Modeling the olfactory bulb and its neural oscillatory processings

The olfactory bulb of mammals aids in the discrimination of odors. A mathematical model based on the bulbar anatomy and electrophysiology is described. Simulations of the highly non-linear model produce a 35–60 Hz modulated activity which is coherent across the bulb. The decision states (for the odor information) in this system can be thought of as stable cycles, rather than point stable states typical of simpler neuro-computing models. Analysis shows that a group of coupled non-linear oscillators are responsible for the oscillatory activities. The output oscillation pattern of the bulb is determined by the odor input. The model provides a framework in which to understand the transform between odor input and the bulbar output to olfactory cortex. There is significant correspondence between the model behavior and observed electrophysiology.     

在体神经元胞外记录用于大脑皮层可塑性研究

神经元网络可塑性是大脑学习和记忆功能的基础,可塑性的变化也是某些脑功能疾病的成因。研究大脑皮层可塑性不仅可以为认识可塑性机制提供基本方法,也可对自然衰老过程和神经退行性疾病的病理过程进行观测,进而可以为评价抗衰老药物和治疗神经退行性疾病提供新方法。本文基于经典的大鼠胡须配对模型建立了一套实验方案,通过在体细胞外记录实验的数据分析,比较修剪胡须后相同时间内神经元感受野不对称变化程度的差异,衡量不同生理条件下大鼠体感皮层神经元网络可塑性。本文以中年和青年大鼠体感皮层神经元网络可塑性比较为例,详细介绍了实验方法中的关键技术和操作,如皮层D2功能柱的定位和D2功能柱内不同层神经元的定位等,结果和我室以前相关研究证明了此实验方案的可行性。     

Ontogenetic development of neural responses in the olfactory bulb of laboratory mice

Summary In laboratory mice (strain NMRI) the ontogenetic development of single unit activity in the olfactory bulb was investigated. From postnatal day 10 on, spontaneously active neurons were recorded with glass-microelectrodes, and their responses to olfactory stimuli were tested (butyric acid, geraniol, grass- and nest-odour).From day 10 to 13 only very few neurons were recordable (and most of these elements were too weak and were lost before being stimulated). At day 14 the number of recordable neurons increased rapidly, and by day 15 spontaneously active neurons reached adult level in terms of incidence and electric properties.There were 3 types of neurons: 1. respiration synchronous elements; 2. bursting neurons not correlated with respiration; 3. continuously, but randomly, firing elements (about 60% of all neurons). Reactions to odour stimuli (excitation, ca. 50%; inhibition, ca. 34%; complex reactions, ca. 12%; change in activity pattern, ca. 4%) occurred as soon as the cells were stable enough for testing. The reaction patterns showed no age specific differences; the duration of the responses varied from 100 ms to 100 s.In younger animals (P11–P14) the percentage of responses was slightly smaller (47%) than in the older ones (P30–P50; 64% response to olfactory stimulation). For some of the odours tested the proportion of responding cells differed depending on age (for instance grass odour evoked a response in 40% of the cells in young ones, but in 65% in adults).Abbreviations AP action potential - In interneuron - MTc mitral or tufted cell - P10 postnatal day 10     

Netrin1 is required for neural and glial precursor migrations into the olfactory bulb

Netrin1 (NTN1) deficiency in mouse brain causes defects in axon guidance and cell migration during embryonic development. Here we show that NTN1 is required for olfactory bulb (OB) development at late embryogenesis and at early postnatal stages to facilitate the accumulation of proper numbers of granular and glomerular neuron subtypes and oligodendrocytes into the OB. In addition to the analysis of Ntn1−/− mice we made tissue and neurosphere cultures to clarify the role of NTN1 in the anterior forebrain. We propose that a subset of neural progenitors/precursors requires NTN1 to efficiently enter the rostral migratory stream to migrate into the OB. The analysis of postnatal Ntn1−/− OBs revealed a reduction of specific types of interneurons which have been shown to originate from particular subregions of the lateral ventricle walls. Based on Ntn1 expression in ventral parts of the ventricle walls, we observed a decrease in the mainly ventrally derived type II interneurons that express calcium-binding proteins calretinin and calbindin. Instead, no change in the numbers of dorsally derived tyrosine hydroxylase expressing interneurons was detected. In addition to the specific reduction of type II interneurons, our results indicate that NTN1 is required for oligodendroglial migration into the OB. Furthermore, we characterised the Ntn1 expressing subpopulation of neurosphere-forming cells from embryonic and adult brain as multipotent and self-renewing. However, NTN1 is dispensable for the proliferation of neurosphere forming progenitor cells and for their differentiation.     

Comparison of social interaction and neural activation in the main olfactory bulb and the accessory olfactory bulb between Microtus mandarinus and Microtus fortis

To gain insight into the function of AOB and MOB during different social interaction and in different vole species,the behaviors and neural activation of the olfactory bulbs in social interactions of mandarin voles Microtus mandarinus and reed voles Microtus fortis were compared in the present research.Mandarin voles spent significantly more time attacking and sniffing their opponents and sniffing sawdust than reed voles.During same sex encounters,mandarin voles attacked their opponents for a significantly ...     

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     

Mechanism of migration of olfactory bulb interneurons

Neuroblasts in the subventricular zone of the walls of the lateral ventricle in the brain of young and adult rodents migrate into the olfactory bulb where they differentiate into local interneurons. These cells move closely associated with each other, forming chains without radial glial or axonal guidance. The migrating neuroblasts express PSA-NCAM on their surface and PSA residues are crucial for cell-cell interaction during chain migration. This migration occurs throughout the lateral wall of the lateral ventricle, where the precursors form an extensive network of chains. Cells remain organized as chains until they reach the olfactory bulb, where they disperse organized as chains until they reach the olfactory bulb, where they disperse radially as individual cells. Chain migration defines a novel form of neuronal precursor translocation which is based on homotypic interactions between cells.     

The effects of analgesic supplements on neural activity in the main olfactory bulb of the mouse

We evaluated ketoprofen, a nonsteroidal anti-inflammatory drug (NSAID), as an antinociceptive supplement to chloral hydrate anesthesia in mouse. Effects of ketoprofen on main olfactory bulb (MOB) neuronal spontaneous activity were investigated using extracellular recordings in mouse in vivo. These effects were compared with those of another nociceptive supplement, the mu-opioid agonist buprenorphine. Ketoprofen (100 or 200 mg/kg) did not significantly alter MOB single-unit spontaneous rates in either ICR or C57BL/6J mice. In contrast, buprenorphine, at doses of 0.02, 0.05, and 0.20 mg/kg, inhibited MOB neuronal spontaneous rates by 19%, 49%, and 57%, respectively. Neither drug altered the temporal patterning of single-unit spike trains, as measured by the interspike interval (ISI) coefficient of variation (CV). We also investigated the ability of ketoprofen and buprenorphine to induce antinociception in the anesthetized mouse. The electroencephalogram (EEG) was used to measure the anesthetic plane. Both ketoprofen and buprenorphine altered the EEG trace and ketoprofen altered the power spectrum in a manner consistent with deepening anesthesia. Lastly, when applied at the time of anesthesia induction, ketoprofen decreased the amount of chloral hydrate necessary to maintain a defined anesthetic plane during the rest of the experiment. These results suggest that ketoprofen induces antinociception under chloral hydrate anesthesia without significantly inhibiting spontaneous activity of MOB neurons. Ketoprofen is therefore suitable as an antinociceptive supplement to chloral hydrate anesthesia during in vivo electrophysiologic recordings of the mouse MOB.     

Forebrain projections of the pigeon olfactory bulb

The olfactory system of the pigeon (Columba livia) was examined. Our electrophysiological and experimental neuroanatomical (Fink-Heimer technique) data showed that axons from the olfactory bulb terminated in both sides of the forebrain. The cortex prepiriformis (olfactory cortex), the hyperstriatum ventrale and the lobus parolfactorius comprised the uncrossed terminal field. The crossed field included the paleostriatum primitivum and the caudal portion of the lobus parolfactorius, areas which were reached through the anterior commissure. In this report the relationships between areas that receive olfactory information and the possible roles that olfaction plays in the birds' behavior are discussed.     

Axon mis-targeting in the olfactory bulb during regeneration of olfactory neuroepithelium

During development, primary olfactory axons typically grow to their topographically correct target zone without extensive remodelling. Similarly, in adults, new axons arising from the normal turnover of sensory neurons essentially project to their target without error. In the present study we have examined axon targeting in the olfactory pathway following extensive chemical ablation of the olfactory neuroepithelium in the P2-tau:LacZ line of mice. These mice express LacZ in the P2 subpopulation of primary olfactory neurons whose axons target topographically fixed glomeruli on the medial and lateral surfaces of the olfactory bulb. Intraperitoneal injections of dichlobenil selectively destroyed the sensory neuroepithelium of the nasal cavity without direct physical insult to the olfactory neuron pathway. Primary olfactory neurons regenerated and LacZ staining revealed the trajectory of the P2 axons. Rather than project solely to their topographically appropriate glomeruli, the regenerating P2 axons now terminated in numerous inappropriate glomeruli which were widely dispersed over the olfactory bulb. While these errors in targeting were refined over time, there was still considerable mis-targeting after four months of regeneration.     

Two distinct channels of olfactory bulb output

Rhythmic neural activity is a hallmark of brain function, used ubiquitously to structure neural information. In mammalian olfaction, repetitive sniffing sets the principal rhythm but little is known about its role in sensory coding. Here, we show that mitral and tufted cells, the two main classes of olfactory bulb projection neurons, tightly lock to this rhythm, but to opposing phases of the sniff cycle. This phase shift is established by local inhibition that selectively delays mitral cell activity. Furthermore, while tufted cell phase is unperturbed in response to purely excitatory odorants, mitral cell phase is advanced in a graded, stimulus-dependent manner. Thus, phase separation by inhibition forms the basis for two distinct channels of olfactory processing.     

Simultaneous single unit recording in the mitral cell layer of the rat olfactory bulb under nasal and tracheal breathing

Odor perception depends on the odorant-evoked changes on Mitral/Tufted cell firing pattern within the olfactory bulb (OB). The OB exhibits a significant "ongoing" or spontaneous activity in the absence of sensory stimulation. We characterized this ongoing activity by simultaneously recording several single neurons in the mitral cell layer (MCL) of anesthetized rats and determined the extent of synchrony and oscillations under nasal and tracheal breathing. We recorded 115 neurons and found no significant differences in the mean firing rates between both breathing conditions. Surprisingly, nearly all single units exhibited a long refractory period averaging 14.4 ms during nasal respiration that was not different under tracheal breathing. We found a small incidence (2% of neurons) of gamma band oscillations and a low incidence (8.1%) of correlated firing between adjacent MCL cells. During nasal respiration, a significant oscillation at the respiratory rate was observed in 12% of cells that disappeared during tracheal breathing. Thus, in the absence of odorants, MCL cells exhibit a long refractory period, probably reflecting the intrinsic OB network properties. Furthermore, in the absence of sensory stimulation, MCL cell discharge does not oscillate in the gamma band and the respiratory cycle can modulate the firing of these cells.     

The influence of early odour experience on the neural response of the olfactory bulb in laboratory mice

Summary In mice (strain NMRI) the influence of olfactory rearing conditions on the ontogenetic development of the bulbar electroencephalogram (EEG) was investigated.The cages of control animals were perfused continually with filtered air, whereas in the three experimental groups geraniol was added to the atmosphere at different times (group G_0–13, from birth till day 13; group G_0–6, from birth till day 6; group G_6–12, from day 6 till day 12). At various ages the EEG of the bulbus olfactorius was studied by means of permanently implanted tungsten electrodes, and the neural response to nest odour and geraniol (10^–2 vol. %) was recorded.No differences were found between the groups regarding the overall development of the bulbar EEG, nor did the raising conditions affect the neural response to nest odour. However, in groups G_0–13 and G_6–12 a marked response to the odour of geraniol was recorded, while in the controls and the individuals that had experienced geraniol only during their first week of life, the bulbar response to this odourant did not differ from that obtained following stimulation with clean air. In the animals of group g_0–13, which were investigated as adults (day 70), the prominent geraniol response was still recordable 2 months after the last contact with the odour.These results indicate that odours experienced during a sensitive period in the nest evoke neuronal alterations in the olfactory system of the mouse that facilitate processing of a known odourant.     

A model of olfactory adaptation and sensitivity enhancement in the olfactory bulb

It has been suggested that the olfactory bulb, the first processing center after the sensory cells in the olfactory pathway, plays a role in olfactory adaptation, odor sensitivity enhancement by motivation and other olfactory psychophysical phenomena. In a mathematical model based on the bulbar anatomy and physiology, the inputs from the higher olfactory centers to the inhibitory cells in the bulb are shown to be able to modulate the response, and thus the sensitivity of the bulb to specific odor inputs. It follows that the bulb can decrease its sensitivity to a pre-existing and detected odor (adaptation) while remaining sensitive to new odors, or increase its sensitivity to interested searching odors. Other olfactory psychophysical phenomena such as cross-adaptation etc. are discussed as well.