Perception of odors by a nonlinear model of the olfactory bulb

The behavior of the olfactory bulb is modeled as a network of interconnected cells with nonlinear dynamics. External inputs from sensory neurons are introduced as perturbations to subsets of cells within the network. We describe the attractors of the system and show how they can be classified and ordered according to their varying degrees of symmetry. By studying networks of attractors in the system's phase space, it is shown how different perturbations may evoke specific switches between various patterns of behavior. This ensures that different odors, even if present at extremely low concentrations, are able to evoke a specific spatio-temporal behavior in the olfactory bulb, permitting their unique perception. The model incorporates many of the processes proposed to mediate perception, such as the topographic organisation of sensory systems, destabilization of cortex by sensory input and synchronisation between neurons. It is also consistent with the character of the olfactory electroencephalogram.     

An olfactory recognition model based on spatio-temporal encoding of odor quality in the olfactory bulb

In order to study the problem how the olfactory neural system processes the odorant molecular information for constructing the olfactory image of each object, we present a dynamic model of the olfactory bulb constructed on the basis of well-established experimental and theoretical results. The information relevant to a single odor, i.e. its constituent odorant molecules and their mixing ratios, are encoded into a spatio-temporal pattern of neural activity in the olfactory bulb, where the activity pattern corresponds to a limit cycle attractor in the mitral cell network. The spatio-temporal pattern consists of a temporal sequence of spatial firing patterns: each constituent molecule is encoded into a single spatial pattern, and the order of magnitude of the mixing ratio is encoded into the temporal sequence. The formation of a limit cycle attractor under the application of a novel odor is carried out based on the intensity-to-time-delay encoding scheme. The dynamic state of the olfactory bulb, which has learned many odors, becomes a randomly itinerant state in which the current firing state of the bulb itinerates randomly among limit cycle attractors corresponding to the learned odors. The recognition of an odor is generated by the dynamic transition in the network from the randomly itinerant state to a limit cycle attractor state relevant to the odor, where the transition is induced by the short-term synaptic changes made according to the Hebbian rule under the application of the odor stimulus. Received: 28 July 1997 / Accepted in revised form: 6 May 1998     

Generation of spike activity by dendrites of secondary neurons of the rat olfactory bulb

Experiments on secondary neurons of the rat olfactory bulb showed the existence of a third region of action potential generation. It evidently consists of dendrites. This is shown by the distance from the soma of the point where action potentials arise initially and by the recording of spontaneous action potentials of comparatively low amplitude, not spreading into the axon. Action potentials are generated by apical dendrites and also, perhaps, by basal dendrites. Besides partial action potentials with stable amplitude, partial action potentials with, for practical purposes, a stepwise changing amplitude also were recorded. It is suggested that the amplitude of the partial action potentials is modified by IPSPs in the spike-generating zones.M. V. Lomonosov Moscow State University. Translated from Neirofiziologiya, Vol. 8, No. 3, pp. 282–290, May–June, 1976.     

The source of spontaneous activity in the main olfactory bulb of the rat

Introduction

In vivo, most neurons in the main olfactory bulb exhibit robust spontaneous activity. This paper tests the hypothesis that spontaneous activity in olfactory receptor neurons drives much of the spontaneous activity in mitral and tufted cells via excitatory synapses.

Methods

Single units were recorded in vivo from the main olfactory bulb of a rat before, during, and after application of lidocaine to the olfactory nerve. The effect of lidocaine on the conduction of action potentials from the olfactory epithelium to the olfactory bulb was assessed by electrically stimulating the olfactory nerve rostral to the application site and monitoring the field potential evoked in the bulb.

Results

Lidocaine caused a significant decrease in the amplitude of the olfactory nerve evoked field potential that was recorded in the olfactory bulb. By contrast, the lidocaine block did not significantly alter the spontaneous activity of single units in the bulb, nor did it alter the field potential evoked by electrical stimulation of the lateral olfactory tract. Lidocaine block also did not change the temporal patters of action potential or their synchronization with respiration.

Conclusions

Spontaneous activity in neurons of the main olfactory bulb is not driven mainly by activity in olfactory receptor neurons despite the extensive convergence onto mitral and tufted cells. These results suggest that spontaneous activity of mitral and tufted is either an inherent property of these cells or is driven by centrifugal inputs to the bulb.     

Response patterns of single neurons in the tortoise olfactory epithelium and olfactory bulb

The responses to odor stimulation of 40 single units in the olfactory mucosa and of 18 units in the olfactory bulb of the tortoise (Gopherus polyphemus) were recorded with indium-filled, Pt-black-tipped microelectrodes. The test battery consisted of 27 odorants which were proved effective by recording from small bundles of olfactory nerve. Two concentrations of each odorant were employed. These values were adjusted for response magnitudes equal to those for amyl acetate at –2.5 and –3.5 log concentration in olfactory twig recording. Varying concentrations were generated by an injection-type olfactometer. The mucosal responses were exclusively facilitory with a peak frequency of 16 impulses/sec. 19 mucosal units responded to at least one odorant and each unit was sensitive to a limited number of odorants (1–15). The sensitivity pattern of each unit was highly individual, with no clear-cut types, either chemical or qualitative, emerging. Of the 18 olfactory bulb units sampled, all responded to at least one odorant. The maximum frequency observed during a response was 39 impulses/sec. The bulbar neurons can be classified into two types. There are neurons that respond exclusively with facilitation and others that respond with facilitation to some odorants and with inhibition to others. Qualitatively or chemically similar odorants did not generate similar patterns across bulbar units.     

Mitral cell differentiation and synaptogenesis of rat presumptive olfactory bulb in organ culture

Summary The ultrastructure of differentiating rat presumptive olfactory bulb in organ culture was investigated with particular reference to mitral cell differentiation and formation of synapses. The presumptive olfactory bulb and olfactory mucosa were dissected en bloc from rat embryos on the fifteenth day of gestation and cultured for 7 days, after which the expiants were examined by electron microscopy. The presumptive olfactory bulb had differentiated into a laminated structure with layers corresponding to the glomerular, external plexiform and mitral cell layers. Mitral-like cells were identified by their location and large cell size. Ultrastructural observations indicated that they were relatively well-differentiated. Their dendrites extended into the glomerular layer in which they were postsynaptic to incoming olfactory axons. The distal part of these dendrites frequently contained coated vesicles. Both asymmetrical and symmetrical synapses were found. The symmetrical synapses involved dendrodendritic contacts between periglomerular cells. Synapses in reciprocal arrangements were not observed in the organ cultures.     

gamma-Aminobutyric acid activity in the olfactory bulb of the rat during the sexual cycle and response to olfactory stimuli.

Glutamic acid decarboxylase activity in the main and accessory olfactory bulbs throughout the sexual cycle of the rat was studied. The effect of male pheromonal secretion on enzyme activity during proestrus and estrus day was also tested. The enzyme activity showed circadian rhythm during the estrous cycle. This rhythm was disrupted during diestrus-2 afternoon in the main bulb and came back during proestrus afternoon. A different pattern of enzyme activity was present in the accessory bulb, since the circadian rhythm was altered during proestrus morning, returning during estrus afternoon. Male odor exposition did not change enzyme profile activity during proestrus day and during estrus morning in the main bulb. In contrast, in the accessory bulb the olfactory stimuli induced opposite changes to that found in rats from the vivarium during proestrus. Comparison of enzyme activity in olfactory stimuli-deprived rats with that of pheromone-stimulated rats during proestrus showed that male odor exposure specifically affects accessory bulb enzyme activity. It is concluded that the changes of the olfactory bulb GABAergic system during proestrus and estrus day, or that evoked by odor stimuli, demonstrate the discriminative response of this system between the accessory olfactory bulb and the main olfactory bulb.     

Histochemical localization of NADPH-diaphorase in the rat accessory olfactory bulb

The distribution of NADPH-diaphorase activity was examined inthe accessory olfactory bulb of the rat using a direct histochemicaltechnique. Labeled fibers and somata were found in all layersof the accessory olfactory bulb. The entire vomeronasal nerveand all vomeronasal glomeruli were strongly labeled, contraryto the main olfactory bulb, where only dorsomedial olfactoryglomeruli displayed NADPH-diaphorase activity. NADPH-diapborasepositive neurons were identified as periglomerular cells inthe glomerular layer and external plexiform layer, horizontalcells in the internal plexiform layer, and granule cells anddeep short-axon cells in the granule cell layer. The labeleddendrites of the granule cells formed a dense neuropile in thegranule cell layer, internal plexiform layer and external plexiformlayer. The staining pattern in the accessory olfactory bulbwas more complex than what has been previously reported, anddemonstrated both similarities and differences with the distributionof NADPH-diaphorase in the main olfactory bulb.     

Local neurons play key roles in the mammalian olfactory bulb

Over the past few decades, research exploring how the brain perceives, discriminates, and recognizes odorant molecules has received a growing interest. Today, olfaction is no longer considered a matter of poetry. Chemical senses entered the biological era when an increasing number of scientists started to elucidate the early stages of the olfactory pathway. A combination of genetic, biochemical, cellular, electrophysiological and behavioral methods has provided a picture of how odor information is processed in the olfactory system as it moves from the periphery to higher areas of the brain. Our group is exploring the physiology of the main olfactory bulb, the first processing relay in the mammalian brain. From different electrophysiological approaches, we are attempting to understand the cellular rules that contribute to the synaptic transmission and plasticity at this central relay. How olfactory sensory inputs, originating from the olfactory epithelium located in the nasal cavity, are encoded in the main olfactory bulb remains a crucial question for understanding odor processing. More importantly, the persistence of a high level of neurogenesis continuously supplying the adult olfactory bulb with newborn local neurons provides an attractive model to investigate how basic olfactory functions are maintained when a large proportion of local neurons are continuously renewed. For this purpose, we summarize the current ideas concerning the molecular mechanisms and organizational strategies used by the olfactory system to encode and process information in the main olfactory bulb. We discuss the degree of sensitivity of the bulbar neuronal network activity to the persistence of this high level of neurogenesis that is modulated by sensory experience. Finally, it is worth mentioning that analyzing the molecular mechanisms and organizational strategies used by the olfactory system to transduce, encode, and process odorant information in the olfactory bulb should aid in understanding the general neural mechanisms involved in both sensory perception and memory. Due to space constraints, this review focuses exclusively on the olfactory systems of vertebrates and primarily those of mammals.     

Histochemical differentiation between nitric oxide synthase-related and -unrelated diaphorase activity in the rat olfactory bulb

The widely used NADPH-diaphorase reaction for demonstrating neuronal nitric oxide synthase is not as specific as previously thought, as it visualizes both a nitric oxide synthase-related activity and a nitric oxide synthase-unrelated diaphorase. In the present study, we used the rat olfactory bulb as a model to characterize the NADPH-diaphorase activity of neuronal nitric oxide synthase histochemically in comparison with neuronal nitric oxide-unrelated diaphorase activity. The NADPH-diaphorase activity of nitric oxide synthase peaked at pH 8 and at Triton X-100 concentrations of 1--2.5%. It was stable in an acidic environment but was reduced in the presence of Triton X-100 and was inactivated by the flavoprotein inhibitor, diphenyleneiodonium. It preferred beta-NADPH as the co-substrate to alpha-NADPH and alpha-NADH. In contrast, nitric oxide synthase-unrelated diaphorase peaked at pH 10, displayed a Triton X-100 optimum at a concentration of 1%, was unstable in an acidic environment and used beta-NADPH, alpha-NADPH and alpha-NADH to similar extents. Differences in the characteristics between neuronal nitric oxide synthase-related and nitric oxide synthase-unrelated NADPH-diaphorase can be used to increase the specificity of the histochemical nitric oxide synthase marker reaction. © Chapman & Hall     

Calbindin D-28k-positive neurons in the rat olfactory bulb

Summary We have studied the distribution of calbindin D-28k immunoreactivity in the rat olfactory bulb using specific monoclonal antibodies and the avidin-biotin-immunoperoxidase method. The largest number of positive neurons was located in the periglomerular layer. These neurons were identified as periglomerular cells; they have been described also by other authors as calbindin-positive elements. Close to these neurons, a second population of nerve cells was identified as superficial shortaxon neurons. The remaining layers showed a smaller number of stained elements. Other labeled neurons were located along the external border of the external plexiform layer; the scarce neurons marking its internal border were identified as van Gehuchten cells. No immunoreactive structures were found in the mitral cell layer, although we observed another population of immunostained short-axon cells at its internal border. Some reactive structures, identified by us as horizontal and vertical cells of Cajal, were located in the boundary zone between the internal plexiform layer and the granule layer. In the white matter, we found a neuronal type characterized by its large size and oriented arborization of varicose dendrites.     

NMDA receptor regulation of cell death in the rat olfactory bulb

Cell death is widespread in the developing nervous system and is under complex regulation by numerous intra- and intercellular mechanisms. Blockade of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor has been shown to promote cell death in the developing brain (Ikonomidou et al., 1999), suggesting that afferent functional activation is an important regulator of cell survival. The olfactory bulb, the first central relay for olfactory information from the nose, is well suited for examining the role of afferent activity in neuronal development. Functional deprivation is easily performed by surgical blockade of airflow to one side of the nasal passage, which results in dramatic alterations in postnatal development of the bulb (Brunjes, 1994), including enhanced neuronal loss (Frazier and Brunjes, 1988; Najbauer and Leon, 1995). The present report examined the specific role of NMDA receptor activation in regulating cell survival within the rat bulb. Pharmacological blockade of receptors with the noncompetitive channel blocker MK-801 (3 x 0.5 mg/kg i.p.) resulted in profound increases in cell death within 24 h. Furthermore, in contrast to other regions, where the effects of receptor blockade were confined to the first 2 postnatal weeks (Ikonomidou et al., 1999), enhancement of cell death was seen in the deeper granule cell-containing regions of the bulb with injections as late as postnatal day 28. In addition, the effects of MK-801 were much more dramatic than those seen after unilateral naris closure, suggesting that NMDA receptor activation may mediate additional survival pathways in the bulb beyond that provided by first nerve input.     

Regulation of spike timing-dependent plasticity of olfactory inputs in mitral cells in the rat olfactory bulb

The recent history of activity input onto granule cells (GCs) in the main olfactory bulb can affect the strength of lateral inhibition, which functions to generate contrast enhancement. However, at the plasticity level, it is unknown whether and how the prior modification of lateral inhibition modulates the subsequent induction of long-lasting changes of the excitatory olfactory nerve (ON) inputs to mitral cells (MCs). Here we found that the repetitive stimulation of two distinct excitatory inputs to the GCs induced a persistent modification of lateral inhibition in MCs in opposing directions. This bidirectional modification of inhibitory inputs differentially regulated the subsequent synaptic plasticity of the excitatory ON inputs to the MCs, which was induced by the repetitive pairing of excitatory postsynaptic potentials (EPSPs) with postsynaptic bursts. The regulation of spike timing-dependent plasticity (STDP) was achieved by the regulation of the inter-spike-interval (ISI) of the postsynaptic bursts. This novel form of inhibition-dependent regulation of plasticity may contribute to the encoding or processing of olfactory information in the olfactory bulb.     

Age-related changes of parvalbumin immunoreactive neurons in the rat main olfactory bulb

Parvalbumin (PV) is found in the olfactory system, including the main olfactory bulb, and is thought to be one of the neuroactive substances in olfaction. Changes in PV immunoreactivity in the olfactory system during aging have not been examined. We investigated such changes in the main olfactory bulb (MOB) of the rat at postnatal month 1 (PM 1), PM 3, PM 6, PM 12 and PM 24. PV-IR neurons were almost completely restricted to the external plexiform layer. At PM 1 there were only a few PV-IR neurons; at PM 3, the number of PV-IR neurons was at its greatest but they were not well developed morphologically. At PM 6, the number of PV-IR neurons was similar to that at PM 3 and they had satellite somata with well-developed processes with many varicosities. By PM 12 the number of neurons and processes had declined, and by PM 24, they had fallen even further and the remaining processes had lost most of their varicosities. We conclude that age-related degeneration of PV-IR neurons in the MOB may reduce calcium buffering and affect olfactory function in senile species.     

Localization and developmental expression of GABAB receptors in the rat olfactory bulb

In this study, we investigated the distribution and developmental expression of the GABA_B receptor subunits, GABA_B1 and GABA_B2, in the main and accessory olfactory bulbs of the rat. Antibodies raised against these subunits strongly labelled the glomerular layer, suggesting that olfactory and vomeronasal nerve fibers express functional GABA_B receptors. Using postembedding immunogold cytochemistry, we found that GABA_B receptors can be present at both extrasynaptic and presynaptic sites of olfactory nerve terminals, and in the latter case they are preferentially associated with the peripheral part of the synaptic specialization. Olfactory nerve fibers expressed GABA_B1 and GABA_B2 at early developmental stages, suggesting that GABA_B receptors may play a role in olfactory development. Output and local neurons of the main and accessory olfactory bulbs were also labelled for GABA_B1 and GABA_B2, although the subcellular distribution patterns of the two subunits were not completely overlapping. These results indicate that presynaptically located GABA_B receptors modulate neurotransmitter release from olfactory and vomeronasal nerve fibers and that, in addition to this presynaptic role, GABA_B receptors may regulate neuronal excitability in infraglomerular circuits.