Main Olfactory Bulb Glomeruli Research Articles

P/Q Type Calcium Channel Cav2.1 Defines a Unique Subset of Glomeruli in the Mouse Olfactory Bulb.

Voltage-gated calcium (Cav) channels are a prerequisite for signal transmission at the first olfactory sensory neuron (OSN) synapse within the glomeruli of the main olfactory bulb (MOB). We showed previously that the N-type Cav channel subunit Cav2.2 is present in the vast majority of glomeruli and plays a central role in presynaptic transmitter release. Here, we identify a distinct subset of glomeruli in the MOB of adult mice that is characterized by expression of the P/Q-type channel subunit Cav2.1. Immunolocalization shows that Cav2.1+ glomeruli reside predominantly in the medial and dorsal MOB, and in the vicinity of the necklace glomerular region close to the accessory olfactory bulb. Few glomeruli are detected on the ventral and lateral MOB. Cav2.1 labeling in glomeruli colocalizes with the presynaptic marker vGlut2 in the axon terminals of OSNs. Electron microscopy shows that Cav2.1+ presynaptic boutons establish characteristic asymmetrical synapses with the dendrites of second-order neurons in the glomerular neuropil. Cav2.1+ glomeruli receive axonal input from OSNs that express molecules of canonical OSNs: olfactory marker protein, the ion channel Cnga2, and the phosphodiesterase Pde4a. In the main olfactory epithelium, Cav2.1 labels a distinct subpopulation of OSNs whose distribution mirrors the topography of the MOB glomeruli, that shows the same molecular signature, and is already present at birth. Together, these experiments identify a unique Cav2.1+ multiglomerular domain in the MOB that may form a previously unrecognized olfactory subsystem distinct from other groups of necklace glomeruli that rely on cGMP signaling mechanisms.

Activation of β-noradrenergic receptors enhances rhythmic bursting in mouse olfactory bulb external tufted cells.

The main olfactory bulb (MOB) receives a rich noradrenergic innervation from the nucleus locus coeruleus. Despite the well-documented role of norepinephrine and β-adrenergic receptors in neonatal odor preference learning, identified cellular physiological actions of β-receptors in the MOB have remained elusive. β-Receptors are expressed at relatively high levels in the MOB glomeruli, the location of external tufted (ET) cells that exert an excitatory drive on mitral and other cell types. The present study investigated the effects of β-receptor activation on the excitability of ET cells with patch-clamp electrophysiology in mature mouse MOB slices. Isoproterenol and selective β2-, but not β1-, receptor agonists were found to enhance two key intrinsic currents involved in ET burst initiation: persistent sodium (INaP) and hyperpolarization-activated inward (Ih) currents. Together, the positive modulation of these currents increased the frequency and strength of ET cell rhythmic bursting. Rodent sniff frequency and locus coeruleus neuronal firing increase in response to novel stimuli or environments. The increase in ET excitability by β-receptor activation may better enable ET cell rhythmic bursting, and hence glomerular network activity, to pace faster sniff rates during heightened norepinephrine release associated with arousal.

Neural Circuit Mechanisms for Pattern Detection and Feature Combination in Olfactory Cortex

Odors are initially encoded in the brain as a set of distinct physicochemical characteristics but are ultimately perceived as a unified sensory object--a "smell." It remains unclear how chemical features encoded by diverse odorant receptors and segregated glomeruli in the main olfactory bulb (MOB) are assembled into integrated cortical representations. Combining patterned optical microstimulation of MOB with in vivo electrophysiological recordings in anterior piriform cortex (PCx), we assessed how cortical neurons decode complex activity patterns distributed across MOB glomeruli. PCx firing was insensitive to single-glomerulus photostimulation. Instead, individual cells reported higher-order combinations of coactive glomeruli resembling odor-evoked sensory maps. Intracellular recordings revealed a corresponding circuit architecture providing each cortical neuron with weak synaptic input from a distinct subpopulation of MOB glomeruli. PCx neurons thus detect specific glomerular ensembles, providing an explicit neural representation of chemical feature combinations that are the hallmark of complex odor stimuli.

Heterogeneous Sensory Innervation and Extensive Intrabulbar Connections of Olfactory Necklace Glomeruli

The mammalian nose employs several olfactory subsystems to recognize and transduce diverse chemosensory stimuli. These subsystems differ in their anatomical position within the nasal cavity, their targets in the olfactory forebrain, and the transduction mechanisms they employ. Here we report that they can also differ in the strategies they use for stimulus coding. Necklace glomeruli are the sole main olfactory bulb (MOB) targets of an olfactory sensory neuron (OSN) subpopulation distinguished by its expression of the receptor guanylyl cyclase GC-D and the phosphodiesterase PDE2, and by its chemosensitivity to the natriuretic peptides uroguanylin and guanylin and the gas CO2. In stark contrast to the homogeneous sensory innervation of canonical MOB glomeruli from OSNs expressing the same odorant receptor (OR), we find that each necklace glomerulus of the mouse receives heterogeneous innervation from at least two distinct sensory neuron populations: one expressing GC-D and PDE2, the other expressing olfactory marker protein. In the main olfactory system it is thought that odor identity is encoded by a combinatorial strategy and represented in the MOB by a pattern of glomerular activation. This combinatorial coding scheme requires functionally homogeneous sensory inputs to individual glomeruli by OSNs expressing the same OR and displaying uniform stimulus selectivity; thus, activity in each glomerulus reflects the stimulation of a single OSN type. The heterogeneous sensory innervation of individual necklace glomeruli by multiple, functionally distinct, OSN subtypes precludes a similar combinatorial coding strategy in this olfactory subsystem.

Afferent activity to necklace glomeruli is dependent on external stimuli

BackgroundThe main olfactory epithelium (MOE) is a complex organ containing several functionally distinct subpopulations of sensory neurons. One such subpopulation is distinguished by its expression of the guanylyl cyclase GC-D. The axons of GC-D-expressing (GC-D+) neurons innervate 9–15 "necklace" glomeruli encircling the caudal main olfactory bulb (MOB). Chemosensory stimuli for GC-D+ neurons include two natriuretic peptides, uroguanylin and guanylin, and CO2. However, the biologically-relevant source of these chemostimuli is unclear: uroguanylin is both excreted in urine, a rich source of olfactory stimuli for rodents, and expressed in human nasal epithelium; CO2 is present in both inspired and expired air.FindingsTo determine whether the principal source of chemostimuli for GC-D+ neurons is external or internal to the nose, we assessed the consequences of removing external chemostimuli for afferent activity to the necklace glomeruli. To do so, we performed unilateral naris occlusions in Gucy2d-Mapt-lacZ +/- mice [which express a β-galactosidase (β-gal) reporter specifically in GC-D+ neurons] followed by immunohistochemistry for β-gal and a glomerular marker of afferent activity, tyrosine hydroxylase (TH). We observed a dramatic decrease in TH immunostaining, consistent with reduced or absent afferent activity, in both necklace and non-necklace glomeruli ipsilateral to the occluded naris.ConclusionLike other MOB glomeruli, necklace glomeruli exhibit a large decrease in afferent activity upon removal of external stimuli. Thus, we conclude that activity in GC-D+ neurons, which specifically innervate necklace glomeruli, is not dependent on internal stimuli. Instead, GC-D+ neurons, like other OSNs in the MOE, primarily sense the external world.

Sexually dimorphic activation of the accessory, but not the main, olfactory bulb in mice by urinary volatiles

Previous research suggests that volatile body odourants detected by the main olfactory epithelium (MOE) are processed mainly by the main olfactory bulb (MOB) whereas nonvolatile body odourants detected by the vomeronasal organ (VNO) are processed via the accessory olfactory bulb (AOB). We asked whether urinary volatiles from males and females differentially activate the AOB in addition to the MOB in gonadectomized mice of either sex. Exposure to urinary volatiles from opposite-sex but not same-sex conspecifics augmented the number of Fos-immunoreactive mitral and granule cells in the AOB. Volatile urinary odours from male as well as female mice also stimulated Fos expression in distinct clusters of MOB glomeruli in both sexes. Intranasal administration of ZnSO(4), intended to disrupt MOE function, eliminated the ability of volatile urinary odours to stimulate Fos in both the MOB and AOB. In ovariectomized, ZnSO(4)-treated females a significant, though attenuated, AOB Fos response occurred after direct nasal exposure to male urine plus soiled bedding, suggesting that VNO signaling remained partially functional in these mice. Future studies will determine whether MOE or VNO signaling, or both types of input, drive the sexually dimorphic response of the AOB to volatile opposite-sex odours and whether this AOB response contributes to reproductive success.

Subdivision of the accessory olfactory bulb in the Japanese common toad, Bufo japonicus, revealed by lectin histochemical analysis

Lectin binding patterns in the olfactory bulb of the Japanese common toad, Bufo japonicus, were examined using 21 types of lectin. Ten out of 21 lectins, WGA, s-WGA, LEL, STL, DBA, VVA, SJA, RCA-I, PNA, and PHA-L, stained the olfactory nerve, the glomeruli in the main olfactory bulb (MOB), the vomeronasal nerve, and the glomeruli in the accessory olfactory bulb (AOB). The binding patterns of LEL, STL, DBA, and PHA-L subdivided AOB glomeruli into rostral and caudal regions, where LEL, STL, and DBA stained the rostral region more intensely than the caudal region, and PHA-L had the opposite effect. Another lectin, BSL-I, stained both AOB glomeruli and the vomeronasal nerve, but not MOB glomeruli or the olfactory nerve. This is the first report of histological subdivision in the AOB of an amphibian, which suggests that the AOB development in Bufo may be unique.

Comparison of odor and mating-induced glomerular activation in the main olfactory bulb of estrous female ferrets

Previously [S.K. Woodley, M.J. Baum, Differential activation of glomeruli in the ferret's main olfactory bulb by anal scent gland odors from males and females: an early step in mate identification, Eur. J. Neurosci. 20 (2004) 1025–1032], the receipt of intromission from a male activated glomeruli (indexed by Fos immunoreactivity in juxtaglomerular cells) in the main olfactory bulb (MOB) of estrous female ferrets which exceeded the activation seen after exposure to male anal scent gland odorants alone. We asked whether centrifugal inputs (e.g., from the locus coeruleus to the MOB) generated by the receipt of vaginal-cervical stimulation influence odor-induced MOB glomerular activation. We compared the activation of MOB glomeruli in estrous female ferrets which received a unilateral naris occlusion prior to exposure to: unscented air, volatile odorants from an anesthetized male, volatile + non-volatile odorants from direct physical contact with an anesthetized male, or mating stimulation. Little glomerular activation was observed in the MOB ipsilateral to an occluded naris, including females which received intromission. An equivalent distribution of activated glomeruli was observed in the ventral MOB of estrous females which either received mating stimulation or had direct physical contact with an anesthetized male. Considerably less glomerular activation occurred in females exposed only to volatile male odors. The MOB of female ferrets responded to body odorants from the opposite sex; however, there was no evidence that mating-induced centrifugal inputs directly activated MOB glomeruli or modified odor-induced glomerular activation.

Novel Microglomerular Structures in the Olfactory Bulb of Mice

The murine olfactory system consists of two primary divisions: (1) a main olfactory system, in which olfactory sensory neurons (OSNs) located in the main olfactory epithelium (MOE) send their axons to glomeruli in the main olfactory bulb (MOB); and (2) an accessory olfactory system, in which OSNs located in the vomeronasal organ send their axons to glomeruli in the accessory olfactory bulb (AOB). In labeling studies using the lectin Ulex europaeus agglutinin (UEA), we discovered a novel subset of small neuropilar structures in the MOB that are distinct from other glomeruli both in the MOB and AOB. These "microglomeruli" are morphologically similar to MOB glomeruli in many respects: they receive innervation from processes present in the olfactory nerve layer and are isolated from other glomeruli by juxtaglomerular cells; in addition, the compartmental pattern of UEA labeling suggests the presence of UEA (-) processes within their neuropil. Microglomeruli contained processes that express the olfactory marker protein, a marker common to mature OSN axons. However, unlike other glomerular structures, the microglomeruli did not contain neural cell adhesion molecule-labeled processes. Within microglomeruli, UEA(+) processes interdigitated with MAP2(+) dendrites, some of which likely originate from interneurons, as indicated by glutamic acid decarboxylase labeling. Synaptophysin labeling in microglomeruli strongly suggested that synapses occur between UEA(+) processes and dendrites. Anterograde labeling of OSNs, by injection of rhodamine-dextran into one naris, demonstrated that UEA(+) processes in microglomeruli originated in the MOE. The unique morphology, protein expression, and location of microglomeruli have led us to hypothesize that they represent a novel class of glomerular structures in the murine olfactory system.