Comparison of odor receptive field plasticity in the rat olfactory bulb and anterior piriform cortex

Recent work in the anterior piriform cortex (aPCX) has demonstrated that cortical odor receptive fields are highly dynamic, showing rapid changes of both firing rate and temporal patterning within relatively few inhalations of an odor, despite relatively maintained, patterned input from olfactory bulb mitral/tufted cells. The present experiment examined the precision (odor-specificity) of this receptive field plasticity and compared it with the primary cortical afferent, olfactory bulb mitral/tufted cells. Adult Long-Evans hooded rats, urethan anesthetized and freely breathing, were used for single-unit recording from mitral/tufted and aPCX layer II/III neurons. Partial mapping of receptive fields to alkane odors (pentane, heptane, and nonane) was performed before and immediately after habituation (50-s exposure) to one of the alkanes. The results demonstrated that odor habituation of aPCX responses was odor specific, with minimal cross-habituation between alkanes differing by as few as two carbons. Mitral/tufted cells, however, showed strong cross-habituation within the odor set with the most profound cross effects to carbon chains shorter than the habituating stimulus. The results suggest that although mitral/tufted cells and aPCX neurons have roughly similar odor receptive fields, aPCX neurons have significantly better odor discrimination within their receptive field. The results have important implications for understanding the underlying bases of receptive fields in olfactory system neurons and the mechanisms of odor discrimination and memory.     

Generalized vs. stimulus-specific learned fear differentially modifies stimulus encoding in primary sensory cortex of awake rats

Experience shapes both central olfactory system function and odor perception. In piriform cortex, odor experience appears critical for synthetic processing of odor mixtures, which contributes to perceptual learning and perceptual acuity, as well as contributing to memory for events and/or rewards associated with odors. Here, we examined the effect of odor fear conditioning on piriform cortical single-unit responses to the learned aversive odor, as well as its effects on similar (overlapping mixtures) in freely moving rats. We found that odor-evoked fear responses were training paradigm dependent. Simple association of a condition stimulus positive (CS+) odor with foot shock (unconditioned stimulus) led to generalized fear (cue-evoked freezing) to similar odors. However, after differential conditioning, which included trials where a CS- odor (a mixture overlapping with the CS+) was not paired with shock, freezing responses were CS+ odor specific and less generalized. Pseudoconditioning led to no odor-evoked freezing. These differential levels of stimulus control over freezing were associated with different training-induced changes in single-unit odor responses in anterior piriform cortex (aPCX). Both simple and differential conditioning induced a significant decrease in aPCX single-unit spontaneous activity compared with pretraining levels while pseudoconditioning did not. Simple conditioning enhanced mean receptive field size (breadth of tuning) of the aPCX units, while differential conditioning reduced mean receptive field size. These results suggest that generalized fear is associated with an impairment of olfactory cortical discrimination. Furthermore, changes in sensory processing are dependent on the nature of training and can predict the stimulus-controlled behavioral outcome of the training.     

Chemical factors determine olfactory system beta oscillations in waking rats

Recent studies have pointed to olfactory system beta oscillations of the local field potential (15-30 Hz) and their roles both in learning and as specific responses to predator odors. To describe odorant physical properties, resultant behavioral responses and changes in the central olfactory system that may induce these oscillations without associative learning, we tested rats with 26 monomolecular odorants spanning 6 log units of theoretical vapor pressure (estimate of relative vapor phase concentration) and 10 different odor mixtures. We found odorant vapor phase concentration to be inversely correlated with investigation time on the first presentation, after which investigation times were brief and not different across odorants. Analysis of local field potentials from the olfactory bulb and anterior piriform cortex shows that beta oscillations in waking rats occur specifically in response to the class of volatile organic compounds with vapor pressures of 1-120 mmHg. Beta oscillations develop over the first three to four presentations and are weakly present for some odorants in anesthetized rats. Gamma oscillations show a smaller effect that is not restricted to the same range of odorants. Olfactory bulb theta oscillations were also examined as a measure of effective afferent input strength, and the power of these oscillations did not vary systematically with vapor pressure, suggesting that it is not olfactory bulb drive strength that determines the presence of beta oscillations. Theta band coherence analysis shows that coupling strength between the olfactory bulb and piriform cortex increases linearly with vapor phase concentration, which may facilitate beta oscillations above a threshold.     

Olfactory cortical adaptation facilitates detection of odors against background

Detection and discrimination of odors generally, if not always, occurs against an odorous background. On any given inhalation, olfactory receptor neurons will be activated by features of both the target odorant and features of background stimuli. To identify a target odorant against a background therefore, the olfactory system must be capable of grouping a subset of features into an odor object distinct from the background. Our previous work has suggested that rapid homosynaptic depression of afferents to the anterior piriform cortex (aPCX) contributes to both cortical odor adaptation to prolonged stimulation and habituation of simple odor-evoked behaviors. We hypothesize here that this process may also contribute to figure-ground separation of a target odorant from background stimulation. Single-unit recordings were made from both mitral/tufted cells and aPCX neurons in urethan-anesthetized rats and mice. Single-unit responses to odorant stimuli and their binary mixtures were determined. One of the odorants was randomly selected as the background and presented for 50 s. Forty seconds after the onset of the background stimulus, the second target odorant was presented, producing a binary mixture. The results suggest that mitral/tufted cells continue to respond to the background odorant and, when the target odorant is presented, had response magnitudes similar to that evoked by the binary mixture. In contrast, aPCX neurons filter out the background stimulus while maintaining responses to the target stimulus. Thus the aPCX acts as a filter driven most strongly by changing stimuli, providing a potential mechanism for olfactory figure-ground separation and selective reading of olfactory bulb output.     

Ontogeny of odor discrimination: a method to assess novel odor discrimination in neonatal rats.

Recent research using molecular and functional imaging techniques has demonstrated a highly precise spatial representation of odor quality in the rodent olfactory bulb, which is enhanced by extensive lateral inhibitory circuitry. Much of this olfactory bulb circuitry develops postnatally in the rat, leading to the prediction that behavioral discrimination of odor quality may also emerge postnatally. However, currently no behavioral paradigm has been identified to test this prediction. The present report describes the expression and habituation of odor-evoked heart rate-orienting responses in neonatal rats. The results demonstrate that odor-evoked-orienting responses can be observed at least as early as postnatal day 4 (PN 4), and in those animals showing orienting responses, habituation is constant throughout the postnatal period. Furthermore, the results suggest that examination of cross-habituation using this paradigm can be used to explore odor discrimination ability in neonates. These results lay the foundation for future studies of precise mapping of the ontogeny of novel odor discrimination.     

Estrous odors and sexually conditioned neutral odors activate separate neural pathways in the male rat

Olfactory stimuli play important roles in sexual behavior. Previous studies have demonstrated that both estrous odors and initially neutral odors paired with copulation influence the sexual behavior of male rats. The present study examines the pattern of neural activation as revealed by Fos immunoreactivity (Fos-IR) following exposure to bedding scented with either a neutral odor (almond) paired previously with copulation, estrous odors or no odor. Following exposure to estrous odors Fos-IR increased in the accessory olfactory bulb, medial amygdala, medial bed nucleus of the stria terminalis, medial preoptic area, ventromedial hypothalamus, ventral tegmental area, and both the nucleus accumbens core and shell. Conversely, following exposure to the sexually conditioned odor Fos-IR increased in the piriform cortex, basolateral amygdala, nucleus accumbens core, and the anterior portion of the lateral hypothalamic area. In addition, following exposure to almond odor Fos-IR increased in the main olfactory bulb independent of its pairing with copulation. These patterns of Fos-IR following exposure to estrous or sexually conditioned odors were not influenced by either the addition or omission of the other type of odor. These findings demonstrate that estrous and sexually conditioned odors are processed by distinct neural pathways and converge in the nucleus accumbens core, suggesting that this structure has a unique role in processing sexual stimuli of both pheromonal and olfactory natures.     

Enhanced synaptic responses in the piriform cortex associated with sexual stimulation in the male rat

Male rats that copulate to ejaculation with female rats bearing an odor show a learned preference to ejaculate selectively with females that bear the odor. This conditioned ejaculatory preference reflects an association between the odor and the reward state induced by ejaculation. Although little is known about the neuronal mechanisms that mediate this form of learning, convergence of genitosensory and olfactory inputs occurs in both hypothalamic and cortical regions, notably within primary olfactory (piriform) cortex, which may be involved in the encoding or storage of the association. The present study contrasted the ability of genital investigations, mounts, intromissions, ejaculations, and a sexually conditioned olfactory stimulus, to enhance evoked synaptic field potentials in the piriform cortex. Rats in the Paired group underwent conditioning trials in which they copulated with sexually receptive females bearing an almond odor. Rats in the Unpaired control group copulated with receptive females bearing no odor. Responses in the piriform cortex evoked by electrical stimulation of the olfactory bulb were recorded in male rats as they engaged in different aspects of sexual behavior, and were also recorded after conditioning, during exposure to cotton swabs bearing the almond odor. The monosynaptic component of responses was increased during intromission and ejaculation, and the late component of responses was increased during anogenital sniffing and mounting (with or without intromission). However, no differences in the amplitudes of evoked responses were found between the Paired and Unpaired groups, and no differences in synaptic responses were found during presentation of the odor after conditioning. These data indicate that short-term alterations in synaptic responsiveness occur in piriform cortex as a function of sexual stimulation in the male rat, but that responses are not significantly altered by a conditioned odor.     

Enrichment to odors improves olfactory discrimination in adult rats

The authors tested how prior odor enrichment affects the spontaneous discrimination of both preexposed and novel odors. Experimental rats were exposed to single odors or to pairs of similar or dissimilar odors for 1-hr periods twice daily over 20 days. Spontaneous discriminations between pairs of similar odors were tested before and after the odor exposure period using an olfactory habituation task. The authors found that (a) experimental rats did not spontaneously discriminate similar odor pairs before the exposure period, whereas they spontaneously discriminated them after the enrichment period, and (b) the improvement of performance was not selective for the odors used during enrichment. These results show that odor experience changes perception in the manner predicted based on other groups' electrophysiological experiments.     

Odor-concentration coding in the guinea-pig piriform cortex

By optical imaging of intrinsic signals, we demonstrated a possible code for odor concentration in the anterior piriform cortex of the guinea-pig. Odor-induced cortical activation, which primarily originated in layer II, appeared in a narrow band beneath the rhinal sulcus over the lateral olfactory tract, corresponding to the dorsal part of the anterior piriform cortex. Lower concentrations activated the rostral region of the band, whereas higher ones generated caudally spreading activation, and the site at which neural activation reached its maximum extent depended upon odor concentration. Different odors with low concentrations generated distinct but somewhat overlapping patterns in the rostral region of the band; the limited extent of cortical activity may be one focal domain for each odor. It was hard to judge, however, that odor-specific domains appeared in the anterior piriform cortex, because the strong stimuli induced largely overlapping patterns. Furthermore, the total area activated increased in proportion to concentrations raised to a power of 0.5-0.9. Importantly, these imaging results were confirmed with unit recordings which indicated a rostro-caudal gradient in odor-sensitivity among cortical neurons. Our results suggest that the dorsal part of the anterior piriform cortex may be associated with odor concentration. Therefore, in addition to recruitment of more olfactory sensory cells and glomeruli in response to stronger stimuli, a rostro-caudal gradient in axonal projections from mitral/tufted cells and/or in association fibers may play an important role in odor-concentration coding in the anterior piriform cortex.     

Age-associated loss of selectivity in human olfactory sensory neurons

We report a cross-sectional study of olfactory impairment with age based on both odorant-stimulated responses of human olfactory sensory neurons (OSNs) and tests of olfactory threshold sensitivity. A total of 621 OSNs from 440 subjects in 2 age groups of younger (≤ 45 years) and older (≥ 60 years) subjects were investigated using fluorescence intensity ratio fura-2 imaging. OSNs were tested for responses to 2 odorant mixtures, as well as to subsets of and individual odors in those mixtures. Whereas cells from younger donors were highly selective in the odorants to which they responded, cells from older donors were more likely to respond to multiple odor stimuli, despite a loss in these subjects' absolute olfactory sensitivity, suggesting a loss of specificity. This degradation in peripheral cellular specificity may impact odor discrimination and olfactory adaptation in the elderly. It is also possible that chronic adaptation as a result of reduced specificity contributes to observed declines in absolute sensitivity.     

Dissociated representations of irritation and valence in human primary olfactory cortex

Irritation and negative valence are closely associated in perception. However, these perceptual aspects can be dissociated in olfaction where irritation can accompany both pleasant and unpleasant odorants. Whereas the sensation of odor reflects transduction at olfactory receptors, irritation reflects concurrent transduction of the odorant at trigeminal receptors. Thus a stimulus can be either a pure olfactant activating the olfactory receptors only or a bimodal odorant activating both types of receptors. Using event-related functional magnetic resonance imaging and a 2 x 2 experimental design contrasting odorant valence (pleasant/unpleasant) and odorant type (pure olfactant/bimodal) we found activity in piriform cortex to be associated with valence, and not type, of odors. In contrast, activity in the olfactory tubercle was associated with type, and not valence, of odors. Importantly, this was found when perceived intensity was held equal across odorants. These findings suggest that dissociable neural substrates subserve the encoding of irritation and valence in olfaction.     

The paternally expressed gene Peg3 regulates sexual experience-dependent preferences for estrous odors

Sexual experience has marked and long-lasting effects on male behavior in mammals, regulating traits such as the anticipation and display of sexual behavior, aggression, and olfaction. The authors conducted urine preference, habituation-dishabituation, and partner choice tests with sexually experienced and naive male mice and found that wild-type males acquire adaptively significant preferences for the odors of receptive, estrous females with sexual experience, and that these preferences are matched by changes in main olfactory system responses involving the piriform cortex, as indicated by c-Fos expression. The authors also report that these experiential effects are disrupted in male mice carrying a knockout of the imprinted gene Peg3. This paternally expressed gene regulates maternal care and offspring development, but the authors here report that Peg3 mutant males suffer a complex olfactory deficit that affects estrous odor preferences and the responses of the main olfactory system to such odors. Peg3 appears to have evolved to regulate the experience-dependent preference for receptive females, an adaptive trait that would enhance male reproductive success and so potentially increase paternal transmission of this paternally expressed gene.     

Functional mapping of human brain in olfactory processing: a PET study

This study describes the functional anatomy of olfactory and visual naming and matching in humans, using positron emission tomography (PET). One baseline control task without olfactory or visual stimulation, one control task with simple olfactory and visual stimulation without cognition, one set of olfactory and visual naming tasks, and one set of olfactory and visual matching tasks were administered to eight normal volunteers. In the olfactory naming task (ON), odors from familiar items, associated with some verbal label, were to be named. Hence, it required long-term olfactory memory retrieval for stimulus recognition. The olfactory matching task (OM) involved differentiating a recently encoded unfamiliar odor from a sequentially presented group of unfamiliar odors. This required short-term olfactory memory retrieval for stimulus differentiation. The simple olfactory and visual stimulation resulted in activation of the left orbitofrontal region, the right piriform cortex, and the bilateral occipital cortex. During olfactory naming, activation was detected in the left cuneus, the right anterior cingulate gyrus, the left insula, and the cerebellum bilaterally. It appears that the effort to identify the origin of an odor involved semantic analysis and some degree of mental imagery. During olfactory matching, activation was observed in the left cuneus and the cerebellum bilaterally. This identified the brain areas activated during differentiation of one unlabeled odor from the others. In cross-task analysis, the region found to be specific for olfactory naming was the left cuneus. Our results show definite recruitment of the visual cortex in ON and OM tasks, most likely related to imagery component of these tasks. The cerebellar role in cognitive tasks has been recognized, but this is the first PET study that suggests that the human cerebellum may have a role in cognitive olfactory processing as well.     

Non-specific olfactory aversion induced by intrabulbar infusion of the GABA(A) receptor antagonist bicuculline in young rats

On postnatal day 12, young rats show an aversion to an odor to which they had been exposed along with presentations of foot shock on postnatal day 11. The acquisition of this aversive learning involves and requires disinhibition of the mitral/tufted cells induced by centrifugal noradrenergic activation during somatosensory stimulation. This olfactory learning is established only for the odor to which the rat has been exposed during conditioning. Infusion of the GABA(A) receptor antagonist bicuculline at a high dose (2.0 nmol/each olfactory bulb) into the olfactory bulb in the presence of an odor is capable of developing olfactory aversive responses without somatosensory stimulation in young rats. The purpose of this study is to characterize the properties of bicuculline-induced aversive responses. In contrast to the odor specificity of aversive learning produced by odor-shock conditioning, bicuculline-induced aversive responses lack odor specificity. Namely, bicuculline infusion in the presence of a citral odor results, in a dose-dependent manner, in subsequent aversive responses to strange odors (benzaldehyde and vanillin) that have never been presented. Moreover, bicuculline infusion alone is sufficient to produce dose-dependent aversive responses to strange odors (citral, benzaldehyde and geraniol).From these results we suggest that disinhibition of mitral/tufted cells from granule cells by bicuculline infusion makes young rats aversive to strange odors non-specifically, as if the rats had learned the odor aversion as a result of odor exposure paired with foot shock. Different mechanisms of disinhibition of the mitral/tufted cells may underlie both the pharmacological manipulation and noradrenergic activation by somatosensory stimulation.     

Orbital cortex neuronal responses during an odor-based conditioned associative task in rats

Neuronal activity in the rat orbital cortex during discrimination of various odors [five volatile organic compounds (acetophenone, isoamyl acetate, cyclohexanone, p-cymene and 1,8-cineole), and food- and cosmetic-related odorants (black pepper, cheese, rose and perfume)] and other conditioned sensory stimuli (tones, light and air puff) was recorded and compared with behavioral responses to the same odors (black pepper, cheese, rose and perfume). In a neurophysiological study, the rats were trained to lick a spout that protruded close to its mouth to obtain sucrose or intracranial self-stimulation reward after presentation of conditioned stimuli. Of 150 orbital cortex neurons recorded during the task, 65 responded to one or more types of sensory stimuli. Of these, 73.8% (48/65) responded during presentation of an odor. Although the mean breadth of responsiveness (entropy) of the olfactory neurons based on the responses to five volatile organic compounds and air (control) was rather high (0.795), these stimuli were well discriminated in an odor space resulting from multidimensional scaling using Pearson's correlation coefficients between the stimuli. In a behavioral study, a rat was housed in an equilateral octagonal cage, with free access to food and choice among eight levers, four of which elicited only water (no odor, controls), and four of which elicited both water and one of four odors (black pepper, cheese, rose or perfume). Lever presses for each odor and control were counted. Distributions of these five stimuli (four odors and air) in an odor space derived from the multidimensional scaling using Pearson's correlation coefficients based on behavioral responses were very similar to those based on neuronal responses to the same five stimuli. Furthermore, Pearson's correlation coefficients between the same five stimuli based on the neuronal responses and those based on behavioral responses were significantly correlated. The results demonstrated a pivotal role of the rat orbital cortex in olfactory sensory processing and suggest that the orbital cortex is important in the manifestation of various motivated behaviors of the animals, including odor-guided motivational behaviors (odor preference).     

Olfactory-evoked regional cerebral blood flow in Alzheimer's disease

Olfaction is impaired in Alzheimer's disease (AD). It was hypothesized that AD would reduce olfactory-evoked perfusion in mesial temporal olfactory (piriform) cortex, where neuropathology begins. Seven AD patients and 8 elderly controls (ECs) underwent olfactory threshold and identification tests and olfactory stimulation during positron emission tomography. Odor identification was impaired in AD, but threshold was not. Olfactory stimulation in ECs activated right and left piriform areas and right anterior ventral temporal cortex. AD patients had less activation in right piriform and anterior ventral temporal cortex but not in the left piriform area. Although orbital cortex did not activate in ECs, there was a significant between-groups difference in this area. Right piriform activation correlated with odor identification. Impaired odor identification likely reflects sensory cortex dysfunction rather than cognitive impairment. Given olfactory bulb projections to the mesial temporal lobe, olfactory stimulation during functional imaging might detect early dysfunction in this region.     

Orbital cortex neuronal responses during an odor-based conditioned associative task in rats

Neuronal activity in the rat orbital cortex during discrimination of various odors [five volatile organic compounds (acetophenone, isoamyl acetate, cyclohexanone, p-cymene and 1,8-cineole), and food- and cosmetic-related odorants (black pepper, cheese, rose and perfume)] and other conditioned sensory stimuli (tones, light and air puff) was recorded and compared with behavioral responses to the same odors (black pepper, cheese, rose and perfume). In a neurophysiological study, the rats were trained to lick a spout that protruded close to its mouth to obtain sucrose or intracranial self-stimulation reward after presentation of conditioned stimuli. Of 150 orbital cortex neurons recorded during the task, 65 responded to one or more types of sensory stimuli. Of these, 73.8% (48/65) responded during presentation of an odor. Although the mean breadth of responsiveness (entropy) of the olfactory neurons based on the responses to five volatile organic compounds and air (control) was rather high (0.795), these stimuli were well discriminated in an odor space resulting from multidimensional scaling using Pearson's correlation coefficients between the stimuli. In a behavioral study, a rat was housed in an equilateral octagonal cage, with free access to food and choice among eight levers, four of which elicited only water (no odor, controls), and four of which elicited both water and one of four odors (black pepper, cheese, rose or perfume). Lever presses for each odor and control were counted. Distributions of these five stimuli (four odors and air) in an odor space derived from the multidimensional scaling using Pearson's correlation coefficients based on behavioral responses were very similar to those based on neuronal responses to the same five stimuli. Furthermore, Pearson's correlation coefficients between the same five stimuli based on the neuronal responses and those based on behavioral responses were significantly correlated.The results demonstrated a pivotal role of the rat orbital cortex in olfactory sensory processing and suggest that the orbital cortex is important in the manifestation of various motivated behaviors of the animals, including odor-guided motivational behaviors (odor preference).     

Rapid,experience-induced enhancement in odorant discrimination by anterior piriform cortex neurons

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.     

Similar increases in extracellular lactic acid in the limbic system during epileptic and/or olfactory stimulation

Previous studies have shown that physiological stimulation of brain activity increases anaerobic glucose consumption, both in humans and in experimental animals. To investigate this phenomenon further, we measured extracellular lactate levels within different rat brain regions, using microdialysis. Experiments were performed comparing the effects of natural, physiological olfactory stimulation of the limbic system with experimental limbic seizures. Olfactory stimulation was carried out by using different odors (i.e. both conventional odors: 2-isobutyl-3-methoxypyrazine, green pepper essence; thymol; and 2-sec-butylthiazoline, a sexual pheromone). Limbic seizures were either induced by systemic injection of pilocarpine (200-400 mg/kg) or focally elicited by microinfusions of chemoconvulsants (bicuculline 118 pmol and cychlothiazide 1.2 nmol) within the anterior piriform cortex. Seizures induced by systemic pilocarpine tripled lactic acid within the hippocampus, whereas limbic seizures elicited by focal microinfusion of chemoconvulsants within the piriform cortex produced a less pronounced increase in extracellular lactic acid. Increases in extracellular lactate occurring during olfactory stimulation with the sexual pheromone (three times the baseline levels) were non-significantly different from those occurring after systemic pilocarpine. Increases in lactic acid following natural olfactory stimulation were abolished both by olfactory bulbectomy and by the focal microinfusion of tetrodotoxin, while they were significantly attenuated by the local application of the N-methyl-D-aspartate antagonist AP-5. Increases in hippocampal lactate induced by short-lasting stimuli (olfactory stimulation or microinfusion of subthreshold doses of chemoconvulsants, bicuculline 30 pmol) were reproducible after a short delay (1 h) and cumulated when applied sequentially. In contrast, limbic status epilepticus led to a long-lasting refractoriness to additional lactate-raising stimuli and there was no further increase in lactate levels when the olfactory stimulation was produced during status epilepticus. Increases in lactic acid following olfactory stimulation occurred with site specificity in the rhinencephalon (hippocampus, piriform and entorhinal cortex) but not in the dorsal striatum. Site specificity crucially relied on the quality of the stimulus. For instance, other natural stimuli (i.e. tail pinch) produced a similar increase in extracellular lactate in all brain areas under investigation.The major conclusion of this work is that the presentation of an odor known to be a rat pheromone results in lactate production as great as that induced by the systemic convulsant pylocarpine (maximum: 2.286+/-0.195 mM and 1.803+/-0.108 mM, respectively). This supports the notion that the great magnitude of lactate production known to accompany seizures can result from the intensified neural activity per se ("aerobic gycolysis"), not merely from local anoxia or other pathological changes.     

Neurobehavioral consequences of cortical adaptation disruption during ontogeny

Filtering of redundant or stable inputs is a critical function of all sensory pathways. Normal sensory gating can allow processing resources to be differentially devoted to changing or otherwise biologically significant stimuli. In olfaction, short-term odor habituation is mediated by a metabotropic glutamate receptor (mGluR)-mediated depression of afferent synapses in the piriform cortex. Given the role of early experience in shaping cortical function and anatomy, the present experiments examined the effects of chronic habituation disruption during development on behavior and local circuit anatomy. Rats were chronically intra-cerebrally infused with the mGluR group III antagonist (RS)-a-cyclopropyl-4-phosphonophenylglycine (CPPG) during early development. The results demonstrated that early onset mGluRIII blockade resulted in a long-lasting decrement in odor habituation compared to controls, evident for at least 2 weeks post-infusion offset. Odor investigation time in the youngest animals was correlated with cortical laminar thickness, though the long-lasting behavioral effect showed no such correlation. No changes in apical dendritic spine density in the piriform cortex were detected. Combined with previous work, these results suggest that sensory gating disruption during development can have both immediate and long-lasting effects on sensory-guided behavior.