Unilateral lesions of the olfactory tubercle modifying general arousal effects in the rat olfactory bulb.

The centrifugal control exerted by different arousal states on the rat olfactory bulb was investigated. The olfactory tubercle was unilaterally coagulated with either 1 mA or 3 mA current. The vigilance state parameters and multiunit mitral cell activity were recorded in freely moving rats, stimulated either by their usual food odor or by isoamyl acetate, in a hungry or a satiated state. In each animal, a unilateral lesion affected resting activity and the relative proportion of positive (excitatory) and negative (inhibitory) responses in the same way in both olfactory bulbs; these effects were proportional to the extent of the lesion. In wakefulness, a nutritional modulation of the bulb responses for food odor existed in spite of a slight decrease in the general arousal level. In slow wave sleep (SWS), when compared to a control group, the rats with lesions showed an increase of neocortical desynchronization induced by olfactory stimulation, and a large decrease of mitral cell excitability. Inhibition of the olfactory input, which normally develops during SWS, could involve mainly mesencephalic neurons reaching the olfactory tubercle and the bulb via the ventral part of the medial forebrain bundle.     

Modulation of olfactory learning in young rats through intrabulbar GABA(B) receptors

After training with an odour paired with foot shock on postnatal day 11, rat pups show an aversion to the odour in testing on postnatal day 12. The mechanisms underlying this aversive olfactory learning involve disinhibition of mitral/tufted cells in the olfactory bulb by the somatosensory stimulation-induced activation of centrifugal noradrenergic fibres originating in the locus coeruleus. The activity of mitral/tufted cells is regulated through gamma-aminobutyric acidA (GABA(A)) receptors in the external plexiform layer and GABA(B) receptors in the glomerular layer. We have previously presented that aversive olfactory learning in young rats is modulated through GABA(A) receptors in the olfactory bulb. In the present study we examined the consequence of manipulating GABA(B) receptors in the olfactory bulb during training. Baclofen, a GABA(B) receptor agonist when infused into the olfactory bulb during the pairing of an odour with foot shock, prevented aversive olfactory learning in a dose-dependent manner. Infusion of saclofen, a GABA(B) receptor antagonist, during training with a citral odour in the absence of foot shock produced aversive responses not only to the odour, but also to strange odours (benzaldehyde and vanillin) not previously presented. Such olfactory aversions were observed even if saclofen was infused without odour exposure. These results suggest that olfactory learning in young rats is modulated through GABA(B) receptors in the olfactory bulb.     

Ascending olfactory information and centrifugal influxes contributing to a nutritional modulation of the rat mitral cell responses

A nutritional modulation of electrical mitral cell multiunit responses was studied in three groups of rats, with either a unilateral section of the olfactory peduncle (OP) or of the lateral olfactory tract (LOT), or with unilaterally damaged olfactory mucosa (zinc sulphate treatment). The control and lesion-side activity was chronically recorded in the bulbs of hungry and satiated animals receiving series of 10 identical stimulations with a food odor and odors non-associated to nutrition. Patterns of positive, negative and null responses were thus collected.

In the control-side bulbs of the LOT and OP groups, as in intact animals, the percentage of positive responses was maximal in hungry rats receiving food odor, and minimal in satiated rats receiving isoamyl acetate, as a result of the nutritional modulation of responses.

In the lesion-side bulbs of the LOT group, activation increased irrespective of the nutritional state of the animal and the nutritional meaning of the odorant. This shift was reproduced in the lesion-side bulbs of the OP group. In these animals, no nutritional modulation was observed, an effect ascribed to the disruption of activating fibers in the anterior limb of the anterior commissure (AAC).

The zinc sulphate treated animals displayed a lack of olfactory responses in the treated-side bulbs, and no response modulation in the control-side bulbs, where the percentage of positive responses for non-alimentary odors was slightly increased, presumably as a consequence of the suppression of interbulbar inhibition. The results are discussed in terms of the quantity of olfactory information necessary for the centrifugal nutritional modulation to be released.

The neuronal circuits subserving these various effects in the bulb are considered.     

The coding of odour-intensity in the honeybee antennal lobe: local computation optimizes odour representation

We investigated strategies involved in odour intensity coding by the primary olfactory centre of insects, the antennal lobe (AL), the structural and functional analogue of the olfactory bulb. Using calcium imaging in the honeybee, we simultaneously measured the projection neuron output responses and a compound signal dominated by receptor neuron input in identified olfactory glomeruli to odours spanning seven log units of concentration. A comparison of the two processing levels indicates that the intercellular computation within the AL modulates and contrast-enhances the primary olfactory signals. As a result the AL network optimizes the olfactory code: odour representation is improved at lower concentrations, the relative activity of olfactory glomeruli allows encoding odour quality over up to four log-unit concentrations, and odour-intensity is reliably represented in the overall excitation across AL.     

Biological complexity and adaptability of simple mammalian olfactory memory systems

Chemosensory systems play vital roles in the lives of most mammals, including the detection and identification of predators, as well as sex and reproductive status and the identification of individual conspecifics. All of these capabilities require a process of recognition involving a combination of innate (kairomonal/pheromonal) and learned responses. Across very different phylogenies, the mechanisms for pheromonal and odour learning have much in common. They are frequently associated with plasticity of GABA-ergic feedback at the initial level of processing the chemosensory information, which enhances its pattern separation capability. Association of odourant features into an odour object primarily involves anterior piriform cortex for non-social odours. However, the medial amygdala appears to be involved in both the recognition of social odours and their association with chemosensory information sensed by the vomeronasal system. Unusually not only the sensory neurons themselves, but also the GABA-ergic interneurons in the olfactory bulb are continually being replaced, with implications for the induction and maintenance of learned chemosensory responses.     

Auditory arousal responses and thresholds during REM and NREM sleep of sleepwalkers and controls

BackgroundIt has been suggested that sleepwalkers are more difficult to awaken from sleep than are controls. However, no quantified comparisons have been made between these two populations. The main goal of this study was to assess arousal responsiveness via the presentation of auditory stimuli (AS) in sleepwalkers and controls during normal sleep and recovery sleep following sleep deprivation.MethodsTen adult sleepwalkers and 10 age-matched control subjects were investigated. After a screening night, participants were presented with AS during slow-wave sleep (SWS), REM, and stage 2 sleep either during normal sleep or daytime recovery sleep following 25 h of sleep deprivation. The AS conditions were then reversed one week later.ResultsWhen compared to controls sleepwalkers necessitated a significantly higher mean AS intensity (in dB) to induce awakenings and arousal responses during REM sleep whereas the two groups’ mean values did not differ significantly during SWS and stage 2 sleep. Moreover, when compared to controls sleepwalkers had a significantly lower mean percentage of AS that induced arousal responses during REM sleep while the opposite pattern of results was found during SWS.ConclusionsThe data indicate that sleepwalkers have a higher auditory awakening threshold than controls, but only for REM sleep. These findings may reflect a compensatory mechanism of the homeostatic process underlying sleep regulation during sleepwalkers’ REM sleep in reaction to their difficulties maintaining consolidated periods of NREM sleep.     

Expression of c-fos in the main olfactory bulb of neonatal rabbits in response to garlic as a novel and conditioned odour

Expression of c-Fos was examined in the olfactory bulbs of 3-day-old rabbits after they had been presented with the odour of garlic as a novel stimulus, as a learned odour, or during conditioning, and this expression compared with baseline levels in non-stimulated controls. Exposure to garlic odour resulted in substantial and widespread increases in c-Fos expression in the olfactory bulbs of all animals. However, although conditioned pups showed a specific behavioural response to the learned garlic odour, neither the amount nor pattern of c-Fos expression differed compared to pups exposed to garlic as a novel odour. The odour-induced expression of c-Fos was not well localised, although there was a significant increase in the number of granule cells expressing c-Fos in the ventrolateral region of the bulb. These results support previous reports that the response to odours in the olfactory bulb of new-born animals is not as spatially distinct as that in adults. Nevertheless, the immature olfactory system of these young animals is clearly capable of very specific odour learning.     

Effect of local 5,6-dihydroxytryptamine on the rat olfactory bulb responsiveness during wakefulness and sleep

This study investigated a possible participation of the centrifugal serotonergic (5-HT) innervation of the olfactory bulb (OB) in the control of the multiunit mitral cell responsiveness in behaving rats. A bilateral injection of 5,6-dihydroxytryptamine solution (5,6-DHT) into the OB induced in this structure an average 70% reduction in the level of endogenous serotonin. Control and treated animals were habituated to eat a single 2 h daily meal. Recording sessions were performed either after a 22 h fasting period or just after the meal. The summated multiunit mitral cell activity and vigilance state parameters were recorded in the absence of and during repeated stimulation by puffs of food odour and isoamyl acetate. The results showed that the 5,6-DHT treatment did not modify significantly previously established centrifugal controls exerted at the OB level: (1) the selective enhancement of the mitral cell responsiveness to food odour occurring in waking food-deprived animals; (2) the inhibition of the olfactory input during slow wave sleep. However, the considered 5-HT projections could mediate some inhibitory influence on mitral cell activity during wakefulness only. Finally, the 5-HT innervation of the OB did not seem to be involved in basic mechanisms of olfactory recognition.     

Transmission and integration of biologically meaningful olfactory information after bilateral transection of the lateral olfactory tract in the rat

The contribution of the olfactory inputs conveyed by the lateral olfactory tract (LOT) to the central olfactory areas in the onset of behavioral and electrophysiological responses i.e. multiunit activity of mitral cells was studied in rats which were submitted to a bilateral transection of LOT. The characteristic emotional reactions elicited in sham-operated rats by biologically meaningful odorants--odors of predator or of conspecific--were no longer observed after such lesion. At the olfactory bulb level, the differential habituation of mitral cell electrical responses according to the biological meaning of the stimuli disappeared in the rats with a bilateral section of LOT. However the awaking influence of the odorants when stimulations occurred during slow wave sleep remained unchanged: all the rats were more often awakened by the odor of predator than by the other stimuli. On the other hand, an inhibitory centrifugal influence of LOT on mitral cell electrical responses was noted in rats with a unilateral transection of LOT. The results are discussed in relation to the two olfactory pathways (lateral and medial). During wakefulness, LOT seems essential to the olfactory information processing; in slow wave sleep, the medial olfactory pathways appear to mediate olfactory discrimination and to elicit adapted arousal.     

Spatiotemporal representations in the olfactory system

A complete understanding of the mechanisms underlying any kind of sensory, motor or cognitive task requires analysis from the systems to the cellular level. In olfaction, new behavioural evidence in rodents has provided temporal limits on neural processing times that correspond to less than 150ms--the timescale of a single sniff. Recent in vivo data from the olfactory bulb indicate that, within each sniff, odour representation is not only spatially organized, but also temporally structured by odour-specific patterns of onset latencies. Thus, we propose that the spatial representation of odour is not a static one, but rather evolves across a sniff, whereby for difficult discriminations of similar odours, it is necessary for the olfactory system to "wait" for later-activated components. Based on such evidence, we have devised a working model to assess further the relevance of such spatiotemporal processes in odour representation.     

Maternal Odours Induce Fos in the Main But Not the Accessory Olfactory Bulbs of Neonatal Male and Female Ferrets

Previous research demonstrated that exposing gonadectomized adult ferrets to odours in oestrous female bedding induced nuclear Fos-immunoreactivity (Fos-IR; a marker of neuronal activity) in the main as opposed to the accessory olfactory system in a sexually dimorphic fashion, which was further augmented in both sexes by treatment with testosterone propionate. Ferrets are born in an altricial state and presumably use maternal odour cues to locate the nipples until the eyes open after postnatal (P) day 23. We investigated whether maternal odours augment neuronal Fos preferentially in the main versus accessory olfactory system of neonatal male and female ferret kits. Circulating testosterone levels peak in male ferrets on postnatal day P15, and mothers provide maximal anogenital stimulation (AGS) to males at this same age. Therefore, we assessed the ability of maternal odours to augment Fos-IR in the accessory olfactory bulb (AOB), the main olfactory bulb (MOB) and other forebrain regions of male and female ferret kits on P15 and investigated whether artificial AGS (provided with a paintbrush) would further enhance any effects of maternal odours. After separation from their mothers for 4 h, groups of male and female kits that were placed for 1.5 h with their anaesthetized mother had significantly more Fos-IR cells in the MOB granule cell layer and in the anterior-cortical amygdala, but not in the AOB cell layer, compared to control kits that were left on the heating pad. Artificial AGS failed to amplify these effects of maternal odours. Maternal odours (with or without concurrent AGS) failed to augment neuronal Fos-IR in medial amygdaloid and hypothalamic regions that are activated in adult ferrets by social odours. In neonatal ferrets of both sexes, as in adults, socially relevant odours are detected by the main olfactory epithelium and initially processed by the MOB and the anterior-cortical amygdala. In neonates, unlike adults, medial amygdaloid and hypothalamic neurones either do not respond to these inputs or respond in a manner that fails to induce Fos expression.     

The infralimbic cortical area commands the behavioral and vegetative arousal during appetitive behavior in the rat

The infralimbic cortical area is a good candidate to send processed motivational signals to initiate the arousing and autonomic responses that characterize appetitive behaviors. To test this hypothesis we enticed hungry rats with food while assessing locomotion (as an index of arousal level) and temperature responses, and evaluated Fos immunoreactivity (IR) in the infralimbic area and in subcortical nuclei involved in thermoregulation or arousal. We also recorded from single infralimbic neurons in freely moving rats while enticing them with food. We found that 83% of infralimbic neurons were excited or inhibited by feeding and, in particular, that 33% of infralimbic neurons increased their discharge rate during food enticing. Intact rats showed increased Fos IR in the infralimbic area, as well as in many other cortical areas. The excitotoxic lesion of the infralimbic cortex abolished the arousing and hyperthermic responses observed in intact rats, as well as the expression of Fos IR in the ascending arousal system and subcortical thermoregulatory regions. We conclude that the infralimbic area plays a central role in implementing behavioral arousing and thermal responses during an appetitive behavior.     

The thalamus participates in the regulation of the sleep-waking cycle. A clinico-pathological study in fatal familial thalamic degeneration

Loss of slow-wave sleep (SWS) and abnormal REM sleep behaviour were associated with a lack of vegetative and endocrine circadian rhythms in a patient with fatal familial thalamic degeneration. Physiological EEG patterns of SWS (spindles, K complexes, delta activity) were absent. EEG fast rhythms could not be induced by barbiturate or benzodiazepine administration. RO 15-1788, a benzodiazepine antagonist, induced arousal and awakened the patient from coma. Pathological findings were severe neuronal loss restricted to the anterior and dorso-medial thalamic nuclei. The clinical and electrophysiological data, together with the pathological correlates, emphasize the role played by the thalamus in the regulation of the sleep-waking and other circadian cycles.     

Synaptic plasticity in the hippocampus is modulated by behavioral state

The possible influence of the sleep-waking cycle on evoked neurotransmission and on the induction of long-term potentiation (LTP) and depression (LTD) was studied in the perforant path-granule cell system. Freely moving rats received a high-frequency stimulus train (8 bursts at 400 Hz) during slow-wave sleep (SWS), rapid eye movement (REM) sleep, and a still-alert (SAL) behavioral state. Trains applied during SAL and REM reliably elicited LTP of the excitatory postsynaptic potential (EPSP) slope, population spike height, and spike onset latency. Granule cell excitability was also enhanced, as indicated by a leftward shift of the EPSP-population spike (E-S) relation. In contrast, tetanization in SWS rarely produced 'classical' LTP and often failed to elicit any lasting change in field potentials. Furthermore, the following types of E-S change occurred almost exclusively after tetanization in SWS: (1) LTP of the EPSP accompanied by depression of the population spike, and (2) E-S potentiation without a change in EPSP. When LTP occurred, however, its magnitude was independent of the animal's behavioral state at the time of the train. In agreement with previous reports, the efficacy of low-frequency neurotransmission varied with behavioral state. A modulation index (MI) was introduced to quantify the difference between field potentials evoked in SAL and SWS. Interestingly, both the occurrence and magnitude of LTP were related to the strength of the MI, as determined in each rat before the train. After trains, the state-dependent modulation of transmission was maintained and was superimposed on LTP and LTD. The results suggest that synaptic plasticity is dynamically modulated during the sleep-wakefulness cycle.     

Cholinergic mechanisms involved in cortical activation during arousal.

Spontaneous and evoked cortical electrical activity of the post-central gyrus was studied in 5 unparalyzed, unanesthetized monkeys during slow-wave sleep (SWS) and wakefulness (W), before and after the administration of a muscarinic anticholinergic agents, hyoscine. It was found that hyoscine reproduces the effect of SWS: (1) on spontaneous EEG activity and single unit discharges of the somatosensory cortes without any concomitant behavioral sleep; and (2) on surface evoked potentials and reactivity of cortical neurons to peripheral electrical stimulation. Short episodes of EEG desynchronization were noted in the alert state after hyoscine suggesting the existence of a phasic activating system unblocked by hyoscine. These observations support the concept of an EEG-behavior dissociation produced by muscarinic anticholinergic agents and extend this concept to single neuron activity. These observations also lead to the conclusion that tonic EEG activation during arousal may be cholinergic at the cortical level even though other neurotransmitters may be involved.     

Locus coeruleus activation modulates firing rate and temporal organization of odour-induced single-cell responses in rat piriform cortex

Piriform cortex (PCx) is the primary cortical projection region for olfactory information and has bidirectional monosynaptic connections with olfactory bulb and association cortices. PCx neurons display a complex receptive field, responding to odours rather than their molecular components, suggesting that these neurons are involved in higher order olfactory processing. Neuromodulators, especially noradrenaline (NA), have important influences on sensory processing in other cortical regions and might be responsible for the plasticity observed in PCx during learning. The present study is the first attempt to examine in vivo the actions of NA on sensory responses in the PCx. Stimulation of the noradrenergic nucleus locus coeruleus (LC) was used to induce release of NA in the forebrain in urethane-anaesthetized rats. Extracellular recording of single units was made simultaneously in anterior and posterior PCx. The responses to an odour stimulus were measured over 25 trials. Twenty-five subsequent odour presentations were preceded by stimulation of the ipsilateral LC through a bipolar electrode, previously placed in the LC under electrophysiological control. This priming stimulation modified the activity of 77 of the 135 recorded neurons. For most cells, LC stimulation enhanced cortical responses to odour in terms of both spike count and temporal organization, with some differential effects in anterior and posterior regions. These results are the first to show enhancement of sensory responses in the olfactory cortex by LC activation. Spontaneous activation of LC neurons such as occurs during learning could serve to enhance olfactory perception and promote learning.     

Spontaneous and odour evoked activity in single avian olfactory bulb neurones

Extracellular single unit recordings were made from various depths in the left olfactory bulb of ten anaesthetised, freely breathing adult hens (Gallus domesticus) using glass insulated tungsten microelectrodes. The 66 spontaneously active neurons recorded had widely variable firing rates (mean 4.9 spikes/s, range 0.1-32.4 spikes/s) and variable temporal firing patterns (regular, bursting and random discharge). Interspike interval histograms were constructed for each unit and tested for goodness of fit to theoretical distributions. The activity of 23 units fitted gamma distributions, six units fitted lognormal distributions, three units fitted Weibull distributions, one unit fitted an exponential distribution and 11 units had bimodal distributions. Responses of some units to odour stimuli (Clove oil, Geraniol, Limonene and Ammonia all at 10% vapour saturation) delivered directly to the olfactory epithelium were examined. Odour stimulation modified spontaneous activity in 29 of the 44 units tested, causing either inhibition (56%) or excitation (44%) of firing. Of the 35 units stimulated with more than one odour, 15 responded to multiple stimuli, showing excitation or inhibition only or both inhibition and excitation, depending on the odour applied. Ammonia most commonly elicited a response (70% of applications) and all the odours were capable of inducing both inhibition and excitation of spontaneous firing. Examination of transverse sections of adult hen olfactory bulb in the region corresponding to the recording sites allowed unit recording depth to be related to cellular layers. There was some evidence of different neurone properties in each bulb layer. The spontaneous activity and odour responses observed resemble those seen in other vertebrate groups and the firing rates observed are between those previously reported for mammals and reptiles. This study provides detailed physiological evidence for a well-developed functional olfactory system in an avian species.     

Detect, Reject, Focus: The Role of Satiation and Odor Relevance in Cross-Modal Attention

Visual task performance has been shown to be affected differentially based on exogenous attentional demands from trigeminal odorants (Michael et al. Behav Neurosci 119:708–715, 2005). To test the exogenous influences of other biologically relevant characteristics of odorants, hungry and satiated undergraduates completed a visual search task in the presence of an odor (popcorn, jasmine, or unscented). Results showed that popcorn seemed more intense to hungry participants than those who were satiated. Reaction time results generally followed the pattern of most visual search research; significant effects were observed for feature complexity, distracter field size, and the interaction between complexity and distracter field size (Forster and Lavie J Exp Psychol 14:73–83, 2008; Itti and Koch Vision Res 40:1489–1506, 2000; Kumada Vision Res 50:1402–1413, 2010; Treisman and Gelade Cogn Psychol 12:97–136, 1980). However, olfactory group and hunger level also influenced reaction times, in that satiated participants were faster in low perceptual load (single shared feature, small set-size) conditions than hungry participants. Results suggest that olfactory attention is in a constant state of environmental monitoring for salient odors that uses resources from a shared pool. Fewer resources seem to be used when an odor with decreased saliency is detected, resulting in attentional benefits for information coming in from the visual system. These results generally support the modified Perceptual Load Theory of cross-modal attention (Tellinghuisen and Nowak Percept Psychophys 65:8717–8728, 2003) in which available shared attentional resources can be used to inhibit distracters to a visual task from other sensory modalities.     

Electrophysiological responses of rat olfactory tubercle neurons to biologically relevant odours

Biologically relevant odours were used to stimulate olfactory tubercle neurons in anaesthetized male rats. Among 120 recorded neurons, 118 showed spontaneous activity (mean firing rate, 15.0 ± 1.4 spikes/s). Ninety-eight neurons were exposed to at least one of the four following odour sources: an empty vial, or a vial containing food pellets (familiar odour), a sample of oestrous rat faeces (conspecific sexual odour), or a sample of male fox faeces (predator odour). The proportion of neurons responding with a change in activity was significantly linked to the odour applied. Repetition of the stimulation with the same odour elicited the same activity change. Between 50 and 70% of neuronal activity changes were not accompanied by respiration changes. Fifty-six neurons were exposed successively to all four odours, and 38 of them showed an activity change in response to at least one. The response of a neuron to an odour was not affected by its response to the previous one, and no neuron responded in the same manner to all odours. Conversely, no odour elicited a unique response in this population of neurons. However, the proportions of excited, inhibited and insensitive neurons depended significantly on the odour applied, suggesting that the recruitment of olfactory tubercle neurons is directly dependent on the biological significance of the odour.