Faculty Bibliography

Historical and psychophysical literature has demonstrated a perceptual interplay between olfactory and auditory stimuli-the neural mechanisms of which are not understood. Here, we report novel findings revealing that the early olfactory code is subjected to auditory cross-modal influences. In vivo extracellular recordings from the olfactory tubercle, a trilaminar structure within the basal forebrain, of anesthetized mice revealed that olfactory tubercle single units selectively respond to odors-with 65% of units showing significant odor-evoked activity. Remarkably, 19% of olfactory tubercle single units also showed robust responses to an auditory tone. Furthermore, 29% of single units tested displayed supraadditive or suppressive responses to the simultaneous presentation of odor and tone, suggesting cross-modal modulation. In contrast, olfactory bulb units did not show significant responses to tone presentation nor modulation of odor-evoked activity by tone-suggesting a lack of olfactory-auditory convergence upstream from the olfactory tubercle. Thus, the tubercle presents itself as a source for direct multimodal convergence within an early stage of odor processing and may serve as a seat for psychophysical interactions between smells and sounds

Memory and its underlying neural plasticity play important roles in sensory discrimination and cortical pattern recognition in olfaction. Given the reported function of slow-wave sleep states in neocortical and hippocampal memory consolidation, we hypothesized that activity during slow-wave states within the piriform cortex may be shaped by recent olfactory experience. Rats were anesthetized with urethane and allowed to spontaneously shift between slow-wave and fast-wave states as recorded in local field potentials within the anterior piriform cortex. Single-unit activity of piriform cortical layer II/III neurons was recorded simultaneously. The results suggest that piriform cortical activity during slow-wave states is shaped by recent (several minutes) odor experience. The temporal structure of single-unit activity during slow waves was modified if the animal had been stimulated with an odor within the receptive field of that cell. If no odor had been delivered, the activity of the cell during slow-wave activity was stable across the two periods. The results demonstrate that piriform cortical activity during slow-wave state is shaped by recent odor experience, which could contribute to odor memory consolidation

Alzheimer's disease often results in impaired olfactory perceptual acuity-a potential biomarker of the disorder. However, the usefulness of olfactory screens to serve as informative indicators of Alzheimer's is precluded by a lack of knowledge regarding why the disease impacts olfaction. We addressed this question by assaying olfactory perception and amyloid-beta (Abeta) deposition throughout the olfactory system in mice that overexpress a mutated form of the human amyloid-beta precursor protein. Such mice displayed progressive olfactory deficits that mimic those observed clinically-some evident at 3 months of age. Also, at 3 months of age, we observed nonfibrillar Abeta deposition within the olfactory bulb-earlier than deposition within any other brain region. There was also a correlation between olfactory deficits and the spatial-temporal pattern of Abeta deposition. Therefore, nonfibrillar, versus fibrillar, Abeta-related mechanisms likely contribute to early olfactory perceptual loss in Alzheimer's disease. Furthermore, these results present the odor cross-habituation test as a powerful behavioral assay, which reflects Abeta deposition and thus may serve to monitor the efficacy of therapies aimed at reducing Abeta

The olfactory code is influenced by numerous factors, including behavioral state, odor-sampling patterns and cross-modal sensory convergence. Growing evidence supports the view that primary olfactory cortical regions are not unimodal, but instead represent information from several sensory modalities - providing a substrate for sensory convergence early in olfactory processing. Adding to previous reports of both gustatory and visual influences on the cortical processing of odors, here we report novel findings revealing that the olfactory code is subject to auditory cross-modal influences. In vivo extracellular recordings from the olfactory tubercle, a trilaminar structure within the basal forebrain, of anesthetized mice revealed that olfactory tubercle single-units selectively respond to odors - with 65% of units showing significant odor-evoked activity. Remarkably, 19% of olfactory tubercle single-units also showed robust responses to an auditory tone. Furthermore, 29% of single-units tested displayed supra-additive or suppressive responses to the simultaneous presentation of odor and tone, suggesting cross-modal modulation. In contrast, olfactory bulb units did not show significant responses to tone presentation, nor modulation of odor-evoked activity by tone - suggesting a lack of olfactory- auditory convergence upstream from the olfactory tubercle. Thus, the tubercle presents itself as a source for direct multimodal convergence within an early stage of odor processing, and may serve as a seat for psychophysical interactions between smells and sounds

Odors that we encounter everyday are usually very complex. While the olfactory system is capable of discriminating complex yet similar odors (e.g. mocha and latte) with practice, the underlying mechanisms are not clear. As more data have been reported in anesthetized animals, data from awake animals are few. This experiment was therefore designed to investigate two related questions in awake rats: 1) odor coding of complex mixture in the anterior piriform cortex (a PCX) and 2) fear conditioning effects on odor coding in the a PCX. To record activity from awake animals, Long-Evans hooded rats were chronically implanted with movable bundles of microwires aimed at the a PCX. Up to 7 units were recorded simultaneously, and the electrode bundle was moved over time to sample additional cells. Odor-shock conditioning was performed to induce odor-related aversive experience on the rats, with a complex 10-odorant mixture as the conditioned stimulus (CS). The CS odor, along with overlapping odor mixtures and limonene were presented to the animals before the conditioning trials and for several days post-training. The results (n = 206 units) showed a slight decrease in percentage of units that showed excitation after conditioning, and a significant increase in suppression. A significant decrease in average spontaneous activity was observed after conditioning. Finally, an analysis of single-unit responsiveness revealed a late suppressive response after conditioning to all three mixtures overlapping with the CS but not limonene. Interestingly, while responsiveness to control odors decreased after conditioning, responses to the CS became temporally focused, with a more narrow range of onset and offset latencies. Together, odor fear conditioning should enhance signal:noise and CS coding acuity in a PCX

Sleep plays an active role in memory consolidation. Sleep structure (REM/ Slow-wave sleep [SWS]) is modified after conditioning, and in some cortical circuits, SWS is associated with replay of the learned experience. Interestingly, the sleep modifications can be local, only affecting activity in the brain regions active during the training. Here, we wanted to ascertain possible changes in sleep structure within olfactory cortex following odor fear conditioning. We recorded local field potentials (LFP) from the anterior piriform cortex (aPCX) in behaving animals and analyzed odor-evoked changes during fear conditioning and subsequent sleep structure modifications. Long-Evans hooded rats were chronically implanted with telemetry electrodes in the aPCX. Rats were placed in a conditioning box for 30 min on three baseline days, conditioned with ten paired odor-shock stimuli on the fourth day, and tested with five odor pulses on the fifth day. On the conditioning and test days, behavioral (freezing or vocalization), autonomic (heart rate) and LFP responses to the conditioned odor were examined. After each daily session, we placed the animal in a dark, sound attenuating chamber and recorded LFPs and EMG for 4 hours. Preliminary data show that rats learned behavioral and autonomic fear responses to the odor and that aPCX odor-evoked beta (15-40 Hz) oscillatory activity may correlate with the magnitude of the fear response. Furthermore, aPCX SWS increased following odor-shock conditioning compared to baseline days. Unpaired control rats showed neither odor fear responses nor an increase in SWS. Finally, the activity of aPCX single-units during SWS was shaped by recent odor experience and there was enhanced functional connectivity between the aPCX and hippocampus during SWS compared to other period

The most commonly cited descriptions of the behavioral characteristics of habituation come from two papers published almost 40 years ago [Groves, P. M., & Thompson, R. F. (1970). Habituation: A dual-process theory. Psychological Review, 77, 419-450; Thompson, R. F., & Spencer, W. A. (1966). Habituation: A model phenomenon for the study of neuronal substrates of behavior. Psychological Review, 73, 16-43]. In August 2007, the authors of this review, who study habituation in a wide range of species and paradigms, met to discuss their work on habituation and to revisit and refine the characteristics of habituation. This review offers a re-evaluation of the characteristics of habituation in light of these discussions. We made substantial changes to only a few of the characteristics, usually to add new information and expand upon the description rather than to substantially alter the original point

Olfaction represents an ideal model system for the study of mammalian habituation given that it is an anatomically relatively simple system with strong reciprocal connections to the limbic system, driving both reflexive and non-reflexive (motivated) behaviors that are easily quantifiable. Data are reviewed here demonstrating short-term habituation of the odor-evoked heart-rate orienting reflex described according to the criteria for habituation outlined by Thompson and Spencer [Thompson, R. F., & Spencer, W. A. (1966). Habituation: A model phenomenon for the study of neuronal substrates of behavior. Psychological Reviews, 73(1), 16-43]. A necessary and sufficient mechanism of short-term habituation is then described, which involves a metabotropic glutamate receptor mediated depression of afferent input to the piriform (primary olfactory) cortex. Finally, evidence for, and a mechanisms of, dishabituation of the orienting reflex and cortical adaptation are described