scholarly journals Heterogeneous effects of norepinephrine on spontaneous and stimulus-driven activity in the male accessory olfactory bulb

2017 ◽  
Vol 117 (3) ◽  
pp. 1342-1351 ◽  
Author(s):  
Wayne I. Doyle ◽  
Julian P. Meeks
Keyword(s):  
Information Processing ◽  
Olfactory Bulb ◽  
Spontaneous Activity ◽  
Behavioral Plasticity ◽  
Ex Vivo ◽  
Model Systems ◽  
Projection Neurons ◽  
Response Suppression ◽  
Accessory Olfactory Bulb ◽  
The Impact

Norepinephrine (NE) release has been linked to experience-dependent plasticity in many model systems and brain regions. Among these is the rodent accessory olfactory system (AOS), which is crucial for detecting and processing socially relevant environmental cues. The accessory olfactory bulb (AOB), the first site of chemosensory information processing in the AOS, receives dense centrifugal innervation by noradrenergic fibers originating in the locus coeruleus. Although NE release has been linked to behavioral plasticity through its actions in the AOB, the impacts of noradrenergic modulation on AOB information processing have not been thoroughly studied. We made extracellular single-unit recordings of AOB principal neurons in ex vivo preparations of the early AOS taken from adult male mice. We analyzed the impacts of bath-applied NE (10 μM) on spontaneous and stimulus-driven activity. In the presence of NE, we observed overall suppression of stimulus-driven neuronal activity with limited impact on spontaneous activity. NE-associated response suppression in the AOB came in two forms: one that was strong and immediate (21%) and one other that involved gradual, stimulus-dependent monotonic response suppression (47%). NE-associated changes in spontaneous activity were more modest, with an overall increase in spontaneous spike frequency observed in 25% of neurons. Neurons with increased spontaneous activity demonstrated a net decrease in chemosensory discriminability. These results reveal that noradrenergic signaling in the AOB causes cell-specific changes in chemosensory tuning, even among similar projection neurons. NEW & NOTEWORTHY Norepinephrine (NE) is released throughout the brain in many behavioral contexts, but its impacts on information processing are not well understood. We studied the impact of NE on chemosensory tuning in the mouse accessory olfactory bulb (AOB). Electrophysiological recordings from AOB neurons in ex vivo preparations revealed that NE, on balance, inhibited mitral cell responses to chemosensory cues. However, NE’s effects were heterogeneous, indicating that NE signaling reshapes AOB output in a cell- and stimulus-specific manner.

scholarly journals Neural mechanisms of social learning in the female mouse

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Yuan Gao ◽  
Carl Budlong ◽  
Emily Durlacher ◽  
Ian G Davison
Keyword(s):  
Olfactory Bulb ◽  
Social Interactions ◽  
Ex Vivo ◽  
Neural Mechanisms ◽  
Projection Neurons ◽  
Accessory Olfactory Bulb ◽  
Membrane Excitability ◽  
Fluorescent Reporter ◽  
Neuroendocrine Responses ◽  
Activity Dependence

Social interactions are often powerful drivers of learning. In female mice, mating creates a long-lasting sensory memory for the pheromones of the stud male that alters neuroendocrine responses to his chemosignals for many weeks. The cellular and synaptic correlates of pheromonal learning, however, remain unclear. We examined local circuit changes in the accessory olfactory bulb (AOB) using targeted ex vivo recordings of mating-activated neurons tagged with a fluorescent reporter. Imprinting led to striking plasticity in the intrinsic membrane excitability of projection neurons (mitral cells, MCs) that dramatically curtailed their responsiveness, suggesting a novel cellular substrate for pheromonal learning. Plasticity was selectively expressed in the MC ensembles activated by the stud male, consistent with formation of memories for specific individuals. Finally, MC excitability gained atypical activity-dependence whose slow dynamics strongly attenuated firing on timescales of several minutes. This unusual form of AOB plasticity may act to filter sustained or repetitive sensory signals.

scholarly journals Gut-Ex-Vivo system as a model to study gluten response in celiac disease

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Mara Gagliardi ◽  
Nausicaa Clemente ◽  
Romina Monzani ◽  
Luca Fusaro ◽  
Eleonora Ferrari ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Intestinal Epithelium ◽  
Complex Disease ◽  
Ex Vivo ◽  
Dynamic Condition ◽  
Model Systems ◽  
In Vivo Models ◽  
Effective Manner ◽  
Junction Protein ◽  
The Impact

AbstractCeliac disease (CD) is a complex immune-mediated chronic disease characterized by a consistent inflammation of the gastrointestinal tract induced by gluten intake in genetically predisposed individuals. Although initiated by the interaction between digestion-derived gliadin, a gluten component, peptides, and the intestinal epithelium, the disorder is highly complex and involving other components of the intestine, such as the immune system. Therefore, conventional model systems, mainly based on two- or three-dimension cell cultures and co-cultures, cannot fully recapitulate such a complex disease. The development of mouse models has facilitated the study of different interacting cell types involved in the disorder, together with the impact of environmental factors. However, such in vivo models are often expensive and time consuming. Here we propose an organ ex vivo culture (gut-ex-vivo system) based on small intestines from gluten-sensitive mice cultivated in a dynamic condition, able to fully recapitulate the biochemical and morphological features of the mouse model exposed to gliadin (4 weeks), in 16 h. Indeed, upon gliadin exposure, we observed: i) a down-regulation of cystic fibrosis transmembrane regulator (CFTR) and an up-regulation of transglutaminase 2 (TG2) at both mRNA and protein levels; ii) increased intestinal permeability associated with deregulated tight junction protein expression; iii) induction and production of pro-inflammatory cytokines such as interleukin (IL)-15, IL-17 and interferon gamma (IFNγ); and iv) consistent alteration of intestinal epithelium/villi morphology. Altogether, these data indicate that the proposed model can be efficiently used to study the pathogenesis of CD, test new or repurposed molecules to accelerate the search for new treatments, and to study the impact of the microbiome and derived metabolites, in a time- and cost- effective manner.

scholarly journals Experimental Models to Study COVID-19 Effect in Stem Cells

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 91
Author(s):  
Rishi Man Chugh ◽  
Payel Bhanja ◽  
Andrew Norris ◽  
Subhrajit Saha
Keyword(s):  
Stem Cells ◽  
Ex Vivo ◽  
Drug Efficacy ◽  
Cell Loss ◽  
Experimental Models ◽  
Model Systems ◽  
Virus Infectivity ◽  
Ex Vivo Model ◽  
Global Pandemic ◽  
The Impact

The new strain of coronavirus (severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)) emerged in 2019 and hence is often referred to as coronavirus disease 2019 (COVID-19). This disease causes hypoxic respiratory failure and acute respiratory distress syndrome (ARDS), and is considered as the cause of a global pandemic. Very limited reports in addition to ex vivo model systems are available to understand the mechanism of action of this virus, which can be used for testing of any drug efficacy against virus infectivity. COVID-19 induces tissue stem cell loss, resulting inhibition of epithelial repair followed by inflammatory fibrotic consequences. Development of clinically relevant models is important to examine the impact of the COVID-19 virus in tissue stem cells among different organs. In this review, we discuss ex vivo experimental models available to study the effect of COVID-19 on tissue stem cells.

scholarly journals Differential impacts of repeated sampling on odor representations by genetically-defined mitral and tufted cell subpopulations in the mouse olfactory bulb

2020 ◽  
Author(s):  
Thomas P. Eiting ◽  
Matt Wachowiak
Keyword(s):  
Information Processing ◽  
Olfactory Bulb ◽  
High Frequency ◽  
Response Patterns ◽  
Repeated Sampling ◽  
Tufted Cell ◽  
Cell Subpopulations ◽  
Genetic Targeting ◽  
The Impact ◽  
Over Time

AbstractSniffing—the active control of breathing beyond passive respiration—is used by mammals to modulate olfactory sampling. Sniffing allows animals to make odor-guided decisions within ~200 ms, but animals routinely engage in bouts of high-frequency sniffing spanning several seconds; the impact of such repeated odorant sampling on odor representations remains unclear. We investigated this question in the mouse olfactory bulb, where mitral and tufted cells (MTCs) form parallel output streams of odor information processing. To test the impact of repeated odorant sampling on MTC responses, we used two-photon imaging in anesthetized male and female mice to record activation of MTCs while precisely varying inhalation frequency. A combination of genetic targeting and viral expression of GCaMP6 reporters allowed us to access mitral (MC) and superficial tufted cell (sTC) subpopulations separately. We found that repeated odorant sampling differentially affected responses in MCs and sTCs, with MCs showing more diversity than sTCs over the same time period. Impacts of repeated sampling among MCs included both increases and decreases in excitation, as well as changes in response polarity. Response patterns across ensembles of simultaneously-imaged MCs reformatted over time, with representations of different odorants becoming more distinct. MCs also responded differentially to changes in inhalation frequency, whereas sTC responses were more uniform over time and across frequency. Our results support the idea that MCs and TCs comprise functionally distinct pathways for odor information processing, and suggest that the reformatting of MC odor representations by high-frequency sniffing may serve to enhance the discrimination of similar odors.

scholarly journals Paradoxically sparse chemosensory tuning in broadly-integrating external granule cells in the mouse accessory olfactory bulb

2019 ◽  
Author(s):  
Xingjian Zhang ◽  
Julian P. Meeks
Keyword(s):  
Patch Clamp ◽  
Olfactory Bulb ◽  
Olfactory System ◽  
Granule Cells ◽  
Ex Vivo ◽  
Accessory Olfactory Bulb ◽  
Main Olfactory Bulb ◽  
Patch Clamp Electrophysiology ◽  
Accessory Olfactory System ◽  
Critical Circuit

AbstractThe accessory olfactory bulb (AOB) is a critical circuit in the mouse accessory olfactory system (AOS), but AOB processing is poorly understood compared to the main olfactory bulb (MOB). We used 2-photon GCaMP6f Ca2+ imaging in an ex vivo preparation to study the chemosensory tuning of AOB external granule cells (EGCs), an interneuron population hypothesized to broadly integrate from mitral cells (MCs). We measured MC and EGC tuning to natural chemosignal blends and monomolecular ligands, finding that EGC tuning was far sparser than MC tuning. Simultaneous patch-clamp electrophysiology and Ca2+ imaging indicated that this was only partially explained by lower GCaMP6f-to-spiking ratios in EGCs compared to MCs. Ex vivo patch-clamp recordings revealed that EGC subthreshold responsivity was broad, but monomolecular ligand responses were insufficient to elicit spiking. These results indicate that EGC spiking is selectively engaged by chemosensory blends, suggesting different roles for EGCs than analogous interneurons in the MOB.

scholarly journals Synchronous Infra-Slow Oscillations Organize Ensembles of Accessory Olfactory Bulb Projection Neurons into Distinct Microcircuits

2020 ◽  
Vol 40 (21) ◽  
pp. 4203-4218 ◽  
Author(s):  
Chryssanthi Tsitoura ◽  
Sebastian T. Malinowski ◽  
Julia Mohrhardt ◽  
Rudolf Degen ◽  
Brett T. DiBenedictis ◽  
...  
Keyword(s):  
Olfactory Bulb ◽  
Projection Neurons ◽  
Accessory Olfactory Bulb ◽  
Slow Oscillations

scholarly journals Interdependent Conductances Drive Infraslow Intrinsic Rhythmogenesis in a Subset of Accessory Olfactory Bulb Projection Neurons

2016 ◽  
Vol 36 (11) ◽  
pp. 3127-3144 ◽  
Author(s):  
M. Gorin ◽  
C. Tsitoura ◽  
A. Kahan ◽  
K. Watznauer ◽  
D. R. Drose ◽  
...  
Keyword(s):  
Olfactory Bulb ◽  
Projection Neurons ◽  
Accessory Olfactory Bulb
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