scholarly journals Massive normalization of olfactory bulb output in mice with a 'monoclonal nose'

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Benjamin Roland ◽  
Rebecca Jordan ◽  
Dara L Sosulski ◽  
Assunta Diodato ◽  
Izumi Fukunaga ◽  
...  
Keyword(s):  
Olfactory Bulb ◽  
Transgenic Mice ◽  
Neural Correlates ◽  
Mitral Cell ◽  
Inhibitory Circuits ◽  
Cell Responses ◽  
Mechanistic Basis ◽  
Signal Normalization ◽  
Whole Cell Recordings

Perturbations in neural circuits can provide mechanistic understanding of the neural correlates of behavior. In M71 transgenic mice with a “monoclonal nose”, glomerular input patterns in the olfactory bulb are massively perturbed and olfactory behaviors are altered. To gain insights into how olfactory circuits can process such degraded inputs we characterized odor-evoked responses of olfactory bulb mitral cells and interneurons. Surprisingly, calcium imaging experiments reveal that mitral cell responses in M71 transgenic mice are largely normal, highlighting a remarkable capacity of olfactory circuits to normalize sensory input. In vivo whole cell recordings suggest that feedforward inhibition from olfactory bulb periglomerular cells can mediate this signal normalization. Together, our results identify inhibitory circuits in the olfactory bulb as a mechanistic basis for many of the behavioral phenotypes of mice with a “monoclonal nose” and highlight how substantially degraded odor input can be transformed to yield meaningful olfactory bulb output.

Olfactory deficit is associated with mitral cell dysfunction in the olfactory bulb of P301S tau transgenic mice

2019 ◽  
Vol 148 ◽  
pp. 34-45 ◽  
Author(s):  
Shanshan Li ◽  
Weiyun Li ◽  
Xuewei Wu ◽  
Jing Li ◽  
Jing Yang ◽  
...  
Keyword(s):  
Olfactory Bulb ◽  
Transgenic Mice ◽  
Mitral Cell ◽  
Cell Dysfunction ◽  
Olfactory Deficit

scholarly journals Differences in olfactory bulb mitral cell spiking with ortho- and retronasal stimulation revealed by data-driven models

2021 ◽  
Vol 17 (9) ◽  
pp. e1009169
Author(s):  
Michelle F. Craft ◽  
Andrea K. Barreiro ◽  
Shree Hari Gautam ◽  
Woodrow L. Shew ◽  
Cheng Ly
Keyword(s):  
Olfactory Bulb ◽  
Nasal Cavity ◽  
Electrode Array ◽  
Cell Types ◽  
Mitral Cell ◽  
Data Driven ◽  
Linear Filters ◽  
Filter Model ◽  
Using Data

The majority of olfaction studies focus on orthonasal stimulation where odors enter via the front nasal cavity, while retronasal olfaction, where odors enter the rear of the nasal cavity during feeding, is understudied. The coding of retronasal odors via coordinated spiking of neurons in the olfactory bulb (OB) is largely unknown despite evidence that higher level processing is different than orthonasal. To this end, we use multi-electrode array in vivo recordings of rat OB mitral cells (MC) in response to a food odor with both modes of stimulation, and find significant differences in evoked firing rates and spike count covariances (i.e., noise correlations). Differences in spiking activity often have implications for sensory coding, thus we develop a single-compartment biophysical OB model that is able to reproduce key properties of important OB cell types. Prior experiments in olfactory receptor neurons (ORN) showed retro stimulation yields slower and spatially smaller ORN inputs than with ortho, yet whether this is consequential for OB activity remains unknown. Indeed with these specifications for ORN inputs, our OB model captures the salient trends in our OB data. We also analyze how first and second order ORN input statistics dynamically transfer to MC spiking statistics with a phenomenological linear-nonlinear filter model, and find that retro inputs result in larger linear filters than ortho inputs. Finally, our models show that the temporal profile of ORN is crucial for capturing our data and is thus a distinguishing feature between ortho and retro stimulation, even at the OB. Using data-driven modeling, we detail how ORN inputs result in differences in OB dynamics and MC spiking statistics. These differences may ultimately shape how ortho and retro odors are coded.

scholarly journals Spontaneous activity generated within the olfactory bulb establishes the discrete wiring of mitral cell dendrites

2019 ◽  
Author(s):  
Satoshi Fujimoto ◽  
Marcus N. Leiwe ◽  
Richi Sakaguchi ◽  
Yuko Muroyama ◽  
Reiko Kobayakawa ◽  
...  
Keyword(s):  
Olfactory Bulb ◽  
Spontaneous Activity ◽  
Neuronal Activity ◽  
Primary Dendrite ◽  
Sensory Information ◽  
Mitral Cell ◽  
Network Activity ◽  
Mitral Cells ◽  
Tufted Cells

ABSTRACTIn the mouse olfactory bulb, sensory information detected by ∼1,000 types of olfactory sensory neurons (OSNs) is represented by the glomerular map. The second-order neurons, mitral and tufted cells, connect a single primary dendrite to one glomerulus. This forms discrete connectivity between the ∼1,000 types of input and output neurons. It has remained unknown how this discrete dendrite wiring is established during development. We found that genetically silencing neuronal activity in mitral cells, but not from OSNs, perturbs the dendrite pruning of mitral cells. In vivo calcium imaging of awake neonatal animals revealed two types of spontaneous neuronal activity in mitral/tufted cells, but not in OSNs. Pharmacological and knockout experiments revealed a role for glutamate and NMDARs. The genetic blockade of neurotransmission among mitral/tufted cells reduced spontaneous activity and perturbed dendrite wiring. Thus, spontaneous network activity generated within the olfactory bulb self-organizes the parallel discrete connections in the mouse olfactory system.

scholarly journals Multiple signals evoked by unisensory stimulation converge onto cerebellar granule and Purkinje cells in mice

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Misa Shimuta ◽  
Izumi Sugihara ◽  
Taro Ishikawa
Keyword(s):  
Purkinje Cells ◽  
Granule Cells ◽  
Late Phase ◽  
Two Phase ◽  
Cell Responses ◽  
Different Types ◽  
Peripheral Sensory ◽  
Whole Cell Recordings ◽  
Complex Spikes

AbstractThe cerebellum receives signals directly from peripheral sensory systems and indirectly from the neocortex. Even a single tactile stimulus can activate both of these pathways. Here we report how these different types of signals are integrated in the cerebellar cortex. We used in vivo whole-cell recordings from granule cells and unit recordings from Purkinje cells in mice in which primary somatosensory cortex (S1) could be optogenetically inhibited. Tactile stimulation of the upper lip produced two-phase granule cell responses (with latencies of ~8 ms and 29 ms), for which only the late phase was S1 dependent. In Purkinje cells, complex spikes and the late phase of simple spikes were S1 dependent. These results indicate that individual granule cells combine convergent inputs from the periphery and neocortex and send their outputs to Purkinje cells, which then integrate those signals with climbing fiber signals from the neocortex.

Action of some drugs on gecko olfactory bulb mitral cell responses to odor stimulation

1979 ◽  
Vol 167 (1) ◽  
pp. 180-184 ◽  
Author(s):  
Keiichi Tonosaki ◽  
Tatsuaki Shibuya
Keyword(s):  
Olfactory Bulb ◽  
Mitral Cell ◽  
Cell Responses

Modulation by prostaglandin D2 of mitral cell responses to odor stimulation in rabbit olfactory bulb

1986 ◽  
Vol 378 (2) ◽  
pp. 216-222 ◽  
Author(s):  
Yasuyoshi Watanabe ◽  
Kensaku Mori ◽  
Kazuyuki Imamura ◽  
Sadayuki F. Takagi ◽  
Osamu Hayaishi
Keyword(s):  
Olfactory Bulb ◽  
Mitral Cell ◽  
Prostaglandin D2 ◽  
Cell Responses

scholarly journals Mice transgenic for a soluble form of murine CTLA-4 show enhanced expansion of antigen-specific CD4+ T cells and defective antibody production in vivo.

1994 ◽  
Vol 179 (3) ◽  
pp. 809-817 ◽  
Author(s):  
F Ronchese ◽  
B Hausmann ◽  
S Hubele ◽  
P Lane
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Transgenic Mice ◽  
T Cell Activation ◽  
Antibody Production ◽  
T Cell Responses ◽  
Soluble Form ◽  
Cell Responses

CD4+ T cell responses were analyzed in transgenic mice expressing a soluble form of murine CTLA-4, mCTLA4-H gamma 1, which blocks the interaction of the T cell activation molecules CD28 and CTLA-4 with their costimulatory ligands. Consistent with previous reports (Linsley, P. S., P. M. Wallace, J. Johnson, M. G. Gibson, J. L. Greene, J. A. Ledbetter, C. Singh, and M. A. Tepper. 1992. Science (Wash. DC). 257:792), T cell-dependent antibody production was profoundly inhibited in mCTLA4-H gamma 1 transgenic mice immunized with a protein antigen. Surprisingly, however, transgenic mice could generate quantitatively and qualitatively normal primary T cell responses, as measured by limiting dilution assays and lymphokine production. In addition, in vivo expansion of antigen-specific T cells after secondary or tertiary immunization was enhanced in mCTLA4-H gamma 1 transgenics as compared with normal mice. Although unable to deliver cognate help to B cells in vivo, T cells from mCTLA4-H gamma 1 transgenic mice were not anergic as they could help B cells to produce specific antibodies when adoptively transferred into nude hosts. Taken together, these data suggest that the engagement of CD28 and/or CTLA-4 may not be required for the induction of T cell responses, as is currently understood, but rather for the expression of T cell effector function such as the delivery of T cell help to B cells.

scholarly journals Bursting mitral cells time the oscillatory coupling between olfactory bulb and entorhinal networks in neonatal mice

2020 ◽  
Author(s):  
Johanna K. Kostka ◽  
Sabine Gretenkord ◽  
Ileana L. Hanganu-Opatz
Keyword(s):  
Olfactory Bulb ◽  
Entorhinal Cortex ◽  
Mitral Cell ◽  
Network Activity ◽  
List Type ◽  
Mitral Cells ◽  
Early Postnatal Development ◽  
Theta Phase

ABSTRACTShortly after birth, the olfactory system provides to blind, deaf, non-whisking and motorically-limited rodents not only the main source of environmental inputs, but also the drive boosting the functional entrainment of limbic circuits. However, the cellular substrate of this early communication remains largely unknown. Here we combine in vivo and in vitro patch-clamp and extracellular recordings to reveal the contribution of mitral cell (MC) firing to the early patterns of network activity in the neonatal olfactory bulb (OB) and lateral entorhinal cortex (LEC), the gatekeeper of limbic circuits. We show that MCs predominantly fire either in an irregular bursting or non-bursting pattern during discontinuous theta events in OB. However, the temporal spike-theta phase coupling is stronger for bursting MCs when compared to non-bursting cells. In line with the direct OB projections to LEC, both bursting and non-bursting firing augments during coordinated patterns of entorhinal activity, yet to a higher magnitude for bursting MCs. These cells are stronger temporally coupled to the discontinuous theta events in LEC. Thus, bursting MCs might drive the entrainment of OB-LEC network during neonatal development.KEY POINTSDuring early postnatal development mitral cells show either irregular bursting or non-bursting firing patternsBursting mitral cells preferentially fire during theta bursts in the neonatal OB, being locked to the theta phaseBursting mitral cells preferentially fire during theta bursts in the neonatal lateral entorhinal cortex and are temporally related to both respiration rhythm- and theta phaseBursting mitral cells act as cellular substrate of the olfactory drive promoting the oscillatory entrainment of entorhinal networks

scholarly journals Screening HLA-A-restricted T cell epitopes of SARS-CoV-2 and the induction of CD8+ T cell responses in HLA-A transgenic mice

2021 ◽  
Author(s):  
Xiaoxiao Jin ◽  
Yan Ding ◽  
Shihui Sun ◽  
Xinyi Wang ◽  
Zining Zhou ◽  
...  
Keyword(s):  
T Cell ◽  
Transgenic Mice ◽  
T Cell Responses ◽  
Poly I:C ◽  
T Cell Epitopes ◽  
Wild Type ◽  
Cell Responses ◽  
Asian Populations ◽  
Donor Pbmcs

AbstractSince severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-specific T cells have been found to play essential roles in host immune protection and pathology in patients with coronavirus disease 2019 (COVID-19), this study focused on the functional validation of T cell epitopes and the development of vaccines that induce specific T cell responses. A total of 120 CD8+ T cell epitopes from the E, M, N, S, and RdRp proteins were functionally validated. Among these, 110, 15, 6, 14, and 12 epitopes were highly homologous with SARS-CoV, OC43, NL63, HKU1, and 229E, respectively; in addition, four epitopes from the S protein displayed one amino acid that was distinct from the current SARS-CoV-2 variants. Then, 31 epitopes restricted by the HLA-A2 molecule were used to generate peptide cocktail vaccines in combination with Poly(I:C), R848 or poly (lactic-co-glycolic acid) nanoparticles, and these vaccines elicited robust and specific CD8+ T cell responses in HLA-A2/DR1 transgenic mice as well as wild-type mice. In contrast to previous research, this study established a modified DC-peptide-PBL cell coculture system using healthy donor PBMCs to validate the in silico predicted epitopes, provided an epitope library restricted by nine of the most prevalent HLA-A allotypes covering broad Asian populations, and identified the HLA-A restrictions of these validated epitopes using competitive peptide binding experiments with HMy2.CIR cell lines expressing the indicated HLA-A allotype, which initially confirmed the in vivo feasibility of 9- or 10-mer peptide cocktail vaccines against SARS-CoV-2. These data will facilitate the design and development of vaccines that induce antiviral CD8+ T cell responses in COVID-19 patients.

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