Role of centrifugal projections to the olfactory bulb in olfactory processing

While there is evidence that feedback projections from cortical and neuromodulatory structures to the olfactory bulb are crucial for maintaining the oscillatory dynamics of olfactory bulb processing, it is not clear how changes in dynamics are related to odor perception. Using electrical lesions of the olfactory peduncle, sparing output from the olfactory bulb while decreasing feedback inputs to the olfactory bulb, we demonstrate here a role for feedback inputs to the olfactory bulb in the formation of odor-reward associations, but not for maintaining primary bulbar odor representations, as reflected by spontaneous odor discrimination.     

Pharmacological antagonism of mouse-killing behavior in the olfactory bulb lesion-induced killer rat

Representative agents from all of the major classes of drugs that have been reported to be selective antagonists of spontaneous mouse-killing behavior (i.e., antidepres-sants, antihistamines, anticholinergics, and stimulants) were tested for their ability to antagonize the mouse-killing response in rats that became killers following removal of the olfactory bulbs (O.B. lesion-induced killer rat) and in spontaneous killers. All of the drugs tested selectively antagonized the killing behavior of both spontaneous and lesion-induced mouse-killing rats. Several drugs (i.e., imipramine, amitriptyline, d-amphetamine, and chlorpheniramine) were found to be significantly less potent antagonists of mouse killing in the 0.6. lesioned rat as compared to spontaneous killers. Since all of the drugs that exhibited significant differences in activity between the two models have been shown to possess the ability to elevate norepinephrine levels at receptor sites in the brain, alterations in noradrenergic systems may account for the differences in sensitivity that were observed in this study. The possibility that there may be a common neural substrate for mouse killing in the two models is discussed.     

Adrenergic modulation of olfactory bulb circuitry affects odor discrimination

A rodent's survival depends upon its ability to perceive odor cues necessary to guide mate selection, sexual behavior, foraging, territorial formation, and predator avoidance. Arguably, the need to discriminate odor cues in a complex olfactory environment requires a highly adaptable olfactory system. Indeed, it has been proposed that context-dependent modulation of the initial sensory relay could alter olfactory perception. Interestingly, 40% of the adrenergic innervation from the locus coeruleus, fibers that are activated by contextual cues, innervates the first relay station in the olfactory system (the main olfactory bulb). Here we utilize restricted pharmacological inhibition of olfactory bulb noradrenergic receptors in awake-behaving animals. We show that combined blockade of alpha and beta adrenergic receptors does not impair two-odor discrimination behavior per se but does impair the ability to discriminate perceptually similar odors. Thus, contextual cues conveyed by noradrenergic fibers alter processing before the second synapse in the olfactory cortex, resulting in tuning of the ability to discriminate between similar odors.     

Bicuculline infusion into the accessory olfactory bulb facilitates the induction of maternal behavior in rats

The GABAA antagonist bicuculline, intracranially infused into the accessory olfactory bulb (AOB), facilitated the expression of maternal behavior (MB) in virgin Wistar female rats. Behavioral effects were observed 24 hours after infusion and were injection dependent. Pheromonal stimuli, generated by the pups, are thought to exert an inhibitory effect on vomeronasal nuclei involved in MB in virgin rats. The present study investigated the possibility that a decrement in AOB output, resulting from long-term compensatory synaptic changes to chronic bicuculline infusion, would facilitate the expression of MB. The implications of our findings for the mechanisms involved in the induction of MB and the maternal experience effect are discussed.     

The role of the dorsal and ventral hippocampus in olfactory working memory

Olfactory working memory and pattern separation for odor information was assessed in male rats using a matching-to-sample for odors paradigm. The odor set consisted of a five aliphatic acids with unbranched carbon chains that varied from two- to six-carbons in length. Each trial consisted of a sample phase followed by a choice phase. During the sample phase, rats would receive one of five different odors. Fifteen seconds later during the choice phase one of the previous odors was presented simultaneously side by side with a different odor that was based on the number of aliphatic acids that varied in the carbon chains from two- to six-carbons in length and rats were allowed to choose between the two odors. The rule to be learned in order to receive a food reward was to always choose the odor that occurred during the study phase. Odor separations of 1, 2, 3 or 4 were selected for each choice phase and represented the carbon chain difference between the study phase odor and the test phase odor. Once an animal reached a criterion of 80–90% correct across all temporal separations based on 40 trials, rats received a control, dorsal hippocampal, or ventral hippocampal lesion and were retested on the task. On postoperative trials, only the ventral hippocampal lesion group was impaired relative to both control and dorsal hippocampal groups groups. There were no effects on odor pattern separation. All groups of rats could discriminate between the odors. The data suggest that the ventral hippocampus, but not dorsal hippocampus, supports working memory for odor information.     

The role of taste and oral somatosensation in olfactory localization

Although there is only one set of olfactory receptors, odours are experienced as smells when sniffing things (e.g., sniffing a wine's bouquet) and as flavours when the olfactory stimulus is present in the mouth (e.g., drinking wine). How this location binding—external versus internal environment—is achieved is poorly understood. Experiment 1 employed a new procedure to study localization, which was then used to explore whether localization is primarily dependent upon simultaneous oral somatosensation. Experiment 2, using solutions of varying viscosity, and Experiment 3, using oral movement of varying vigour, revealed that sniffed odours are not localized to the mouth by somatosensation alone. Instead, Experiment 4 demonstrated that a tastant needs to be present and that increasing tastant concentration generates increasing oral localization. Experiment 5 found that this reliance upon gustation reflects the previously observed “confusion” that people show for taste and smell stimuli in the mouth. We suggest that this “confusion” reflects the gustatory system's superior ability to suppress olfactory attention, thus assisting flavour binding.     

Low-dimensional chaos maps learning in a model neuropil (olfactory bulb).

Quantification of a chaotic system can be made by calculating the correlation dimension (D2) of the data that the system generates (Packard et al., 1980). The D2 algorithm, however, requires stationarity of the generator, a feature that biological data rarely reflect (Mayer-Kress et al., 1988). So we developed the "point correlation dimension" (PD2), an algorithm that accurately tracks D2 in linked data of different dimensions (Carpeggiani et al., 1991). We now present a mathematical argument that, for stationary data, individual PD2s converge to D2 and we demonstrate that the algorithm rejects contributions made by bursts of noise. Data were obtained from the surface of the olfactory bulb of the conscious rabbit (64 electrodes, 640 Hz each, 1.3 sec epochs) before and after presentation of a novel or habituated odor. D2 could be calculated in only 1 of 10 novel-odor trials, whereas PD2 could be calculated in all. Both algorithms indicated that a novel odor evokes a spatially uniform dimensional increase. The PD2 uniquely exhibited the dimensional decreases that occur during inspiration and the gradients of mean dimension present during the nonstimulated control state. These control gradients remained unchanged without odor experience, but showed spatially specific PD2 increases following odor habituation. It is interpreted that, 1) the PD2 is sensitive, accurate, and appropriate for dimensional assessment of biological data, 2) that during analysis of unfamiliar information a single global process is transiently evoked in the neuropil, and 3) after experience multiple spatially specific processes tonically map the sites of learning.     

Low-dimensional chaos maps learning in a model neuropil (olfactory bulb)

Quantification of a chaotic system can be made by calculating the correlation dimension (D2) of the data that the system generates (Packard et al., 1980). The D2 algorithm, however, requires stationarity of the generator, a feature that biological data rarely reflect (Mayer-Kress et al., 1988). So we developed the “point correlation dimension” (PD2), an algorithm that accurately tracks D2 in linked data of different dimensions (Carpeggiani et al., 1991). We now present a mathematical argument that, for stationary data, individual PD2s converge to D2 and we demonstrate that the algorithm rejects contributions made by bursts of noise. Data were obtained from the surface of the olfactory bulb of the conscious rabbit (64 electrodes, 640 Hz each, 1.3 sec epochs) before and after presentation of a novel or habituated odor. D2 could be calculated in only 1 of 10 novel-odor trials, whereas PD2 could be calculated in all. Both algorithms indicated that a novel odor evokes a spatially uniform dimensional increase. The PD2 uniquely exhibited the dimensional decreases that occur during inspiration and the gradients of mean dimension present during the nonstimulated control state. These control gradients remained unchanged without odor experience, but showed spatially specific PD2 increases following odor habituation. It is interpreted that, 1) the PD2 issensitive, accurate, and appropriate for dimensional assessment of biological data, 2) that during analysis of unfamiliar information a singleglobal process is transiently evoked in the neuropil, and 3) after experience multiplespatially specific processes tonically map the sites of learning. Grant Support: National Institutes of Health, HL 31164 and NS27745     

Odor enrichment increases interneurons responsiveness in spatially defined regions of the olfactory bulb correlated with perception

Odor enrichment enhances rats’ ability to discriminate between chemically similar odorants. We show here that this modulation of olfactory perception is accompanied by increases in the density of local inhibitory interneuron expressing Zif268 in response to olfactory stimuli. These changes depend on the overlap of the olfactory bulb activation patterns induced by the enrichment odorants with those induced by the testing odorants, in a manner similar to changes in perception. Moreover, we show that enrichment leads to an alteration of the pattern of Zif268 expression, dependent on the odors used for the enrichment indicating a restructuring of odor representation in the olfactory bulb.     

pCREB in the neonate rat olfactory bulb is selectively and transiently increased by odor preference-conditioned training

Early olfactory preference learning in rat pups occurs when novel odors are paired with tactile stimulation, for example stroking. cAMP-triggered phosphorylation of cAMP response element binding protein (pCREB) has been implicated as a mediator of learning and memory changes in various animals (Frank and Greenberg 1994). In the present study we investigate whether CREB is phosphorylated in response to conditioned olfactory training as might be predicted given the proposed role of the phosphorylated protein in learning. On postnatal day 6, pups were trained for 10 min using a standard conditioned olfactory learning paradigm in which a conditioned stimulus, Odor, was either used alone or paired with an unconditioned stimulus, Stroking (using a fine brush to stroke the pup). In some instances stroking only was used. The pups were sacrificed at 0, 10, 30, or 60 min after the training. Using Western blot analysis, we observed that the majority of olfactory bulbs in conditioned pups (Odor + Stroking) had a greater increase in pCREB activation at 10 min after training than pups given nonlearning training (Odor only or Stroking only). The phosphorylated protein levels were low at 0 min and at 60 min after training. This is in keeping with the slightly delayed and short-lived activation period for this protein. The localization of pCREB increases within the olfactory bulb as seen by immunocytochemistry. Naive pups were not exposed to odor or training. There was a significantly higher level of label in mitral cell nuclei within the dorsolateral quadrant of the bulb of pups undergoing odor-stroke pairing. No significant differences were observed among nonlearning groups (Naive, Odor only, or Stroking only) or among any training groups in the granule or periglomerular cells of the dorsolateral region. The localized changes in the nuclear protein are consistent with studies showing localized changes in the bulb in response to a learned familiar odor. The present study demonstrates that selective increases in pCREB occur as an early step following pairing procedures that normally lead to the development of long-term olfactory memories in rat pups. These results support the hypothesized link between pCREB and memory formation.     

The role of the accessory and main olfactory systems in maternal behavior of the primiparous rat

The objective of this study was to analyze the respective roles of the main and accessory olfactory systems in the development of maternal behavior in the primiparous Wistar rat. Females underwent one of the following treatments: vomeronasal nerve section (VN), irrigation of nasal cavities with 5% ZnSO4 solution (ZN), surgical control, saline irrigation control, and normal control. Surgical or first irrigation were done before mating occurred. Irrigations were done every 7 days thereafter. The dams and their litters were observed from the day the litter was born (Day 1) through Day 16. Pup weights and temperatures were recorded daily. Home cages were checked daily for changes in nest location and number of times pups were found out of the nest. Retrieving tests were conducted on Days 4, 7, 10, and 13. The following behavioral items were observed: number of pup retrievals , number of times mother nosed or licked pups, percentage of litter returned to nest by end of test, dam self-grooming, dam climbing or rising, and dam digging or burrowing in shavings. The VN dams and their litters were not significantly different from the control dams and their litters on any of the measures taken. The ZN dams and their litters were not significantly different from their controls on all measures except for pup body temperature which was slightly lower from Day 13 through day 16 and pup body weight which was slightly lower from Day 12 through Day 16. Since these differences are very small, they do not seem to indicate a serious deficiency in maternal behavior. The results indicate that adequate maternal behavior develops with either of the two systems intact.     

A specific role for the human amygdala in olfactory memory

The medial temporal lobe is known to play a role in the processing of olfaction and memory. The specific contribution of the human amygdala to memory for odors has not been addressed, however. The role of this region in memory for odors was assessed in patients with unilateral amygdala damage due to temporal lobectomy (n = 20; 11 left, 9 right), one patient with selective bilateral amygdala damage, and in 20 age-matched normal controls. Fifteen odors were presented, followed 1 h later by an odor-name matching test and an odor-odor recognition test. Signal detection analyses showed that both unilateral groups were impaired in their memory for matching odors with names, these patients were not significantly impaired on odor-odor recognition. Bilateral amygdala damage resulted in severe impairment in both odor-name matching as well as in odor-odor recognition memory. Importantly, none of the patients were impaired on an auditory verbal learning task, suggesting that these findings reflect a specific impairment in olfactory memory, and not merely a more general memory deficit. Taken together, the data provide neuropsychological evidence that the human amygdala is essential for olfactory memory.     

Central synaptic mechanisms underlie short-term olfactory habituation in Drosophila larvae

Naive Drosophila larvae show vigorous chemotaxis toward many odorants including ethyl acetate (EA). Chemotaxis toward EA is substantially reduced after a 5-min pre-exposure to the odorant and recovers with a half-time of ～20 min. An analogous behavioral decrement can be induced without odorant-receptor activation through channelrhodopsin-based, direct photoexcitation of odorant sensory neurons (OSNs). The neural mechanism of short-term habituation (STH) requires the (1) rutabaga adenylate cyclase; (2) transmitter release from predominantly GABAergic local interneurons (LNs); (3) GABA-A receptor function in projection neurons (PNs) that receive excitatory inputs from OSNs; and (4) NMDA-receptor function in PNs. These features of STH cannot be explained by simple sensory adaptation and, instead, point to plasticity of olfactory synapses in the antennal lobe as the underlying mechanism. Our observations suggest a model in which NMDAR-dependent depression of the OSN-PN synapse and/or NMDAR-dependent facilitation of inhibitory transmission from LNs to PNs contributes substantially to short-term habituation.     

Effects of olfactory bulb ablation on cardiac and ventilatory arousal responses and their habituation in the goldfish Carassius auratus

The effects of olfactory bulb ablation on the cardiac and ventilatory arousal responses to the onset of illumination and habituation of these responses were investigated in goldfish. Bulbectomy did not effect the magnitude of response on novel stimulus presentation. Normal, sham operated, and olfactory bulb-ablated animals showed similar rates of habituation. These results suggest that deficits in feeding and sexual behavior in goldfish are due to the loss of specific olfactory influences on lower brain centers and not due to a decrease in general responsiveness.     

The role of sparsely distributed representations in familiarity recognition of verbal and olfactory materials

We present the generalized signal detection theory (GSDT), where familiarity is described by a sparse binomial distribution of binary node activity rather than by normal distribution of familiarity. Items are presented in a distributed representation, where each node receives either noise only, or signal and noise. An old response (i.e., a “yes” response) is made if at least one node receives signal plus noise that is larger than the activation threshold, and item variability is determined by the distribution of activated nodes as the threshold is varied. A distinct representation leads to better performance and a lower ratio of new to old item variability, than a more distributed and less distinct representations. Here we apply the GSDT to empirical data on verbal and olfactory memory and suggest that verbal memory relies on a distinct neural item representation, whereas olfactory memory has a fuzzy neural representation leading to poorer memory and inducing a larger ratio of new to old item variability.     

Interspecific aggression and reactivity in rats: Effects of selective raphe lesions and additional olfactory bulb ablation

Large depletion of brain 5 HT has been shown to induce mouse-killing behavior in the rat. Selective lesions of the raphe nuclei have been investigated in order to determine whether the various components of the 5 HT system exert some specific control over this aggressive behavior. Electrolytic lesions of the dorsal or the median raphe nucleus do not induce mouse killing, whereas combined lesions of these nuclei elicit this behavior in about 40% of naive rats. Consequently, it appears that serotonergic neurons originating in the dorsal and median raphe nuclei work synergistically in mediating inhibitory control over mouse-killing behavior. Loco-motor activity is increased in novel environments by each of the selective lesions and to a larger extent by combined raphe lesions; 24 hours activity in resting conditions is unchanged during the light period, and increased during the dark period of the daily cycle by the various lesions. As it has been shown previously that hyper-activity in response to novelty following raphe lesions is not directly related to the 5 HT decrease in the brain, it appears that interspecific aggression and motor responsiveness must not be dependent on the same neural substrate within the raphe nuclei. The raphe lesions do not facilitate the elicitation of mouse killing by further olfactory bulb ablations, in contrast to earlier results where bulbectomy facilitated the induction of this behavior by raphe lesions.     

Paradoxical olfactory function in combat Veterans: The role of PTSD and odor factors

Stress- and trauma-related disorders, including posttraumatic stress disorder (PTSD), are characterized by an increased sensitivity to threat cues. Given that threat detection is a critical function of olfaction and that combat trauma is commonly associated with burning odors, we sought a better understanding of general olfactory function as well as response to specific trauma-related (i.e. burning) odors in combat-related PTSD. Trauma-exposed combat Veterans with (n = 22) and without (n = 25) PTSD were assessed for general and specific odor sensitivities using a variety of tools. Both groups had similar general odor detection thresholds. However, the combat Veterans with PTSD, compared to combat Veterans with comparable trauma exposure but without PTSD, had increased ratings of odor intensity, negative valence, and odor-triggered PTSD symptoms, along with a blunted heart rate in response to burning rubber odor. These findings are discussed within the context of healthy versus pathological changes in olfactory processing that occur over time after psychological trauma.