Subset Of Mitral Cells Research Articles

Specialized neurons in the right habenula mediate response to aversive olfactory cues.

Hemispheric specializations are well studied at the functional level but less is known about the underlying neural mechanisms. We identified a small cluster of cholinergic neurons in the dorsal habenula (dHb) of zebrafish, defined by their expression of the lecithin retinol acyltransferase domain containing 2 a (lratd2a) gene and their efferent connections with a subregion of the ventral interpeduncular nucleus (vIPN). The lratd2a-expressing neurons in the right dHb are innervated by a subset of mitral cells from both the left and right olfactory bulb and are activated upon exposure to the odorant cadaverine that is repellent to adult zebrafish. Using an intersectional strategy to drive expression of the botulinum neurotoxin specifically in these neurons, we find that adults no longer show aversion to cadaverine. Mutants with left-isomerized dHb that lack these neurons are also less repelled by cadaverine and their behavioral response to alarm substance, a potent aversive cue, is diminished. However, mutants in which both dHb have right identity appear more reactive to alarm substance. The results implicate an asymmetric dHb-vIPN neural circuit in the processing of repulsive olfactory cues and in modulating the resultant behavioral response.

Second‐order input to the medial amygdala from olfactory sensory neurons expressing the transduction channel TRPM5

Recent anatomical tracing experiments in rodents have established that a subset of mitral cells in the main olfactory bulb (MOB) projects directly to the medial amygdala (MeA), traditionally considered a target of the accessory olfactory bulb. Neurons that project from the MOB to the MeA also show activation in response to conspecific (opposite sex) volatile urine exposure, establishing a direct role of the MOB in semiochemical processing. In addition, olfactory sensory neurons (OSNs) that express the transient receptor potential M5 (TRPM5) channel innervate a subset of glomeruli that respond to putative semiochemical stimuli. In this study, we examined whether the subset of glomeruli targeted by TRPM5-expressing OSNs is innervated by the population of mitral cells that projects to the MeA. We injected the retrograde tracer cholera toxin B (CTB) into the MeA of mice in which the TRPM5 promoter drives green fluorescent protein (GFP). We found overlapping clusters of CTB-labeled mitral cell dendritic branches (CTB(+) ) in TRPM5-GFP(+) glomeruli at significantly greater frequency than expected by chance. Despite the significant degree of colocalization, some amygdalopetal mitral cells extended dendrites to non-TRPM5-GFP glomeruli and vice versa, suggesting that, although significant overlapping glomerular innervation is observed between these two features, it is not absolute.

Sparse Incomplete Representations: A Potential Role of Olfactory Granule Cells

Mitral/tufted cells of the olfactory bulb receive odorant information from receptor neurons and transmit this information to the cortex. Studies in awake behaving animals have found that sustained responses of mitral cells to odorants are rare, suggesting sparse combinatorial representation of the odorants. Careful alignment of mitral cell firing with the phase of the respiration cycle revealed brief transient activity in the larger population of mitral cells, which respond to odorants during a small fraction of the respiration cycle. Responses of these cells are therefore temporally sparse. Here, we propose a mathematical model for the olfactory bulb network that can reproduce both combinatorially and temporally sparse mitral cell codes. We argue that sparse codes emerge as a result of the balance between mitral cells' excitatory inputs and inhibition provided by the granule cells. Our model suggests functional significance for the dendrodendritic synapses mediating interactions between mitral and granule cells.

Stabilisation of beta and gamma oscillation frequency in the mammalian olfactory bulb

The dynamics of the mammalian olfactory bulb (OB) is characterized by local field potential (LFP) oscillations either slow, in the theta range (2-10Hz, tightly linked to the respiratory rhythm), or fast, in the beta (15-30Hz) or gamma (40-90Hz) range. These fast oscillations are known to be modulated by odorant features [1] and animal experience or state [2][3], but both their mechanisms and implication in coding are still not well understood. In this study, we used a double canulation protocol to impose artificial breathing rhythms to anesthetized rats while recording the LFP in the OB. We observed that despite the changes in the input air flow parameters (frequency or flow rate), the main characteristics of fast oscillations (duration, frequency or amplitude) were merely constant. We thus made the hypothesis that fast beta and gamma oscillations dynamics are entirely determined by the OB network properties and that external stimulation was only able put the network in a state which permits the generation of one or the other oscillations (they are never present simultaneously). To test this hypothesis, we studied a simplified OB model based on previous modeling studies. In particular it includes resonant mitral cells [4] and graded synaptic inhibition [5]. Detailed analysis and numerical simulations of the model showed that two oscillatory dynamical regime can be sustained. First, a low noise regime where at each cycle, a subset of mitral cells are tightly synchronized and yield a saturation of the graded inhibition, during which mitral cell discharge is prevented. Because of this saturation, the network frequency is governed by the dynamics of the graded inhibition decay. Interestingly, this dynamics is not very sensitive to the number of mitral cells that lead to the saturation. Consequently, there is a wide range of mitral cell firing rate during which the network frequency is stable. Using standard parameters in our model, we found an oscillation frequency stable between 25 and 30Hz while the average mitral cell firing rate increased from 5Hz to 25Hz. Second, a high noise regime can be observed where the mitral cell discharge is much less regular. In this case, the network oscillations are of lower amplitude compared to the low noise regime and thus the graded inhibition is never saturated by fluctuations around its mean. The network can then be well described by a mean field approach (as described in [ 6]) and is close to a previous model of in vitro gamma oscillations [4]. With our model parameters, oscillations in this regime have higher frequency, typically in the gamma range (50Hz-90Hz) but their frequency is highly sensitive to the level of input excitation to the mitral cells. This discrepancy with our experimental result could be relieved by the in vitro experimental observation that mitral cell stimulus excitatory input is all or none [7]. Indeed this could provide a stable external input to the network and thus also stabilize the gamma frequency. Finally, we have shown that our model can account for the two stable oscillatory regimes observed in the OB in vivo. However our model does not take into account the spatial activation of the OB and the study of how spatially segregated oscillatory generators interact and potentially synchronize is an ongoing work.

5-hydroxytryptamine action in the rat olfactory bulb: In vitro electrophysiological patch-clamp recordings of juxtaglomerular and mitral cells

The olfactory bulb, first relay of olfactory pathways, is densely innervated by serotoninergic centrifugal fibers originating from the raphe nuclei. Although serotonin innervation was reported to be involved in olfactory learning in mammals, the action of this neurotransmitter on its putative cellular targets has been never described through unitary recordings. This lack of data initiated the present study where the effects of 5HT on juxtaglomerular and mitral cells are analyzed using whole-cell recordings on olfactory bulb slices. Serotonin depolarizes 34% of 525 JG cells. A multivariate statistical analysis of juxtaglomerular cells characteristics shows that the serotonin responsive cell group can be individualized regarding their tonic discharge-mode in response to a direct current injection, their lower expression of hyperpolarization-activated cation current and their low membrane capacities. The use of ion channel blockers and ramp voltage protocol indicate that serotoninergic depolarization of juxtaglomerular cells may be due to a nonselective cation current with a reversal potential of −44 mV. Pharmacological tests with serotonin receptor antagonists and agonists reveal that 5HT action on juxtaglomerular cells would be mainly mediated by 5HT 2C receptors. In mitral cells, serotonin acts on 49.1% of the 242 tested cells, inducing two types of responses. A first subset of mitral cells (26.8%, n=65) were hyperpolarized by serotonin. This response would be indirect and mediated by action of GABA on GABA A receptors since it was antagonized by bicuculline. The involved GABAergic neurons are hypothesized to be juxtaglomerular and granular cells, on which serotonin would act mainly via 5HT 2C and via 5HT 2A receptors respectively. The second subset of mitral cells (22.3%, n=54) were directly depolarized by serotonin acting through 5HT 2A receptors. Our data on serotonin action on juxtaglomerular cells and mitral cells reveal a part of functional mechanisms whereby serotonin can act on olfactory bulb network. This is expected to enrich the understanding of its determining role in olfactory learning.