Activation of olfactory and trigeminal cortical areas following stimulation of the nasal mucosa with low concentrations of S(-)-nicotine vapor--an fMRI study on chemosensory perception

Applied to the nasal mucosa in low concentrations, nicotine vapor evokes odorous sensations (mediated by the olfactory system) whereas at higher concentrations nicotine vapor additionally produces burning and stinging sensations in the nose (mediated by the trigeminal system). The objective of this study was to determine whether intranasal stimulation with suprathreshold concentrations of S(-)-nicotine vapor causes brain activation in olfactory cortical areas or if trigeminal cortical areas are also activated. Individual olfactory detection thresholds for S(-)-nicotine were determined in 19 healthy occasional smokers using a computer-controlled air-dilution olfactometer. Functional magnetic resonance images were acquired using a 1.5T MR scanner with applications of nicotine in concentrations at or just above the individual's olfactory detection threshold. Subjects reliably perceived the stimuli as being odorous. Accordingly, activation of brain areas known to be involved in processing of olfactory stimuli was identified. Although most of the subjects never or only rarely observed a burning or painful sensation in the nose, brain areas associated with the processing of painful stimuli were activated in all subjects. This indicates that the olfactory and trigeminal systems are activated during perception of nicotine and it is not possible to completely separate olfactory from trigeminal effects by lowering the concentration of the applied nicotine. In conclusion, even at low concentrations that do not consistently lead to painful sensations, intranasally applied nicotine activates both the olfactory and the trigeminal system.     

Thermal and nociceptive sensations from menthol and their suppression by dynamic contact

It was recently found that cooling the skin to temperatures as mild as 25-30 degrees C can induce nociceptive sensations (burning, stinging or pricking) that are strongly suppressed by dynamic contact between the thermode and skin (contact suppression). Here we investigated whether nociceptive sensations produced by menthol can be similarly suppressed. In the first experiment subjects rated the intensity of cold and burning/stinging/pricking sensations before and after application of 10% l-menthol to the forearm. Ratings were compared at resting skin temperature ( approximately 33 degrees C) and at 28, 24, or 20 degrees C during static or dynamic contact cooling via a Peltier thermode. At resting skin temperature, menthol produced cold and nociceptive sensations, both of which were suppressed by dynamic contact. When the skin was cooled during static contact, menthol increased nociceptive sensations but not cold sensations; when the skin was cooled during dynamic contact, cold sensations were again unchanged while nociceptive sensations were suppressed. A second experiment tested whether contact suppression of menthol's cold and nociceptive sensations at resting skin temperature was caused by slight deviations of thermode temperature above skin temperature. The results showed that suppression occurred even when the thermode was slightly cooler (-0.5 degrees C) than the skin. These findings support other evidence that the menthol-sensitive channel, TRPM8, plays a role in cold nociception, and raise new questions about how dynamic tactile stimulation may modify perception of nonpainful cold stimulation.     

Slow potentials of the turtle olfactory bulb in response to odor stimulation of the nose.

Odor stimulation of the nose in the box turtle and the gopher tortoise produced a characteristic series of slow potentials in the olfactory bulb which were referred to as the odor evoked response. When recorded with direct coupling, the odor evoked response had 3 components: wave I, a short duration monophasic event; wave II, a long duration variation in the DC potential; and wave III, an oscillatory potential superimposed on wave II. Waves I and II were negative at bulbar surfaces receiving olfactory input and positive deep within the bulb. This series of potentials could be evoked by 3 methods of odor stimulation: (1) large puffs delivered from odorant test bottles, (2) small puffs delivered from a syringe and (3) continuous flow with concentration and nasal flow rate parameters controlled by an olfactometer. When the odor evoked response was recorded at a bulbar locus, these potentials were seen in response to each stimulation and the amplitudes of each wave were reproducible with the same stimulus. The amplitudes of the 3 waves were compared in the gopher tortoise and differed with the 3 odorants tested--high purity geraniol, technical grade geraniol and amyl acetate. Odorant concentration also directly affected the response amplitudes of all 3 wave components. The amplitudes of waves I and III markedly decreased with closely spaced stimulations recovering to near the initial values when the interstimulus interval was increased severalfold. This series of sensory evoked potentials is considered to reflect the processing of odor information from the olfactory receptors by the olfactory bulb.     

PET-based investigation of cerebral activation following intranasal trigeminal stimulation

The present study aimed to investigate cerebral activation following intranasal trigeminal chemosensory stimulation using O15-H2O-PET. A total of 12 healthy male participants underwent a PET scan presented with four scanning conditions; two left-sided intranasal CO(2)-stimuli and two matched baseline conditions consisting of odorless air. CO(2) was used as it produces burning and stinging sensations. Stimulation started 20 s before intravenous injection of the isotope and lasted for the first 60 s of the 5 min scan time. A comparison between CO(2) and baseline showed a pronounced activation of the trigeminal projection area at the base of the postcentral gyrus (primary and secondary somatosensory cortex) which was more intense for the right hemisphere, contralateral to the side of stimulation. In addition, activation was also found in the piriform cortex which is typically activated following odor presentation and thus thought of as primary olfactory cortex. In conclusion, and in line with previously published work, our data suggest that intranasal trigeminal stimulation not only activates somatosensory projection areas, but that it also leads to activation in cerebral areas associated with the processing of olfactory information. This may be interpreted in terms of the intimate relation between the intranasal chemosensory systems.     

Electro-Olfactograms in Humans in Response to Ortho- and Retronasal Chemosensory Stimulation

Aim

Ortho- and retronasal olfaction represent two aspects of a shared sensory system yet evoke different sensations. The differences between ortho- and retronasal olfaction have triggered a number of studies during the past years, which pointed towards a decreased sensitivity to odors presented through the retronasal olfactory pathway. Especially intensity was reported to be lower after retronasal olfactory stimulation. The aim of this study was to investigate how this compares to activation at the level of the olfactory epithelium in humans.

Methods

Trigeminal (CO₂) and olfactory (H₂S, phenylethyl alcohol) stimuli were presented ortho- and retronasally. Electro-olfactograms (EOG) in response to chemosensory stimulation were recorded in 10 participants (6 women, 4 men, mean age 23.4 years).

Results

Typical EOGs were demonstrable after either orthonasal or retronasal stimulation across the stimulus qualities. Overall, EOG amplitudes to retronasal stimulation were smaller when compared to those to orthonasal stimulation, but a significant difference was obtained only in phenylethyl alcohol (p?=?0.048).

Conclusions

The present data indicate that the perceptual differences between ortho- and retronasal olfaction may start at the level of the olfactory epithelium. The data support the idea that the intensity of physically identical stimuli is lower after retronasal stimulation compared to orthonasal stimulus presentation for both olfactory and trigeminal stimuli.

Implications

The current electrophysiological results are in line with reported differences in psychophysical properties of retro- and orthonasal stimulations meaning that different sensations are elicit through these two channels although the same molecule is presented.

     

Threshold and rate sensitivity of low‐threshold thermal nociception

Previous studies have shown that sensations of burning, stinging or pricking can be evoked by warming or cooling the skin to innocuous temperatures [low‐threshold thermal nociception (LTN)] below the thresholds of cold‐ and heat‐sensitive nociceptors. LTN implies that some primary afferent fibers classically defined as warm and cold fibers relay stimulation to the nociceptive system. We addressed this question in humans by determining if different adaptation temperatures (ATs) and rates of temperature change would affect thermal sensation and LTN similarly. In Experiment 1 subjects rated the intensity of warmth, cold and nociceptive sensations produced by increasing steps in temperature (±0.5°C increments) from ATs of 35, 33 and 31°C for cooling, and 30, 32 and 34°C for heating. Depending upon the AT, thresholds for nociceptive and thermal sensations estimated from the rating data differed by as little as ?1.0°C for cooling and +1.5°C for heating. Thresholds of thermal and nociceptive sensations shifted by similar amounts across the three ATs during cooling, whereas during heating the nociceptive threshold was significantly affected only between ATs of 32 and 34°C. In Experiment 2, increasing the rate of temperature change from 0.5 to 4.0°C/s increased the intensity of thermal and nociceptive sensations significantly but the effect was greatest for nociceptive sensations during heating. The results of both experiments are consistent with the mediation of LTN by low‐threshold thermoreceptors, although LTN caused by heating may depend on a subset of fibers that express less sensitive TRP channels than those that serve sensations of warmth at the mildest temperatures.     

Vibrotactile atonal interval correlated with activity in peripheral mechanoreceptive units innervating the human hand

The quality of sensations and the vibrotactile atonal interval-the gap between detection and vibration thresholds-were studied with vibratory stimuli of varying frequency (20, 80 and 160 Hz) and duration (100, 400 and 800 ms) applied to the hairy and glabrous skin of the hand. Detection and vibration thresholds were also determined while simultaneously recording single unit activity from the radial nerve innervating the hairy skin of the hand. Both thresholds were lower on the glabrous than the hairy skin, and the thresholds decreased on both skin areas with increasing vibration frequency. A sensation of short duration was elicited at detection threshold only with a 20-Hz stimulus of 100-ms duration; with other frequency-duration combinations sensations of longer duration were reported. Considerably larger vibration amplitudes were needed on both skin areas for the sensations to be unequivocal with respect to duration and pitch (vibration threshold). There was no significant effect of stimulus duration on vibrotactile thresholds. The width of the average atonal intervals was above 10 dB on both skin areas, and with increasing vibration frequency, decreasing values of atonal intervals were obtained on the hairy skin, whereas considerably increasing values were obtained on the glabrous skin. Recording of single unit activity indicates that on the hairy skin detection of the stimulus at 20 Hz is correlated with activation of slowly adapting (SA) type II and the most sensitive rapidly adapting (RA) units, while distinct vibratory sensations involve entrainment of RA units. Also at 80 Hz, non-pacinian units could contribute to the mechanism of vibrotactile thresholds, whereas at 160 Hz only pacinian (PC) units are involved.     

Evidence of conscious and subconscious olfactory information processing during word encoding: a magnetoencephalographic (MEG) study

The present study was meant to distinguish between unconscious and conscious olfactory information processing and to investigate the influence of olfaction on word information processing. Magnetic field changes were recorded in healthy young participants during deep encoding of visually presented words whereby some of the words were randomly associated with an odor. All recorded data were then split into two groups. One group consisted of participants who did not consciously perceive the odor during the whole experiment whereas the other group did report continuous conscious odor perception. The magnetic field changes related to the condition 'words without odor' were subtracted from the magnetic field changes related to the condition 'words with odor' for both groups. First, an odor-induced effect occurred between about 200 and 500 ms after stimulus onset which was similar in both groups. It is interpreted to reflect an activity reduction during word encoding related to the additional olfactory stimulation. Second, a later effect occurred between about 600 and 900 ms after stimulus onset which differed between the two groups. This effect was due to higher brain activity related to the additional olfactory stimulation. It was more pronounced in the group consisting of participants who consciously perceived the odor during the whole experiment as compared to the other group. These results are interpreted as evidence that the later effect is related to conscious odor perception whereas the earlier effect reflects unconscious olfactory information processing. Furthermore, our study provides evidence that only the conscious perception of an odor which is simultaneously presented to the visual presentation of a word reduces its chance to be subsequently recognized.     

Evidence that tactile stimulation inhibits nociceptive sensations produced by innocuous contact cooling

It was recently shown that stinging, pricking or burning is reliably perceived by some individuals when the skin is cooled to temperatures as mild as 25-30 degrees C. These seemingly paradoxical sensations, which have been termed innocuous-cold nociception (ICN), were significant only when cooling was produced by a thermode resting statically on the skin (static contact); touching an already cooled thermode to the skin (dynamic contact) produced reports of only coolness and cold. The present study investigated the hypothesis that ICN is inhibited by tactile stimulation produced when a thermode contacts the skin. Experiment 1 pitted the tactile hypothesis against an alternative explanation that inhibition results from higher rates of skin cooling during dynamic contact. ICN was measured at three different cooling rates (-1.0, -2.5, -5.0 degrees C/s) when the thermode was resting on the skin or was touched to the skin at the moment cooling began. The results supported the tactile hypothesis: faster cooling rates during static contact led to stronger rather than weaker nociceptive sensations, and ICN was suppressed even when dynamic contact was coincident with the onset of cooling, and thus could not affect cooling rate. Experiment 2 confirmed the latter result and showed that suppression was greatest at 28 degrees C, less at 24 degrees C, and not significant at 18 degrees C. We conclude that dynamic tactile stimulation produced by contact with a surface inhibits the nociceptive component of innocuous but not noxious cooling. The implications of this conclusion for the role of cold perception in behavioral thermoregulation versus haptic perception, and for theories of cold perception in general, are discussed.     

Cardiorespiratory variables and sensation during stimulation of the left vagus in patients with epilepsy

We studied physiological and sensory effects of left cervical vagal stimulation in six adult patients receiving this stimulation as adjunctive therapy for intractable epilepsy. Stimulus strength varied among subjects from 0.1 to 2.1 microCoulomb (microC) per pulse, delivered in trains of 30-45 s at frequencies from 20 to 30 Hz; these stimulation parameters were standard in a North American study. The stimulation produced no systematic changes in ECG, arterial pressure, breathing frequency tidal volume or end-expiratory volume. Five subjects experienced hoarseness during stimulation. Three subjects with high stimulus strength (0.9-2.1 microC) recalled shortness of breath during stimulation when exercising; these sensations were seldom present during stimulation at rest. No subjects reported the thoracic burning sensation or cough previously reported with chemical stimulation of pulmonary C fibers. Four of six subjects (all those receiving stimuli at or above 0.6 microC) experienced a substantial reduction in monthly seizure occurrence at the settings used in our studies. Although animal models of epilepsy suggest that C fibers are the most important fibers mediating the anti-seizure effect of vagal stimulation, our present findings suggest that the therapeutic stimulus activated A fibers (evidenced by laryngeal effects) but was not strong enough to activate B or C fibers.     

A novel tDCS sham approach based on model-driven controlled shunting

BackgroundTranscranial direct current stimulation (tDCS), a non-invasive brain stimulation technique able to transiently modulate brain activity, is surging as one of the most promising therapeutic solutions in many neurological and psychiatric disorders. However, profound limitations exist in current placebo (sham) protocols that limit single- and double-blinding, especially in non-naïve subjects.ObjectiveTo ensure better blinding and strengthen reliability of tDCS studies and trials, we tested a new optimization algorithm aimed at creating an “active” sham tDCS condition (ActiSham hereafter) capable of inducing the same scalp sensations perceived during real stimulation while preventing currents from reaching the cortex and cause changes in brain excitability.MethodsA novel model-based multielectrode technique — optimizing the location and currents of a set of small electrodes placed on the scalp — was used to control the relative amount of current delivered transcranially in real and placebo multichannel tDCS conditions. The presence, intensity and localization of scalp sensations during tDCS was evaluated by means of a specifically designed questionnaire administered to the participants. We compared blinding ratings by directly addressing subjects’ ability to discriminate across conditions for both traditional (Bifocal-tDCS and Sham, using sponge electrodes) and our novel multifocal approach (both real Multifocal-tDCS and ActiSham). Changes in corticospinal excitability were monitored based on Motor Evoked Potentials (MEPs) recorded via concurrent Transcranial Magnetic Stimulation (TMS) and electromyography (EMG).ResultsParticipants perceived Multifocal-tDCS and ActiSham similarly in terms of both localization and intensity of scalp sensations, whereas traditional Bifocal stimulation was rated as more painful and annoying compared to its Sham counterpart. Additionally, differences in scalp localization were reported for active/sham Bifocal-tDCS, with Sham tDCS inducing more widespread itching and burning sensations. As for MEPs amplitude, a main effect of stimulation was found when comparing Bifocal-Sham and ActiSham (F_(1,13) = 6.67, p = .023), with higher MEPs amplitudes after the application of Bifocal-Sham.ConclusionsCompared to traditional Bifocal-tDCS, ActiSham offers better participants’ blinding by inducing very similar scalp sensations to those of real Multifocal tDCS both in terms of intensity and localization, while not affecting corticospinal excitability.     

Evaluation of methods for eliciting somatosensory-evoked potentials in the awake,freely moving rat

To standardise the method of eliciting somatosensory-evoked potentials (SEPs), SEPs were generated by electrical stimulation of different stimulus sites and recorded bilaterally from the primary somatosensory cortex (S1) and from midline in awake, freely moving rats. Increasing stimulus intensity enhanced amplitudes of all SEPs. At supramaximal stimulation, SEPs following vibrissae and tail stimulation (V-SEP and Ta-SEP, respectively) but not following trunk stimulation (Tr-SEP), fulfilled our criterion of signal-to-noise ratio >or=4. The first V-SEP component coincided with a stimulus artefact, disqualifying these recordings for a standard stimulation protocol. The Ta-SEP generated stable and reproducible recordings and was considered to be the preferred technique. Early components of the contralateral S1 recorded V-SEP and Tr-SEP occurred at latencies different from the other recordings. Increasing stimulus repetition rate (SRR) decreased amplitudes of all SEPs. At the highest obtainable SRR, the amplitude between the V-SEP second positive and second negative components in all recordings was 70-80% of the amplitude at 0.1 Hz, whereas peak amplitudes of subsequent components and those of the Tr-SEP and Ta-SEP were 20-50%. These results indicate that the different SEP components might be generated by different ascending neural pathways.     

Suppression of C-fibre discharges upon repeated heat stimulation may explain characteristics of concomitant pain sensations

Nociceptors with unmyelinated axons were recorded from the superficial radial nerves of 7 volunteers. A sequence of uniform radiant heat stimuli of 18 s duration, starting from an individually adjusted adapting temperature were used to raise the skin surface temperature by 6°C to a painful level (41–43 °C). These stimuli followed each other at 3 different interstimulus intervals of 35 s, 70 s and 105 s, occurring in a random order. The subjects were asked to track the time course of the stimulus-evoked sensation by manipulating the length of a light bar. Adaptation and stimulus temperatures were chosen to induce sensations of heat and/or pain. All nociceptors studied responded to these stimuli with a phasic response of 3–5 s duration, often followed by a low frequency tonic discharge, lasting as long as the stimulus. No discharges were seen in interstimulus periods. Discharge rates during the phasic responses were linearly related to interval duration, whereas tonic discharges were not influenced by the preceding interval. In parallel readings of pain responses were lower up to the 10th second of the stimulus after short rather than after long intervals. These results indicate that the suppression of C-fibre nociceptor discharges during repetitive stimulation may explain concomitant reductions in the magnitude of human pain sensations.     

Leg paresthesias induced by magnetic brain stimulation in patients with thoracic spinal cord injury

We studied the induction of leg paresthesias by magnetic stimulation of the brain in seven patients with thoracic T9-12 spinal cord injury and in four normal volunteers by delivering transcranial magnetic stimulation over scalp positions 1 cm apart with a Cadwell MES-10 magnetic stimulator and an 8-shaped magnetic coil at 100% stimulus intensity. We asked subjects to report sensations felt after each stimulus. In all normal subjects, magnetic stimulation evoked sensations described as tingling or a wave descending along the leg, usually accompanied by EMG responses in leg muscles. In three of the seven patients, stimulation evoked sensations of tingling, numbness, touch, or a wave descending along the leg, lasting up to 10 seconds and referred to different parts of the legs and toes. In the patients, sensations were felt more distally the closer the site of stimulation was to the midline. Patients with leg paresthesias had less motor reorganization in abdominal muscles than those without paresthesias. These findings suggest that portions of the cortical representation areas for body parts deafferented by a complete spinal cord injury can remain related to those body parts for up to several years. A central origin of these paresthesias is probable.     

Pupillary responses to intranasal trigeminal and olfactory stimulation

The aim of the present study was to investigate whether pupillary responses to odorous stimuli reflect their intensity or hedonic tone. A total of 21 healthy subjects participated in the study. Using a computer-controlled olfactometer, subjects received intranasal stimuli including odors of rose (PEA; 2 concentrations), lemon and rotten eggs, plus the trigeminal irritant CO₂ (also at two concentrations). Changes in the pupil diameter were obtained ipsilaterally to the side of stimulus presentation. Both trigeminal and olfactory stimulation produced an increase in pupillary diameter. Latencies for pupillary reaction were fastest for the higher concentration of CO₂ and slowest after the presentation of PEA at the low concentration. Response amplitudes were largest in response to stimulation with CO₂ at the high concentration, while they were smallest in response to odorous stimulation with PEA. Response latencies decreased with increasing stimulus intensity. No such correlation was found for hedonic ratings and pupillary reactions. Thus, the change in the pupillary diameter indicates differences between stimulus modalities and stimulus strength, but not pleasantness or unpleasantness of the odors.     

Further Studies of Effects of Chlorpromazine on the Contingent Negative Variation

The effect of 25 mg of chlorpromazine (CPZ) on the contingent negative variation (CNV) at Cz and Oz was studied in nine male subjects. Two kinds of warning stimulus (S1)—imperative stimulus—and motor response (MR) were used. A click as S1 was common to both, while either flashes or electrical stimulation was used as S2. Simultaneously with CNV recording, the reaction time of the finger movement as MR to S2 was measured in five of nine subjects. The results obtained were as follows. 1) CNV amplitudes after CPZ administration were decreased significantly both at Cz and Oz when S2 was flashes and only at Cz when S2 was electrical stimulation. 2) Significant positive correlations of CNV amplitudes between Cz and Oz were found both before and after the drug administration. 3) Reaction times to flashes and electrical stimulation as S2 were not affected by CPZ administration. 4) The reaction time to flashes was significantly shorter than that to electrical stimulation irrespective of pre- and post-administration of CPZ.     

High-resolution functional labeling of vertebrate and invertebrate olfactory receptor neurons using agmatine, a channel-permeant cation

Methods are described for odor-stimulated labeling of olfactory receptor neurons (ORNs) of the freshwater zebrafish Danio rerio and the marine spiny lobster Panulirus argus. Permeation of a cationic molecule, 1-amino-4-guanidobutane (=agmatine, AGB), through ion channels following odor stimulation, and its detection by an anti-AGB antibody, allow labeling of odor-stimulated ORNs. Parameters adjusted to optimize activity-dependent labeling included labeling medium ionic composition, stimulation times, and AGB concentration. For lobsters, 7% of ORNs were labeled by a complex odor, oyster mixture, under optimal conditions, which was stimulation for 5 s per min for 60 min with 20 mM AGB in artificial seawater with reduced sodium and calcium concentrations. AGB was a weak odorant for lobsters; it elicited only a small electrophysiological response from ORNs and labeled<1% of the ORNs during stimulation with AGB in the absence of odors. For the zebrafish, stimulation for 10 s per min for 10 min with 5 mM AGB plus odorant ( -glutamine) in fish Ringer’s solution was the optimal labeling condition, resulting in labeling of 17% of the olfactory epithelial area. Approximately 6% of the olfactory epithelium was labeled during stimulation with a control stimulus, AGB alone. This labeling by AGB alone suggests it is an olfactory stimulus for zebrafish; a conclusion supported by electrophysiological recordings. We used electrophysiological assays and channel blockers to examine, for each species, potential ion channels for entry of AGB into ORNs. These results show that AGB can be used as an activity-dependent label for chemoreceptor neurons of diverse phyla living in a range of environmental conditions.     

Steady-state vibration somatosensory evoked potentials: physiological characteristics and tuning function.

OBJECTIVE: The steady-state somatosensory evoked potentials (S-SEPs) to vibratory stimulation were recorded to characterize their physiological properties. METHODS: Vibratory stimuli were applied to the right palmar surface in 10 normal subjects. A total of 200 responses were recorded from electrodes at 2 cm posterior to C3, Cz and C4 and 2 cm anterior to C3. All responses were Fourier analyzed and the amplitudes of the first (1F) and second (2F) harmonic components were thus obtained. The effects of modulation frequency (5-30 Hz) and stimulus intensity (0.001-0.1 Newton (N)) on S-SEPs were studied. RESULTS: The amplitudes of 1F and 2F were greatest at the electrode 2 cm posterior to C3, 1F being predominant. The mean 1F amplitudes as a function of modulation frequency showed a bimodal distribution with a trough at 14 Hz and a peak at 21 Hz. The mean 1F amplitudes showed a linear increase of up to 0.05 N and thereafter reached a plateau against the logarithmic stimulus intensity axis. CONCLUSION: Vibratory S-SEPs may originate from the primary somatosensory cortex and provide information on the fast-adapting mechanoreceptive afferents. The temporal resonance at 21 Hz places the somatosensory system between the visual and auditory systems.     

Neurobehavioral responses of neonatal rats to previously experienced odors of different concentrations.

Neonatal rats acquire an olfactory preference following daily exposure to an odor that is accompanied by tactile stimulation. In the present study, we determined the neurobehavioral responses of pups trained and tested with odors of either the same or different concentration. On postnatal day (PND) 1-18, all animals were exposed for 10 min/day to either peppermint or air while receiving perineal tactile stimulation. On PND 19, pups trained with a low odor concentration preferred that odor to air, regardless of its concentration and showed equal preference between odor concentrations. These results suggest both that pups can learn to prefer a specific odor concentration and that they can learn to recognize odor quality across concentrations. To determine the neural responses to such stimuli, trained and control pups were exposed to either low or high peppermint odor concentrations following an injection of 14C-labelled 2-deoxyglucose (2-DG). Early experience with the high odor concentration resulted in the 2-DG uptake response to both test odor concentrations which was higher than that of pups that had previous experience with either the low odor concentration or with clean air. Though the 2-DG density did not increase with test odor concentration, the size of the 2-DG foci did, regardless of previous experience. The 2-DG response to odor concentration is, therefore, influenced by both previous experience and immediate odor stimulus characteristics that are revealed in parallel responses within the olfactory bulb.