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PubMed1976

Anaesthetics depress the sensitivity of cortical neurones to L-glutamate.

1 The effects of general anaesthetics on the responses of neurones to iontophoretically applied L-glutamate have been examined in slices of the guinea-pig olfactory cortex in vitro. 2 Concentrations of pentobarbitone, ether, methoxyflurance, trichloroethylene and alphaxalone that are known to depress synaptic transmission in the prepiriform cortex also depressed the sensitivity of prepiriform neurones to L-glutamate. 3 Halothane, in concentrations that depress synaptic transmission (less than 1%) did not alter sensitivity of neurones to glutamate. Higher concentrations (greater than 1% produced a dose-related depression of the glutamate sensitivity of neurones. 4 All four volatile anaesthetics tested caused some cells to alter their glutamate-evoked firing pattern to one in which the spike discharges were more closely grouped. Pentobarbitone and alphaxalone had no such effect. 5 If the sensitivity of the neurones to the endogenous excitatory transmitter is affected by anaesthetics in the same way as the glutamate-sensitivity, these results suggest that halothane depresses synaptic transmission by decreasing the amount of transmitter released from the nerve terminals, whereas the other anaesthetics depress the sensitivity of the post-synaptic membrane to the released transmitter.

Acetylcholine↗
PubMed1978

Catecholamine innervation of the basal forebrain. III. Olfactory bulb, anterior olfactory nuclei, olfactory tubercle and piriform cortex.

The catecholamine innervation of the olfactory bulb, anterior olfactory nuclei, olfactory tubercle and piriform cortex was studied in the rat using biochemical analysis and fluorescence histochemistry. Biochemical studies demonstrate a moderate norepinephrine (NE) content in all olfactory structures, a high dopamine (DA) content in the olfactory tubercle and a low DA content in the olfactory bulb, anterior olfactory nucleus and piriform cortex. Following locus coeruleus lesions NE content decreases 71% in the olfactory bulb, 82% in the anterior olfactory nucleus, 62% in olfactory tubercle and 77% in piriform cortex...

Amygdala↗
PubMed1996

The effects of olfactory and somatosensory desensitization on Fos-like immunoreactivity in the brains of pup-exposed postpartum rats.

Fos-like immunoreactivity (fos-lir) was examined in sites within the "maternal circuit" in postpartum female rats that received various sensory desensitizations and were exposed to pups for 1 or 2 hr. Neither olfactory bulbectomy nor thelectomy (nipple removal) significantly reduced the fos-lir in the anterior medial preoptic area (MPOA), although reductions following bulbectomy in medial amygdala did occur. Peripherally induced hyposmia by ZnSo4 reduced fos-lir in the olfactory structures (olfactory bulbs, piriform cortex, and olfactory tubercle), in medial and cortical nuclei of the amygdala, but not in anterior MPOA. Application of the topical anesthetic Emla to the ventrum only reduced fos-lir in the somatosensory cortex. Combined olfactory and ventral desensitizations produced marginal reductions in posterior MPOA. It is suggested that the MPOA is primarily involved as part of the effector system in the expression of the behavior. In contrast, the amygdala is involved in processing sensory cues received from pups during dam-litter interactions.

Afferent Pathways↗
PubMed2001

Cell activity in the anterior piriform cortex during an olfactory learning in the rat.

Several studies have shown that the piriform cortex is involved in learning processes and pyramidal cell activity does not only encode the odour quality but is also related to contextual information about past experience and future action. To study how odour-specific patterns in neuronal activity are established we used an odour discrimination go/no go task with water reinforcement for analysing extracellular single cell activity in anterior piriform cortex in freely moving rats. During conditioning single cells responded to different task events. Of the cells 52% participate in odour sampling and 87% were involved in odour discrimination. More than half of the responses to odours were inhibitory responses. Seventeen percent changed their activity for nose-poke only. The activity of 33% was related to reinforcement. Once established the pattern of reaction to the odour was preserved for several days. It is suggested that the anterior part of the piriform cortex is not involved in odour coding only. However, learning-related plasticity was not observed in this area.

Animals↗
PubMed1985

Aging in the rat olfactory system: relative stability of piriform cortex contrasts with changes in olfactory bulb and olfactory epithelium.

Previous studies have quantified growth and atrophy of the olfactory bulb and olfactory epithelium of the Sprague-Dawley rat from maturity to senescence. Major events occurring in these structures include changes in the volume of mitral cells and changes in the number of septal olfactory receptors. These effects are large, consist of a growth phase followed by atrophy, and are temporally related in that events in the olfactory epithelium precede those in the mitral cells. A hypothesis of aging based on transneuronal effects would predict that these changes would be similarly transmitted to the next synaptic station in the olfactory pathway. Therefore, cells and synapses of the piriform cortex were studied in rats 3, 12, 18, 24, 27, 30, and 33 months of age. Alternate Vibratome sections through brains perfused with mixed aldehydes were processed for light and electron microscopy. No significant age effects were found for the volumes of cortical laminae Ia and Ib. Both numerical and surface density of synaptic apposition zones in layer Ia, formed primarily by mitral cell axons, were stable with age. A modest (18%) but significant decline in the proportion of layer Ia occupied by dendrites and spines was mirrored by an increase in the proportion of glial processes; no change in the proportion of axons and terminals was observed. Neither nuclear volume, nor soma volume, nor numerical density of layer II neurons changed with age. Thus, contacts made in the piriform cortex by mitral cell axons remain relatively stable in senescence, despite the marked volumetric changes in the mitral cell somata, changes which were confirmed again in this study. Age-related dendritic regression in layer II neurons may be attributable to functional deafferentation subsequent to reduced receptor input to mitral cells.

Age Factors↗
PubMed1996

Orbitofrontal cortex neurons: role in olfactory and visual association learning.

1. The orbitofrontal cortex is implicated in the rapid learning of new associations between visual stimuli and primary reinforcers such as taste. It is also the site of convergence of information from olfactory, gustatory, and visual modalities. To investigate the neuronal mechanisms underlying the formation of odor-taste associations, we made recordings from olfactory neurons in the orbitofrontal cortex during the performance of an olfactory discrimination task and its reversal in macaques. 2. It was found that 68% of odor-responsive neurons modified their responses after the changes in the taste reward associations of the odorants. Full reversal of the neuronal responses was seen in 25% of these neurons. Extinction of the differential neuronal responses after task reversal was seen in 43% of these neurons. 3. For comparison, visually responsive orbitofrontal neurons were tested during reversal of a visual discrimination task. Seventy-one percent of these visual cells showed rapid full reversal of the visual stimulus to which they responded, when the association of the visual with taste was reversed in the reversal task. 4. These demonstrate that of many orbitofrontal cortex olfactory neurons on the taste with which the odor is associated. 5. This modification is likely to be important for setting the motivational value of olfactory for feeding and other rewarded behavior. However, it is less complete, and much slower, than the modifications found or orbit frontal visual during visual-taste reversal. This relative inflexibility of olfactory responses is consistent with the need for some stability is odor-taste associations to facilitate the formation and perception of flavors.

Acoustic Stimulation↗
PubMed1997

Distribution of RGS4 mRNA in mouse brain shown by in situ hybridization.

RGS proteins (regulators of G protein signaling) are a newly identified group of proteins that negatively regulate G proteins. Some, including RGS4, have been shown to act as GTPase-activating proteins for several members of the Gi alpha subunits and the Gq alpha subunit. However, the signaling pathways of G protein-coupled receptors regulated by RGS4 are not well understood. We isolated the mouse RGS4 cDNA to investigate the roles of RGS4 protein in mouse brain. Expression of mouse RGS4 in yeast stimulated adaptation to mating pheromone, suggesting that it negatively regulates that G protein-mediated signaling pathway. Northern blot analysis of various mouse tissues revealed that RGS4 is expressed at high levels in brain, moderately low levels in heart, and very low levels in lung, liver, and skeletal muscle. In situ hybridization of mouse brain showed RGS4 mRNA mainly in the cerebral cortex, hippocampus, anterior olfactory nucleus, piriform cortex, olfactory tubercle, caudate-putamen, nucleus accumbens, islands of Calleja, substantia nigra, amygdala, the granular layer of cerebellum, middle cerebellar peduncle, and perifacial zone. These results suggest that RGS4 is expressed in various types of cells in the brain and may regulate multiple G protein-mediated signaling pathways.

Animals↗
PubMed1990

The differential expression patterns of the mRNAs encoding beta subunits (beta 1, beta 2 and beta 3) of GABAA receptor in the olfactory bulb and its related areas in the rat brain.

The expression of mRNAs encoding different beta subunits (beta 1, beta 2 and beta 3) of GABAA receptor in the rat olfactory bulb and some of its related areas was investigated by in situ hybridization histochemistry. The beta 3 subunit mRNA was expressed in most of the cells in these regions such as periglomerular cells, tufted cells, mitral cells and granule cells in olfactory bulb, and the cells in anterior olfactory nucleus, piriform cortex and olfactory tubercle. However, only several kinds of these cells contained beta 2 subunit mRNA such as tufted cells and mitral cells of olfactory bulb, and the cells in anterior olfactory nucleus and piriform cortex. The beta 1 subunit mRNA was only detected in the mitral cells of olfactory bulb.

Animals↗
PubMed1998

Chronic phencyclidine induces behavioral sensitization and apoptotic cell death in the olfactory and piriform cortex.

In this study, we tested the hypothesis that chronic administration of phencyclidine (PCP), an N-methyl-D-aspartate (NMDA) receptor antagonist, would cause a long-lasting behavioral sensitization associated with neuronal toxicity. Female Sprague-Dawley rats were administered PCP (20 mg/kg, i.p.) once a day for 5 days, withdrawn for 72 hr, placed in locomotor activity chambers, and challenged with 3.2 mg/kg PCP. Following assessment of locomotor activity, the rats were killed and their brains processed for analysis of apoptosis by either electron microscopy or terminal dUTP nick-end labeling (TUNEL). In study I, PCP challenge produced a much more robust and long-lasting increase in locomotor activity in rats chronically treated with PCP than in those chronically treated with saline. In study II, clozapine pretreatment blunted the degree of sensitization caused by PCP. In study I, a marked increase in TUNEL-positive neurons was found in layer II of the olfactory tubercle and piriform cortex of rats chronically treated with PCP. Many of these neurons had crescent-shaped nuclei consistent with apoptotic condensation and margination of nuclear chromatin under the nuclear membrane. Acute PCP had no effect. Electron microscopy revealed that PCP caused nuclear condensation and neuronal degeneration consistent with apoptosis. Cell counts in layer II of the piriform cortex revealed that chronic PCP treatment resulted in the loss of almost 25% of the cells in this region. However, an increase in glial fibrillary acidic protein (GFAP)-positive cells in the molecular layer suggests that this neurotoxicity also may involve necrosis. In study II, the PCP-induced neuronal degeneration was essentially completely abolished by clozapine pretreatment. This pattern of degeneration was found to coincide with the distribution of the mRNA of the NR1 subunit of the NMDA receptor. The relevance of these data to a PCP model of chronic NMDA receptor hypofunction is discussed.

Animals↗
PubMed2000

Convergence of segregated pheromonal pathways from the accessory olfactory bulb to the cortex in the mouse.

The accessory olfactory system mediates intraspecies pheromonal communication. Two subsets of spatially segregated vomeronasal sensory neurons, presumably handling functionally and structurally different sets of ligand molecules, can be distinguished. The two subsets of sensory neurons project their axons to segregated zones of the accessory olfactory bulb (AOB) and connect with zonally separated mitral/tufted (M/T) cells, suggesting that the accessory olfactory system is divided into two distinct pathways up to the level of the AOB. To examine whether the segregation is maintained at the accessory olfactory cortical (AOC) regions, we selectively tracer-labelled mitral/tufted cells located in the rostral, caudal or in both zones of the adult mouse AOB. The results demonstrate that the axonal projection patterns of rostral zone and caudal zone M/T cells were indistinguishable in the AOC regions. Mitral/tufted cell axons from either zone of the AOB covered the entire area of all four AOC regions: the bed nucleus of the accessory olfactory tract, the medial amygdaloid nucleus, the posteromedial cortical amygdaloid nucleus and the bed nucleus of the stria terminalis. Therefore, over the entire area of each AOC region, ensembles of cortical neurons receive input from both zonal subsets of M/T cells of the AOB. However, the present results do not rule out the possibility that individual cortical neurons sample information from M/T cells of a single zone. These results are consistent with the idea that the segregation of zonal pathways collapses in the AOC regions. Clusters of cortical neurons in each AOC region may combine information from both families of pheromone receptors and thus handle signals from structurally and functionally different categories of pheromone molecules.

Animals↗
PubMed1993

Organization of cortical afferent input to orbitofrontal areas in the rhesus monkey.

Odorant signal processing takes place in a diverse group of primary olfactory areas which receive direct input from the olfactory bulb. Orbitofrontal cortices participate in olfactory functions, but the pathways through which they receive olfactory or other input have not been clearly defined. The retrograde tracers horseradish peroxidase and fluorescent dyes were injected in orbital cortices to study their afferent cortical connections. Labeled neurons in primary olfactory areas (prepiriform cortex, anterior olfactory nucleus and olfactory tubercle) were directed mainly to a posterior orbitofrontal region and to a lesser extent the neighboring caudal part of area 13. There was no evidence of direct projections from primary olfactory areas to the rostral parts of area 13, or to areas 12 or 11. Most labeled neurons in primary olfactory areas were directed to agranular cortices, fewer projected to dysgranular areas, and there was no evidence that any reached granular cortices. The areas which received the most robust olfactory projections showed the lowest degree of laminar organization among prefrontal cortices. Early processing in the olfactory system thus takes place in areas which differ sharply on structural grounds from "early" eulaminate post-Rolandic sensory cortices. In addition to olfactory cortical projections, numerous labeled neurons in transitional (limbic) cortices were directed to orbital areas, and fewer but still substantial numbers of afferent neurons were found in eulaminate cortices. Unlike post-Rolandic unimodal sensory areas, which seems to be committed to the processing of input from one sensory modality via sequential and/or parallel pathways, caudal orbital areas received highly distributed input from primary olfactory areas, and in addition, from gustatory, visual, auditory and somatosensory areas. The structural and connectional features of olfactory recipient orbital cortices thus differ markedly from those observed in other sensory association areas and suggest a mode of processing adapted early in cortical evolution.

Animals↗
PubMed1999

Neural encoding in orbitofrontal cortex and basolateral amygdala during olfactory discrimination learning.

Orbitofrontal cortex (OFC) is part of a network of structures involved in adaptive behavior and decision making. Interconnections between OFC and basolateral amygdala (ABL) may be critical for encoding the motivational significance of stimuli used to guide behavior. Indeed, much research indicates that neurons in OFC and ABL fire selectively to cues based on their associative significance. In the current study recordings were made in each region within a behavioral paradigm that allowed comparison of the development of associative encoding over the course of learning. In each recording session, rats were presented with novel odors that were informative about the outcome of making a response and had to learn to withhold a response after sampling an odor that signaled a negative outcome. In some cases, reversal training was performed in the same session as the initial learning. Ninety-six of the 328 neurons recorded in OFC and 60 of the 229 neurons recorded in ABL exhibited selective activity during evaluation of the odor cues after learning had occurred. A substantial proportion of those neurons in ABL developed selective activity very early in training, and many reversed selectivity rapidly after reversal. In contrast, those neurons in OFC rarely exhibited selective activity during odor evaluation before the rats reached the criterion for learning, and far fewer reversed selectivity after reversal. The findings support a model in which ABL encodes the motivational significance of cues and OFC uses this information in the selection and execution of an appropriate behavioral strategy.

Action Potentials↗
PubMed1978

Forebrain projections of the pigeon olfactory bulb.

The olfactory system of the pigeon (Columba livia) was examined. Our electrophysiological and experimental neuroanatomical (Fink-Heimer technique) data showed that axons from the olfactory bulb terminated in both sides of the forebrain. The cortex prepiriformis (olfactory cortex), the hyperstriatum ventrale and the lobus parolfactorius comprised the uncrossed terminal field. The crossed field included the paleostriatum primitivum and the caudal portion of the lobus parolfactorius, areas which were reached through the anterior commissure. In this report the relationships between areas that receive olfactory information and the possible roles that olfaction plays in the birds' behavior are discussed.

Animals↗
PubMed2002

Response of rats to low levels of sarin.

The purpose of this study was to determine whether exposure to levels of sarin causing no overt clinical signs would cause more subtle, adverse health effects that persisted after the exposure ended. Inhalation exposures of male Fischer 344 rats to 0, 0.2, or 0.4 mg/m(3) of sarin for 1 h/day for 1, 5, or 10 days under normal (25 degrees C) and heat-stressed (32 degrees C) conditions were completed and observations were made at 1 day and 1 month after the exposures. The sarin exposures had no observed effects on body weight, respiration rate, and minute volume during exposure nor in body temperature and activity during the 30-day recovery period. There was no evidence of cellular changes in brain determined by routine histopathology nor of any increase in apoptosis. Brain mRNA for interleukin (IL)-1beta, tumor necrosis factor-alpha, and IL-6 was increased in a dose-dependent manner. Autoradiographic studies demonstrated that M1 cholinergic receptor site densities were unchanged at 1 day after repeated exposures with or without heat stress. At 30 days, there was a decrease in M1 receptors in the olfactory tubercle (with and without heat), and, with heat stress, M1 sites also decreased in a dose-dependent manner in the frontal cortex, anterior olfactory nucleus, and hippocampus. M3 receptor sites were not affected by sarin exposure alone. In the presence of heat stress, there was an upregulation in binding site densities in the frontal cortex, olfactory tubercle, anterior nucleus, and striatum immediately after exposure, and these effects persisted at 30 days. Although red blood cell acetylcholinesterase (AChE) was not greatly inhibited by the 1-day exposure, there were 30 and 60% inhibitions after repeated exposures at the low and high doses, respectively. Histochemical staining for AChE demonstrated that sarin exposure alone reduced AChE in the cerebral cortex, striatum, and olfactory bulb. Sarin exposure under heat stress reduced AChE staining in the hippocampus, an area important for memory function. Thus, repeated exposures under heat-stress conditions, to levels of sarin that would not be noticed clinically, resulted in delayed development of brain alterations in cholinergic receptor subtypes that may be associated with memory loss and cognitive dysfunction.

Acetylcholinesterase↗
PubMed1975

An olfactory projection area in orbitofrontal cortex of the monkey.

An olfactory projection area was studied in monkeys anesthetized with Nembutal. 1. Evoked potentials were recorded when the olfactory bulb (OB) was electrically stimulated in the lateroposterior portion of the orbitofrontal cortex (LPOF). However, those potentials disappeared when the anterior pyriform cortex (AP) (probably together with the medial portion of the amygdala (MA)) was aspirated or electrically destroyed. 2. In nearly the entire hypothalamic region, evoked potentials were recorded by the same stimulation of the OB. When the hypothalamic region was stimulated, evoked potentials were recorded in the LPOF. 3. The evoked potentials in the LPOF due to the OB stimulation never disappeared even when the thalamus was extensively aspirated or destroyed electrically, but they did disappear when the anterolateral and dorsoposterior portions of the hypothalamus were absorbed or electrocoagulated. 4. Evoked potentials in the mediodorsal nucleus (MD) of the thalamus were recorded when the OB was stimulated. When this nucleus was stimulated, evoked potentials were observed in the broad extent of the orbitofrontal cortex anterior to the LPOF, but never in the LPOF itself. 5. Monkeys were conditioned to discriminate two odors. When the LPOF was removed, such ability strikingly decreased; but when other areas in the prefrontal cortex were removed, the ability decreased only slightly. 6. It was concluded that there exists an olfactory pathway from the OB to the LPOF through the AP (and probably the MA) and the hypothalamus, but none through the thalamus, and that the LPOF plays an important role in the discrimination of odors. 7. It was proved that the entorhinal cortex (ER) is neither located as an intermediate olfactory area nor is it situated as a higher area than the LPOF in the newly found olfactory pathway stated above. It may be a link between the high olfactory area and the limbic system.

Animals↗