper Kristensen ◽  
Kasper Bendix Johnsen ◽  
Mette Aagaard Lund ◽  
Micael Lønstrup ◽  
...  
Keyword(s):  
Drug Carrier ◽  
Basement Membranes ◽  
List Type ◽  
Biologic Drugs ◽  
Large Molecules ◽  
Two Photon Microscopy ◽  
Two Photon ◽  
Resolution Imaging ◽  
The Brain

SUMMARYTreatments of neurodegenerative diseases require biologic drugs to be actively transported across the blood-brain barrier (BBB). To answer outstanding questions regarding transport mechanisms, we determined how and where transcytosis occurs at the BBB. Using two-photon microscopy, we characterized the transport of therapeutic nanoparticles at all steps of delivery to the brain and at the nanoscale resolution in vivo. Transferrin receptor-targeted nanoparticles were taken up by endothelium at capillaries and venules, but not at arterioles. The nanoparticles moved unobstructed within endothelial cells, but transcytosis across the BBB occurred only at post-capillary venules, where endothelial and glial basement membranes form a perivascular space that can accommodate biologics. In comparison, transcytosis was absent in capillaries with closely apposed basement membranes. Thus, post-capillary venules, not capillaries, provide an entry point for transport of large molecules across the BBB, and targeting therapeutic agents to this locus may be an effective way for treating brain disorders.HIGHLIGHTSIntegration of drug carrier nanotechnology with two-photon microscopy in vivoReal-time nanoscale-resolution imaging of nanoparticle transcytosis to the brainDistinct trafficking pattern in the endothelium of cerebral venules and capillariesVenules, not capillaries, is the locus for brain uptake of therapeutic nanoparticles

scholarly journals Multi-functional feedforward inhibitory circuits for cortical odor processing

2021 ◽  
Author(s):  
Norimitsu Suzuki ◽  
Malinda L. S. Tantirigama ◽  
Helena H.-Y. Huang ◽  
John M. Bekkers
Keyword(s):  
Calcium Imaging ◽  
Piriform Cortex ◽  
Complex Interplay ◽  
Inhibitory Circuits ◽  
Two Photon ◽  
Odor Processing ◽  
Strong Excitation ◽  
The Brain ◽  
Feedforward Inhibition

Feedforward inhibitory circuits are key contributors to the complex interplay between excitation and inhibition in the brain. Little is known about the function of feedforward inhibition in the primary olfactory (piriform) cortex. Using in vivo two-photon targeted patch clamping and calcium imaging in mice, we find that odors evoke strong excitation in two classes of interneurons – neurogliaform (NG) cells and horizontal (HZ) cells – that provide feedforward inhibition in layer 1 of the piriform cortex. NG cells fire much earlier than HZ cells following odor onset, a difference that can be attributed to the faster odor-driven excitatory synaptic drive that NG cells receive from the olfactory bulb. As a consequence, NG cells strongly but transiently inhibit odor-evoked excitation in layer 2 principal cells, whereas HZ cells provide more diffuse and prolonged feedforward inhibition. Our findings reveal unexpected complexity in the operation of inhibition in the piriform cortex.

scholarly journals In vivo imaging of the kinetics of microglial self-renewal and maturation in the adult visual cortex

2020 ◽  
Author(s):  
Monique S. Mendes ◽  
Jason Atlas ◽  
Zachary Brehm ◽  
Antonio Ladron-de-Guevara ◽  
Matthew N. McCall ◽  
...  
Keyword(s):  
Mathematical Model ◽  
Visual Cortex ◽  
Adult Brain ◽  
Self Renewal ◽  
Two Photon ◽  
And Migration ◽  
The Mathematical Model ◽  
Kinetics Of ◽  
The Brain

AbstractMicroglia are the resident immune cells in the brain with the capacity to autonomously self-renew. Under basal conditions, microglial self-renewal appears to be slow and stochastic, although microglia have the ability to proliferate very rapidly following depletion or in response to injury. Because microglial self-renewal has largely been studied using static tools, the mechanisms and kinetics by which microglia renew and acquire mature characteristics in the adult brain are not well understood. Using chronic in vivo two-photon imaging in awake mice and PLX5622 (Colony stimulating factor 1 receptor (CSF1R) inhibitor) to deplete microglia, we set out to understand the dynamic self-organization and maturation of microglia following depletion in the visual cortex. We confirm that under basal conditions, cortical microglia show limited turnover and migration. Following depletion, however, microglial repopulation is remarkably rapid and is sustained by the dynamic division of the remaining microglia in a manner that is largely independent of signaling through the P2Y12 receptor. Mathematical modeling of microglial division demonstrates that the observed division rates can account for the rapid repopulation observed in vivo. Additionally, newly-born microglia resemble mature microglia, in terms of their morphology, dynamics and ability to respond to injury, within days of repopulation. Our work suggests that microglia rapidly self-renew locally, without the involvement of a special progenitor cell, and that newly born microglia do not recapitulate a slow developmental maturation but instead quickly take on mature roles in the nervous system.Graphical Abstract(a) Microglial dynamics during control condition. Cartoon depiction of the heterogenous microglia in the visual cortex equally spaced. (b) During the early stages of repopulation, microglia are irregularly spaced and sparse. (c) During the later stages of repopulation, the number of microglia and the spatial distribution return to baseline. (d-f) We then created and ran a mathematical model that sampled the number of microglia, (d) the persistent doublets, (e) the rapid divisions of microglia and (f) the secondary divisions of microglia during the peak of repopulation day 2-day 3. The mathematical model suggested that residual microglia can account for the rapid repopulation we observed in vivo.

Abstract 66: No Evidence of Functional Peri-Infarct Circuit Remapping in Mouse Somatosensory Cortex After Ischemic Stroke

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
William Zeiger ◽  
Mate Marosi ◽  
Satvir Saggi ◽  
Natalie Noble ◽  
Isa Samad ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Somatosensory Cortex ◽  
Single Neuron ◽  
Direct Evidence ◽  
Individual Layer ◽  
Two Photon ◽  
Whisker Stimulation ◽  
Transcriptomic Changes ◽  
The Brain

Following ischemic stroke, many patients exhibit partial spontaneous recovery, suggesting that the brain has endogenous mechanisms to recover lost functions. Evidence supports a role for peri-infarct cortex in recovery as this area undergoes structural, physiologic, and transcriptomic changes following stroke. It has been hypothesized that these changes promote circuit rewiring, leading spared neurons in the peri-infarct cortex to “remap” and subsume the function previously performed by neurons in the ischemic core. However, direct evidence for remapping at the single neuron level is lacking. To test this, we targeted photothrombotic (PT) strokes to an individual barrel (C1) in the barrel field of mouse primary somatosensory cortex (S1BF). We then performed longitudinal in vivo two-photon (2P) calcium imaging in Thy1 -GCaMP6s transgenic mice and recorded whisker-evoked responses of individual layer 2/3 neurons in the adjacent D3 barrel. Before stroke, ~30% of active neurons in the D3 barrel respond to stimulation of the D3 whisker and ~8% of neurons respond to the C1 whisker. Based on the remapping hypothesis, we predicted that the percentage of C1 whisker-responsive neurons in the spared D3 barrel would increase after stroke; however, we found that only ~2% of neurons in the D3 barrel responded to C1 whisker stimulation one month after stroke. We also tested the effect of forced-use therapy on recovery by plucking all whiskers, except the C1 whisker corresponding to the infarcted barrel, following stroke. Still, we found that forced-use therapy did not lead to an increased percentage of C1 whisker-responsive neurons, but it did enhance the responses to C1 whisker stimulation in surviving C1-responsive neurons in the peri-infarct cortex. These results suggest that at the circuit level recovery may occur through potentiation of spared homotopic neurons rather than remapping of neurons to perform new functions.

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