Faculty Bibliography

Learning to adapt to a complex and fluctuating environment requires the ability to adjust neural representations of sensory stimuli. Through pattern completion processes, cortical networks can reconstruct familiar patterns from degraded input patterns, whereas pattern separation processes allow discrimination of even highly overlapping inputs. Here we show that the balance between pattern separation and completion is experience dependent. Rats given extensive training with overlapping complex odorant mixtures showed improved behavioral discrimination ability and enhanced piriform cortical ensemble pattern separation. In contrast, behavioral training to disregard normally detectable differences between overlapping mixtures resulted in impaired piriform cortical ensemble pattern separation (enhanced pattern completion) and impaired discrimination. This bidirectional effect was not found in the olfactory bulb; it may be due to plasticity within olfactory cortex itself. Thus pattern recognition, and the balance between pattern separation and completion, is highly malleable on the basis of task demands and occurs in concert with changes in perceptual performance

Sensory processing is often regarded as a passive process in which biological receptors like photoreceptors and mechanoreceptors transduce physical energy into a neural code. Recent findings, however, suggest that: first, most sensory processing is active, and largely determined by motor/attentional sampling routines; second, owing to rhythmicity in the motor routine, as well as to its entrainment of ambient rhythms in sensory regions, sensory inflow tends to be rhythmic; third, attentional manipulation of rhythms in sensory pathways is instrumental to perceptual selection. These observations outline the essentials of an Active Sensing paradigm, and argue for increased emphasis on the study of sensory processes as specific to the dynamic motor/attentional context in which inputs are acquired

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 present study was an examination of state-dependent functional connectivity during spontaneous activity between the piriform cortex and its upstream and downstream connections. Rats were anesthetized with urethan and allowed to spontaneously cycle between fast- and slow-wave states similar to fast- and slow-wave sleep states. Local field potential recordings were made from the olfactory bulb, piriform cortex, dorsal hippocampus, amygdala, and primary visual cortex. The results demonstrate that during slow-wave sleep-like states, when the piriform cortex shows reduced sensitivity to odor input via the olfactory bulb, there is enhanced coherence with other forebrain structures. Granger causality analyses suggest that the link between piriform cortical and hippocampal activity during slow-wave state is in the direction of the hippocampus to the piriform cortex rather than the reverse. The results suggest that slow-wave sleep-like states may provide an opportunity for the transfer and/or consolidation of information related to odor memories, specifically at a time when the piriform cortex is less sensitive to sensory input

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

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

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