Interaction between age and perceptual similarity in olfactory discrimination learning in F344 rats: relationships with spatial learning.

Emerging evidence suggests that aging is associated with a reduced ability to distinguish perceptually similar stimuli in one's environment. As the ability to accurately perceive and encode sensory information is foundational for explicit memory, understanding the neurobiological underpinnings of discrimination impairments that emerge with advancing age could help elucidate the mechanisms of mnemonic decline. To this end, there is a need for preclinical approaches that robustly and reliably model age-associated perceptual discrimination deficits. Taking advantage of rodents' exceptional olfactory abilities, the present study applied rigorous psychophysical techniques to the evaluation of discrimination learning in young and aged F344 rats. Aging did not influence odor detection thresholds or the ability to discriminate between perceptually distinct odorants. In contrast, aged rats were disproportionately impaired relative to young on problems that required discriminations between perceptually similar olfactory stimuli. Importantly, these disproportionate impairments in discrimination learning did not simply reflect a global learning impairment in aged rats, as they performed other types of difficult discriminations on par with young rats. Among aged rats, discrimination deficits were strongly associated with spatial learning deficits. These findings reveal a new, sensitive behavioral approach for elucidating the neural mechanisms of cognitive decline associated with normal aging.

Characterizing olfactory binary mixture interactions in Fischer 344 rats using behavioral reaction times.

Response times provide essential subthreshold perceptual data that extend beyond accuracy alone. Behavioral reaction times (RTs) were used to characterize rats' ability to detect individual odorants in a series of complimentary binary odorant mixture ratios. We employed an automated, liquid-dilution olfactometer to train Fischer 344 rats (N = 8) on an odor identification task using nonreinforced probe trials. Binary mixture ratios composed of aliphatic odorants (citral and octanol) were arranged such that relative contributions of the 2 components varied systematically by a factor of 1% (v/v). Odorant concentrations for the target (S+), control (S-), and mixture (S+:S-) odorants were presented relative to threshold for each rat. Rats were initially trained to respond by licking at a spout to obtain liquid reward for either citral or octanol as the reinforced target (S+) odorant. After achieving 100% accuracy, rats were transferred to variable ratio (VR 2) reinforcement for correct responding. Nonreinforced probe trials (2 per block of 22 trials) were tested for each mixture ratio and recorded as either S+ (rats lick-responded in the presence of the mixture) or S- (rats refrained from licking), thereby indicating detection of the trained, S+ odorant. To determine the perceived salience for each ratio, RTs (latency from odorant onset to lick response) were recorded for each trial. Consistent with previous studies, RTs for both odorants were shortest (~150-200ms) when the probe trials consisted of a single, monomolecular component. Binary mixtures that contained as little as 1% of the S-, nontarget odorant, however, were sufficiently different perceptually to increase behavioral RTs (i.e., rats hesitated longer before responding); RTs changed systematically as a function of the binary ratio. Interestingly, the rate of RT change was dependent on which odorant served as the S+, suggesting an asymmetric interaction between the 2 odorants. The data demonstrate the value of behavioral RT as a sensitive measure of suprathreshold perceptual responding.

A technique for characterizing the time course of odor adaptation in mice.

Although numerous studies have analyzed the temporal characteristics underlying olfactory adaptation at the level of the olfactory receptor neuron, to date, there have been no comparable behavioral measures in an animal model. In this study, odor adaptation was estimated in a group of mice employing a psychophysical technique recently developed for use in humans. The premise of this technique is that extended presentation of an odorant will produce odor adaptation, decreasing the sensitivity of the receptors and increasing thresholds for a brief, simultaneous target odorant presented at different time points on the adaptation contour; adaptation is estimated as the increase in threshold for a target odorant presented simultaneously with an adapting odorant, across varying adapting-to-target odorant onset delays. Previous research from our laboratory suggests that this method provides a reliable estimate of the onset time course of rapid adaptation in human subjects. Consistent with physiological and behavioral data from human subjects, the present findings demonstrate that measurable olfactory adaptive effects can be observed for odorant exposures as brief as 50-100ms, with asymptotic levels evident 400-600ms following adapting odorant onset. When compared with the adaptation contour in humans using the same odorant and stimulus paradigm, some differences in the onset characteristics are evident and may be related to sniffing behavior and to relative differences in thresholds. These data show that this psychophysical paradigm can be adapted for use in animal models, where experimental and genetic manipulations can be used to characterize the different mechanisms underlying odor adaptation.

Characterizing olfactory perceptual similarity using carbon chain discrimination in Fischer 344 rats.

Performance on olfactory tests can be influenced by a number of stimulus characteristics including chemical structure, concentration, perceptual similarity, and previous experience with the test odorants. Few of these parameters have been extensively characterized in the Fischer 344 rat strain. To investigate how odor quality affects perception in this rat strain, we measured how graded perceptual similarity, created by varying carbon chain length across a series of homologous alcohol pairs, influenced odor discrimination using a liquid-motivated go/no-go task. We employed an automated, liquid-dilution olfactometer to train Fischer 344 rats (N = 8) on a 2-odor discrimination task. Six odorants (1-propanol, 1-butanol, 1-pentanol, 1-hexanol, 1-heptanol, and 1-octanol) were arranged to produce 15 novel odorant pairs differing between 1 and 5 carbon atoms; testing sessions included presentation of only 1 pseudorandomly assigned pair daily (200 trials). Results show that although rats can learn to discriminate between any 2 odorant pairs, performance declines systematically as the pairs become more structurally similar and, therefore, more perceptually confusing. As such, the easier discrimination pairs produced reliable ceiling effects across all rats, whereas performance for the difficult discrimination pairs was consistently worse, even after repeated testing. These data emphasize the importance of considering odorant stimulus dimensions in experimental designs employing olfactory stimuli. Moreover, establishing baseline olfactory performance in Fischer 344 rats may be particularly useful for predicting age-related cognitive decline in this model.

Evidence of rapid recovery from perceptual odor adaptation using a new stimulus paradigm.

By attenuating neural and perceptual responses to sustained stimulation, adaptation enhances the detection of new, transient stimuli. Disadaptation serves a similarly important role as a temporal filter for chemoreceptor cells, producing rapid recovery of sensitivity upon termination of the adapting odorant. Previous research from our laboratory indicated that a rapid form of odor adaptation can be measured using a novel, simultaneous-odorant paradigm. In the present study, we extended the earlier method by measuring recovery from adaptation. Perceptual odor adaptation was measured by estimating psychophysical detection thresholds in a group of college-aged student volunteers (N = 20; 12 females, eight males) for a self-adapting odorant, vanilla extract. To induce adaptation, the time between the onset of the adapting odorant and the onset of the target odorant was systematically varied. By first quantifying adaptation, recovery of sensitivity could therefore be investigated by using different time points following the termination of the adapting odorant. Consistent with our previous work, thresholds estimated in the presence of the simultaneous adapting odorant were significantly increased, reflecting a decrease in sensitivity due to adaptation. Conversely, approximately 100 ms following termination of the adapting stimulus (the briefest delay tested), sensitivity began to rapidly recover. Nevertheless, some residual adaptation was evident at the longest offset delay of 500 ms. These findings suggest that the recovery from adaptation proceeds at least as rapidly as the onset of adaptation, a finding that is consistent with physiological evidence from olfactory receptors. These data also suggest the effectiveness of this new odorant paradigm in characterizing the temporal characteristics underlying these critical olfactory mechanisms.