Faculty Bibliography

Anterior piriform cortex (aPCX) neurons rapidly filter repetitive odor stimuli despite relatively maintained input from mitral cells. This cortical adaptation is correlated with short-term depression of afferent synapses, in vivo. The purpose of this study was to elucidate mechanisms underlying this nonassociative neural plasticity using in vivo and in vitro preparations and to determine its role in cortical odor adaptation. Lateral olfactory tract (LOT)-evoked responses were recorded in rat aPCX coronal slices. Extracellular and intracellular potentials were recorded before and after simulated odor stimulation of the LOT. Results were compared with in vivo intracellular recordings from aPCX layer II/III neurons and field recordings in urethane-anesthetized rats stimulated with odorants. The onset, time course, and extent of LOT synaptic depression during both in vitro electrical and in vivo odorant stimulation methods were similar. Similar to the odor specificity of cortical odor adaptation in vivo, there was no evidence of heterosynaptic depression between independent inputs in vitro. In vitro evidence suggests at least two mechanisms contribute to this activity-dependent synaptic depression: a rapidly recovering presynaptic depression during the initial 10-20 sec of the post-train recovery period and a longer lasting (approximately 120 sec) depression that can be blocked by the metabotropic glutamate receptor (mGluR) II/III antagonist (RS)-alpha-cyclopropyl-4-phosphonophenylglycine (CPPG) and by the beta-adrenergic receptor agonist isoproterenol. Importantly, in line with the in vitro findings, both adaptation of odor responses in the beta (15-35 Hz) spectral range and the associated synaptic depression can also be blocked by intracortical infusion of CPPG in vivo.

Olfactory perceptual learning is a relatively long-term, learned increase in perceptual acuity, and has been described in both humans and animals. Data from recent electrophysiological studies have indicated that olfactory perceptual learning may be correlated with changes in odorant receptive fields of neurons in the olfactory bulb and piriform cortex. These changes include enhanced representation of the molecular features of familiar odors by mitral cells in the olfactory bulb, and synthetic coding of multiple coincident odorant features into odor objects by cortical neurons. In this paper, data are reviewed that show the critical role of acetylcholine (Ach) in olfactory system function and plasticity, and cholinergic modulation of olfactory perceptual learning at both the behavioral and cortical level

Previous work has identified a population of neurons within the anterior piriform cortex that undergo rapid apoptosis following de-afferentation by olfactory bulbectomy in adult rats. The specific initiation signal for apoptosis in this paradigm is unknown, but may include an activity-dependent trans-neuronal cascade. The present report examined the effect of adult-onset unilateral naris occlusion, which reduces olfactory bulb afferent excitation of piriform cortex, on apoptosis (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling [TUNEL]) in the rat anterior piriform cortex. Adult Long-Evans hooded rats received unilateral naris occlusion or a control manipulation and were sacrificed after 1, 5, 7, 10 or 20 days later. For comparison, a second group of rats received a unilateral bulbectomy and were sacrificed 24 h later. Counts of TUNEL-stained cell profiles were performed for layers I/II and layer III of the anterior piriform cortex ipsilateral and contralateral to the manipulation. The results confirmed that unilateral bulbectomy produced a dramatic increase in TUNEL labeling in layers I/II of the ipsilateral piriform cortex 24 h after bulbectomy. Unilateral naris closure also produced enhanced TUNEL labeling, although the magnitude of the effect was less than that produced by bulbectomy, and enhanced TUNEL labeling was apparent both ipsilateral and contralateral to the sealed naris compared to controls. Deprivation-induced TUNEL labeling was detectable by 24 h post-closure, peaked at 5 days and was no different from controls by 20 days post-closure. Neither bulbectomy nor naris closure affected TUNEL labeling in layer III. Together, these results suggest that there is a population of superficial cells in piriform cortex whose survival is tightly regulated by sensory input

The major problem in olfactory neuroscience is to determine how the brain discriminates one odorant from another. The traditional approach involves identifying how particular features of a chemical stimulus are represented in the olfactory system. However, this perspective is at odds with a growing body of evidence, from both neurobiology and psychology, which places primary emphasis on synthetic processing and experiential factors--perceptual learning--rather than on the structural features of the stimulus as critical for odor discrimination. In the present review of both psychological and sensory physiological data, we argue that the initial odorant feature extraction/analytical processing is not behaviorally/consciously accessible, but rather is a first necessary stage for subsequent cortical synthetic processing which in turn drives olfactory behavior. Cortical synthetic coding reflects an experience-dependent process that allows synthesis of novel co-occurring features, similar to processes used for visual object coding. Thus, we propose that experience and cortical plasticity are not only important for traditional associative olfactory memory (e.g. fear conditioning, maze learning, and delayed-match-to-sample paradigms), but also play a critical, defining role in odor discrimination

Olfactory system second-order neurons, mitral-tufted cells, have odorant receptive fields (ORFs) (molecular receptive ranges in odorant space for carbon chain length in organic odorant molecules). This study quantified several dimensions of these excitatory odorant receptive fields to novel odorants in rats and then examined the effects of passive odorant exposure on the shape of the ORF-tuning curve. ORFs for carbon chain length of novel ethyl esters (pure odorants that the animals had not been exposed to previously) were determined before and after a 50 sec prolonged exposure to one of the odorants. In response to novel odorants, quantitative analysis of mitral-tufted cell excitatory ORFs revealed that the median ORF width spanned 3-4 carbons, generally with a single-most excitatory odorant. Exposure to either the most excitatory odorant (ON-PEAK) or an odorant that was two carbons longer (OFF-PEAK) for 50 sec produced whole ORF suppression immediately after the end of the prolonged exposure, with the ON-PEAK exposure producing the greatest suppression. These results are consistent with a feature-detecting function for mitral-tufted cells. Redetermination of the ORF 15 and 60 min after the exposure revealed that OFF-PEAK exposure produced a reduction in responsiveness to the best odorant and an increase in responsiveness to the exposed odorant. In contrast, exposure to the ON-PEAK odorant or no odorant did not affect ORFs. Given that mitral-tufted cells receive exclusive excitatory input from olfactory receptor neurons expressing identical receptor proteins, it is hypothesized that experience-induced mitral-tufted cell ORF changes reflect modulation of lateral and centrifugal olfactory bulb circuits

Current views of odorant discrimination by the mammalian olfactory system suggest that the piriform cortex serves as a site of odor object synthesis. Given the enormous number of odorant feature combinations possible in nature, however, it seems unlikely that cortical synthetic receptive fields (RFs) are innate but rather require experience for their formation. The present experiment addressed two issues. First, we made a direct comparison of mitral/tufted cell and anterior piriform cortex (aPCX) neuron abilities to discriminate odorant mixtures from their components to further test whether aPCX neurons can treat collections of features different from the features themselves (synthetic coding). Second, we attempted to determine the minimum duration of experience necessary for formation of cortical synthetic RFs. Single-unit recordings were made from mitral/tufted cells and aPCX layer II/III neurons in urethan-anesthetized rats. Cross-habituation between novel binary mixtures and their novel components was used to determine odor discrimination abilities. The results suggest that after >/=50 s of experience with a binary mixture, aPCX neurons can discriminate the mixture from its components, whereas mitral/tufted cells cannot. However, when limited to 10 s of experience with the mixture, aPCX neurons appear similar to mitral/tufted cells and do not discriminate mixtures from components. These results suggest experience-dependent synthetic processing in aPCX and suggest an important role for perceptual learning in normal odor discrimination

Current emphasis on odorant physiochemical features as the basis for perception largely ignores the synthetic and experience-dependent nature of olfaction. Olfaction is synthetic, as mammals have only limited ability to identify elements within even simple odor mixtures. Furthermore, olfaction is experience-bound, as exposure alone can significantly affect the extent to which stimuli can be discriminated. We propose that early analytical processing of odors is inaccessible at the behavioral level and that all odors are initially encoded as 'objects' in the piriform cortex. Moreover, we suggest that odor perception is wholly dependent on the integrity of this memory system and that its loss severely impairs normal perception

Male and female rats underwent unilateral naris occlusion or sham surgery on either post-natal day (PN) 1 or after PN30. Following at least 30 days of unilateral olfactory deprivation, rats were urethane anesthetized and recordings were made from anterior piriform cortex (aPCX). Shock stimulation of afferent fibers (lateral olfactory tract) and association/commissural fibers evoked field potentials in aPCX that were analyzed across groups and between ages. The results demonstrate that early-onset unilateral olfactory deprivation depresses field potentials evoked by stimulation of the deprived cortical afferent, while late-onset deprivation did not. In contrast, intracortical association fiber mediated field potentials in the deprived cortex were enhanced after both early-onset and late-onset deprivation. These results suggest differential developmental plasticity of afferent and association fiber pathways in paleocortex that mirrors that previously described in neocortical sensory systems