A. Holley

Receptor cell responses to odorants: Similarities and differences among odorants

An extensive exploration of the discriminating properties of olfactory receptors cells has been conducted in our laboratory through the statistical processing of single cell responses recorded in the frogs olfactory epithelium. Similarities between odorant stimulating properties could be demonstrated by comparing the complex response profiles of receptor cells, resulting in the concept of odorant groups which depicts consistent relationships found between some odorous compounds. The recording technique limits the number of odorants which can be tested and compared within the same series of experiments. Thus, based upon previous studies we have chosen a specific set of 20 odorants whose characteristics are known but, up to this time, have not been compared in the same experimental system. These odorants were: acetophenone, anisole, n-butanol, DL-camphor, cyclodecanone, 1,8-cineole, p-cymene, D-citronellol, n-heptanol, isoamyl acetate, isovaleric acid, D-limonene, methyl amylketone, L-menthol, phenol, thiophenol, pyridine, thymol, cyclohexanol, cyclohexanone. The pattern of similarities between these odorants, as delineated with the aid of correlation coefficient computation, factor analysis and non-hierarchical taxonomy, confirms the reality of several odorant groups previously suggested and describes their cross-relationships. The receptor mechanisms underlying these odorant groups are discussed. Because reliable prominent features of the olfactory stimulus space can be established on an objective basis, the findings are proposed as a reference for future studies on other aspects of olfactory discrimination.

Spatial distribution of [14C]2-deoxyglucose uptake in the olfactory bulbs of rats stimulated with two different odours

The uptake of [14C]2-deoxy-D-glucose (2-DG) has been studied by autoradiography in the olfactory bulbs of control and odour-stimulated rats. The sites of highest 2-DG-uptake coincide very accurately with individual glomeruli. The other bulbar histological layers appear to be far less metabolically affected by the olfactory stimulation. The mapping of the glomerular activation has been compared in two groups of animals stimulated with two different odours. The patterns of selective glomerular 2-DG-uptake are rather similar within each group. They differ from one group to the other by the number and localization of the highly labelled glomeruli. It can be inferred from our observations that a few glomeruli are metabolically highly activated by a strong and pure odour stimulation. A correlation between the quality of the odour and the pattern of glomerular activation may be supposed but has to be confirmed with other compounds.

Functional Neuroanatomy of Different Olfactory Judgments

Humans routinely make judgments about olfactory stimuli. However, few studies have examined the functional neuroanatomy underlying the cognitive operations involved in such judgments. In order to delineate this functional anatomy, we asked 12 normal subjects to perform different judgments about olfactory stimuli while regional cerebral blood flow (rCBF) was measured with PET. In separate conditions, subjects made judgments about the presence (odor detection), intensity, hedonicity, familiarity, or edibility of different odorants. An auditory task served as a control condition. All five olfactory tasks induced rCBF increases in the right orbitofrontal cortex (OFC), but right OFC activity was highest during familiarity judgments and lowest during the detection task. Left OFC activity increased significantly during hedonic and familiarity judgments, but not during other odor judgments. Left OFC activity was significantly higher during hedonicity judgments than during familiarity or other olfactory judgments. These data demonstrate that aspects of odor processing in the OFC are lateralized depending on the type of olfactory task. They support a model of parallel processing in the left and right OFC in which the relative level of activation depends on whether the judgment involves odor recognition or emotion. Primary visual areas also demonstrated a differential involvement in olfactory processing depending on the type of olfactory task: significant rCBF increases were observed in hedonic and edibility judgments, whereas no significant rCBF increases were found in the other three judgments. These data indicate that judgments of hedonicity and edibility engage circuits involved in visual processing, but detection, intensity, and familiarity judgments do not.

Olfactory receptor cell function is affected by trigeminal nerve activity

In the frog, antidromic electrical stimulation of the ophthalmic branch of the trigeminal nerve (NV-ob) evokes a slow potential in the olfactory mucosa, modifies the activity of receptor cells and modulates the responses to odour. Substance P (SP) application evokes similar electrical responses. These results imply that the functioning of the olfactory system might be controlled at the receptor cell level. It is suggested that the trigeminal system could modulate the activity of the olfactory receptor cells via a local axon reflex which may result in the release of SP.

The activity of olfactory receptor cells is affected by acetylcholine and substance P.

The effects of acetylcholine (ACh) and substance P (SP) on the unit activity of receptor cells recorded from the superfused frog olfactory mucosa were studied. Single neurones were excited or, more rarely, depressed by the application of chemicals. Cholinergic antagonists were used to investigate the involvement of nicotinic and muscarinic receptors in the recorded responses. The ACh-evoked firing was antagonized by D-tubocurarine (D-TC), atropine (ATR) and SP. Responses to SP appeared to be D-TC resistant, but activation by the peptide was moderately antagonized by ATR. The results suggest that ACh and SP could affect the functioning of the olfactory receptor cells.

Involvement of the olfactory bulb in consolidation processes associated with long-term memory in rats.

In a daily training paradigm, rats were trained to discriminate between spatially distinct electrical stimulations delivered to one olfactory bulb. Xylocaine injections were used to disrupt the olfactory bulb functioning in the region close to the electrode tips for 1 hr after training session. The treatment started either just after the session or 2 hr later. When compared with the performance of saline-injected rats, the performance of Xylocaine-injected rats was unimpaired except when the treatment started just after the daily session. In that case, acquisition of the task was slightly altered, and retention over a 5-day period was dramatically impaired. We therefore concluded that, within about 1 hr following training, the olfactory bulb is engaged in consolidation processes critical for long-term retention of learned olfactory cues.

Evidence for the Involvement of Rat Olfactory Bulb in Processes Supporting Long‐Term Olfactory Memory

Current advances in the neurobiology of learning and memory suggest the existence of experience‐induced plasticity in sensorial pathways conveying relevant information to higher integrative brain structures. For instance, olfactory learning is known to induce long‐lasting modifications of neural activity at the level of the first relay structure of the olfactory system, the olfactory bulb. The observed forms of plasticity depend on the action exerted during learning by ascending neuromodulatory systems, such as the noradrenergic (NA) system originating from the locus ceruleus. This study was aimed at investigating the importance of olfactory bulb plasticity in learning and retention of an olfactory task. In a daily training schedule animals had to learn to use multi‐site electrical stimulation patterns of the olfactory bulb as discriminative cues for choosing between a palatable and a nonpalatable solution. We first examined the effects of a continuous intrabulbar infusion of propranolol (a β‐NA receptor antagonist) carried out during the learning period. We found that this treatment neither impaired the retention of a previously learned task nor the learning of a new task. However, the animals presented a severe deficit in long‐term retention (>5 days) of the task learned under perfusion. Unexpectedly, this effect cannot be ascribed to a selective blockade of β‐NA receptors since infusion of the drug vehicle (saline‐ascorbate) produced exactly the same deficit while a saline solution remained without effect. A final experiment showed that the selective deficit in long‐term retention was not observed when the infusion of the saline‐ascorbate solution started on the day following completion of learning. Taken together, these results suggest that ascorbate‐sensitive neural processes occurring within the olfactory bulb during learning are of functional importance for long‐term storage of olfactory information.

Does the Trigeminal Nerve Control the Activity of the Olfactory Receptor Cells?a

In a previous study, we have investigated the effects of acetylcholine and substance P (SP) on the electrical activity of the frog olfactory mucosa. Stimulation by these chemicals elicited low-threshold slow electrical potentials’ and modified the spontaneous activity of olfactory receptor cells2 (FIG. 1). These findings suggest that, in physiological conditions, acetylcholine and SP might be released from nerve terminals in the olfactory mucosa. As an argument for this hypothesis, nerve fibers displaying SP-like immunoreactivity were detected in the lamina propria and within the epithelium of the frog olfactory mucosa (unpublished observation). These fibers might be of trigeminal origin since the trigeminal nerve, which innervates the olfactory mucosa, contains SP-like immunoreactive neurons.’ In the frog, trigeminal neurons send fibers to the olfactory mucosa via the ophthalmic branch of the trigeminal nerve (NV-ob). We have investigated the effects induced by the antidromic electrical stimulation of NV-ob on the electrical activity of the frog olfactory mucosa. The stimulation of the peripheral stump of NV-ob was performed with 10-msec pulses at 30 V, 20 Hz. Electrical volleys of oneto two-second duration delivered to NV-ob evoked slow electrical potentials in the olfactory mucosa, with the surface negative in relation to the indifferent electrode (FIG. 2). There was a delay of one to two seconds from the onset of the stimulation to the start of the response. In most preparations, the negative potential was a single wave that lasted for two to 15 seconds (FIG. 2A); the average amplitude was about 1 mV. In a few preparations, this wave was followed by a second wave that lasted for one to three minutes with a peak amplitude of 2-4 mV (FIG. 2B). During the single-wave potentials, the spontaneous firing rate of olfactory receptor cells was increased (FIG. 2A) or, more rarely, unchanged. During the last phases of the compound potentials, the firing rate of receptor cells was decreased (FIG. 2B); also, the peak amplitude of the electroolfactogram evoked by isoamylacetate was reduced; the unit responses to this odorant were reduced or suppressed. Since capsaicin is known to deplete SP from primary sensory neurons, we examined its effects on antidromically generated potentials. A 10-minute exposure of the olfactory mucosa to capsaicin vapors suppressed these potentials. Moreover, SP (lO-’M) modified the responsiveness of the superfused mucosa to isoamylacetate. These findings

Investigations of Receptive Fields of Olfactory Bulb Neurons in the Frog

In curarized frogs, an array of nine micropipettes (diam. 100 pm) filled with saline was placed on the ventral aspect of the OE (FIG. lA), covering 2.5-4 mm’. These electrodes were connected to an electrical generator operating under constant current or constant voltage. It delivered long-lasting pulses of positive polarity with a rising slope, a plateau, and a progressive termination (FIG. 1B). The stimulation induced phasic-tonic discharges from receptor cells located close to the electrodes‘ (FIG. 1B). Extracellular unitary responses of OB neurons evoked by focal increase in receptor cell activity were recorded from six regions of the ipsilateral OB.

A Specific Type of Cognition

Olfactory experience is difficult to define: From ineffable to unmentionable, it seems to remain in the limbo of cognition. More than any artists work, the competence of the perfumer is a challenge for explication. The few artists who are able to communicate in writing about their creative processes are mainly plasticians (painters and sculptors), musicians, and, of course, writers. As regards chemical senses, the writings are extremely rare, and the very status of “artist” is not easily conferred. As an example, Edmond Roudnitska faced a difficult task in his effort to have olfaction accepted into the realm of aesthetics. In Chapter 1, Annick Le Guerer proposes an explanation for that misappreciation that has to do with the history of Western philosophy: Our philosophical heritage denies any nobility to olfaction and taste, as compared with the other senses, and depreciates them almost systematically. Psychoanalysis has cited that fact as evidence that civilization can be built only if there is repression of smell. However, as Le Guerer points out, the history of psychoanalysis itself is marked by fantastic representations of the nose and its functions within the relationship linking Freud and Fliess – their unconscious montre son nez in the learned conception of smell. Moving away from the neurophysiology of smell, Andre Holley, in Chapter 2, looks into the perfumers knowledge, which remains largely secret and intuitive. What is the difference between expert and novice, artist and amateur in the cognitive treatment of odors?