Linear correlation between the number of olfactory sensory neurons expressing a given mouse odorant receptor gene and the total volume of the corresponding glomeruli in the olfactory bulb

Bressel, Olaf Christian; Khan, Mona; Mombaerts, Peter

doi:10.1002/cne.23835

Cited by 71 publications

(80 citation statements)

References 35 publications

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“…3B), as previously demonstrated (5). Similarly, Bressel et al recently showed a strong linear correlation between OSN number in the MOE and total glomerular volume in the OB (16). Studies demonstrating strong OSN and glomerular size correlations point toward glomerular measurements as surrogate measurements for estimating OSN number counts in transgenic mouse lines in which OR genes are genetically tagged.…”

Section: Behavioral Responses Following Olfactory Fear Acquisition Ansupporting

confidence: 60%

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

Morrison

Dias

Ressler

2015

Proc. Natl. Acad. Sci. U.S.A.

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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 learninginduced freezing behavior, structural alterations, and enhanced neural sensory representation can be reversed in adult mice following extinction training.fear extinction | olfaction | neural plasticity I ncreasing evidence suggests that the cellular, neuroanatomical, and receptive field organizations of vertebrate sensory systems are continually reshaped throughout adulthood by cues from the external environment. Activity-dependent changes are known to occur both during critical periods of development and also in the adult brain, allowing the animal to optimally perform behaviors based on the demands of the surrounding environment. Postmitotic organizational changes, along with activity-dependent plasticity, have been largely implicated in shaping sensory circuits from development through adulthood (1-4). In particular, the olfactory sensory system of adult mice exhibits functional and neuroanatomical learning-dependent changes following olfactory fear conditioning in adulthood (5-7). The M71-LacZ transgenic mouse line expresses LacZ under the M71 odorant receptor (OR) promoter (encoded by the olfactory receptor 151 gene, Olfr151) (8) in the M71 OR-expressing, acetophenone-responsive population of olfactory sensory neurons (OSNs). Using this line, we previously demonstrated an increased number of M71-expressing OSNs in the main olfactory epithelium (MOE) of adult mice following olfactory fear conditioning to acetophenone (5, 7), an odorant that activates the M71/M72 ORs (9, 10). This increase in receptor-specific OSNs within the MOE was directly correlated with an increase in the area of M71+ axons innervating the M71 glomeruli within the olfactory bulbs (OBs). Behaviorally, these olfactory fear-conditioned mice also exhibited enhanced fear-potentiated startle (FPS) and freezing specific to the conditioned odor stimulus. Notably such changes were never seen with equivalent odorant exposure alone but only when the odorant was paired with an aversive or appetitive cue (5, 7), sugges...

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Section: Behavioral Responses Following Olfactory Fear Acquisition Ansupporting

confidence: 60%

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

Morrison

Dias

Ressler

2015

Proc. Natl. Acad. Sci. U.S.A.

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“…We found that in n5247MCZ mice at PD22, the ectopic anterior glomeruli contribute 20.0% (SD ± 6.5%) to the total glomerular volume per mouse, using methods outlined in Bressel et al (2016). It follows that ∼20% of Nrp1 – M71 + OSNs innervate these ectopic anterior glomeruli.…”

Section: Resultsmentioning

confidence: 84%

“…M71 is expressed in a few thousand OSNs at PD21 (Bressel et al, 2016). In mice that carry the gene-targeted M71-IRES-tauGFP mutation (Potter et al, 2001), M71 + OSNs express tauGFP along with M71 from bicistronic transcripts.…”

Section: Resultsmentioning

confidence: 99%

“…We have described a linear relationship between the number of OSNs that express a given OR gene and the total volume of the corresponding glomeruli in the bulbs (Bressel et al, 2016). We found that in n5247MCZ mice at PD22, the ectopic anterior glomeruli contribute 20.0% (SD ± 6.5%) to the total glomerular volume per mouse, using methods outlined in Bressel et al (2016).…”

Section: Resultsmentioning

confidence: 99%

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Neuropilin-1 and the Positions of Glomeruli in the Mouse Olfactory Bulb

Zapiec

Bressel

Khan

et al. 2016

eNeuro

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It is known since 1996 that mouse odorant receptors (ORs) are involved in determining the positions of the sites of coalescence of axons of olfactory sensory neurons (OSNs)—the thousands of glomeruli in the olfactory bulb. But the molecular and cellular mechanisms of OR-mediated axonal coalescence into glomeruli remain unclear. A model was proposed in 2006–2009 whereby OR-derived cAMP signals, rather than direct action of OR molecules, determine the target destinations (glomeruli) of OSNs in the bulb. This model hypothesizes that OR-derived cAMP signals determine the expression levels of neuropilin 1 (Nrp1) in OSN axon termini; that levels of Nrp1 in glomeruli form a gradient from anterior-low to posterior-high throughout the bulb; and that these Nrp1 levels mechanistically determine anterior-posterior patterning of glomeruli. Here, we describe the first independent evaluation of the Nrp1 model since it was formulated a decade ago. We tested the model for the well-characterized mouse OR M71 using our gene-targeted mouse strains, which are publicly available. In contradiction to the model, we observed a variety of configurations for the M71 glomeruli in the conditional Nrp1 knockout. We then reassessed the model for the original OR transgene with which the model was developed, using the same publicly available mouse strains. We discovered that glomerular positions do not undergo the simple anterior shift that has been reported in the conditional Nrp1 knockout for this OR transgene. Taken together, our findings do not support the Nrp1 model for the anterior-posterior patterning of glomerular positions in the olfactory bulb.

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“…In anesthetized rats, the CV of single OSN firing was found to be on the order of 1 (Duchamp-Viret et al, 2005). Single glomeruli receive a few thousand sensory axons although this number can vary significantly depending on receptor gene (Bressel et al, 2016). If OSNs were statistically independent of each other, the glomerular CV is expected to be on the order of 1–2%.…”

Section: Discussionmentioning

confidence: 99%

Reading Out Olfactory Receptors: Feedforward Circuits Detect Odors in Mixtures without Demixing

Mathis

Rokni

Kapoor

et al. 2016

Neuron

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The olfactory system, like other sensory systems, can detect specific stimuli of interest amidst complex, varying backgrounds. To gain insight into the neural mechanisms underlying this ability, we imaged responses of mouse olfactory bulb glomeruli to mixtures. We used this data to build a model of mixture responses that incorporated nonlinear interactions and trial-to-trial variability and explored potential decoding mechanisms that can mimic mouse performance when given glomerular responses as input. We find that a linear decoder with sparse weights could match mouse performance using just a small subset of the glomeruli (~15). However, when such a decoder is trained only with single odors, it generalizes poorly to mixture stimuli due to nonlinear mixture responses. We show that mice similarly fail to generalize, suggesting that they learn this segregation task discriminatively by adjusting task-specific decision boundaries without taking advantage of a demixed representation of odors.

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Linear correlation between the number of olfactory sensory neurons expressing a given mouse odorant receptor gene and the total volume of the corresponding glomeruli in the olfactory bulb

Cited by 71 publications

References 35 publications

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

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

Neuropilin-1 and the Positions of Glomeruli in the Mouse Olfactory Bulb

Reading Out Olfactory Receptors: Feedforward Circuits Detect Odors in Mixtures without Demixing

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