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The actions of pentobarbitone, procaine and tetrodotoxin on synaptic transmission in the olfactory cortex of the guinea-pig.

1 It has been suggested that the depression of excitatory synaptic potentials produced by general anaesthetics can be attributed to a partial blockade of impulse conduction in the terminal branches of axons. This hypothesis has been tested by comparing the actions of pentobarbitone, procaine and tetrodotoxin (TTX) on synaptic transmission in the guinea-pig olfactory cortex. 2 Pentobarbitone (0.1-0.3mM) depressed the evoked synaptic potentials without any significant depression of impulse conduction in the afferent fibres of the lateral olfactory tract (1.o.t). It had no effect on the electrical excitability of either the l.o.t axons or the postsynaptic neurones. 3 Tetrodotoxin (TTX; 1-5x10(-8 M) slowed conduction of impulses in the l.o.t. and decreased the amplitude of the l.o.t compound action potential in proportion to the concentration applied. All concentrations of TTX elevated the electrical threshold of the l.o.t. axons and there was evidence to suggest that the threshold of the postsynaptic neurones was also elevated. The synaptic potentials were depressed in direct proportion to the depression of the l.o.t. compound action potential. 4 Procaine (0.1-0.5 mM) exhibited a pattern of activity intermediate between pentobarbitone and TTX. The most marked effect, seen at all concentrations tested, was a slowing of impulse conduction and a decrease in the electrical excitability of the l.o.t. axons. 5 It is concluded that general anaesthetics (exemplified by pentobarbitone) depress synaptic transmission by interfering with the processes involved in chemical transmission and not by blocking impulse conduction in the terminal branches of afferent nerves.

Animals↗

Antagonists of the NMDA receptor and allopurinol protect the olfactory cortex but not the striatum after intra-cerebral injection of kainic acid.

Overstimulation of the NMDA receptor, as well as generation of excessive amounts of free radicals, has been implicated in excitotoxic brain injuries. We report here that two antagonists of the NMDA receptor and an inhibitor of the free radical-generating enzyme, xanthine oxidase, protect the olfactory cortex but not the striatum after intrastriatal injection of kainic acid. Our results suggest the existence of a precise link between excitotoxic activation of the NMDA receptor and neuropathology related to excessive amounts of free radicals. The focal point of this link may be the entry of Ca2+ through the NMDA receptor and the consequent activation of proteases and free radical-generating systems.

Allopurinol↗

Effects of barbiturates on responses evoked by excitatory amino acids in slices of rat olfactory cortex.

A study has been made of the effects of ranges of concentrations of phenobarbitone, pentobarbitone and thiopentone on responses evoked by gamma-aminobutyric acid (GABA), L-glutamate, L-aspartate, N-methyl-D-aspartate, kainate and quisqualate in slices of olfactory cortex of the rat. All three barbiturates affected GABA-evoked depolarizations similarly in that responses were potentiated by small doses but markedly inhibited at greater concentrations. Responses to L-aspartate and L-glutamate were little affected except at the largest dose of phenobarbitone tested (10 mM). The responses evoked by the selective agonists of excitatory amino acid receptors were inhibited by the barbiturates, the relative sensitivities being quisqualate greater than or equal to N-methyl-D-aspartate greater than or equal to kainate with phenobarbitone, quisqualate greater than or equal to kainate greater than N-methyl-D-aspartate with pentobarbitone and quisqualate greater than kainate = N-methyl-D-aspartate with thiopentone. The possible significance of these findings is discussed.

Amino Acids↗

The laminar distribution of intracortical fibers originating in the olfactory cortex of the rat.

In this study, the autoradiographic method for tracing axonal connections was used to identify the laminar distribution of intracortical fibers originating in the olfactory cortical areas of the rat. Most of the projections can be divided into two major fiber systems with different laminar patterns of termination. The first of these, termed the layer Ib fiber system, arises in the anterior olfactory nucleus, the anterior and posterior piriform cortex, and the lateral entorhinal cortex, and terminates predominantly in layer Ib and, in many cases, layer III of the entire olfactory cortex. The second system, termed the layer II-deep Ib fiber system, originates in three relatively small olfactory cortical areas--the dorsal peduncular cortex, the ventral tenia tecta, and the periamygdaloid cortex--and terminates in and around the cells of layer II in most parts of the olfactory cortex. There is significant overlap in the laminar distribution of the two systems, although the distinction between them is readily apparent. Within the layer Ib fiber system there are relatively slight but consistent differences in the lamination of fibers from different areas. The fibers from the anterior olfactory nucleus are concentrated in the deep part of layer Ib while those from the anterior piriform cortex are concentrated in the superficial part of this layer. The fibers from the posterior piriform cortex tend to be densest in the middle of layer Ib. These differences are maintained in all areas of termination of each set of fibers, both ipsilaterally and contralaterally. In addition, intracortical fibers from the anterior cortical nucleus of the amygdala are distributed throughout layer I, including layer Ia and Ib. Fibers from the nucleus of the lateral olfactory tract terminate bilaterally around the cells of the islands of Calleja and the medial edge of the anterior piriform cortex.

Amygdala↗

A quantitative estimate of the contribution made by various receptor categories to the depolarizations evoked by some excitatory amino acids in the olfactory cortex.

A study has been undertaken to assess the percentage contributions made by N-methyl-D-aspartate (NMDA), kainate and quisqualate receptors to the composite depolarizations evoked by L-cysteate, L-cysteinesulphinate, L-homocysteate and S-sulpho-L-cysteine in the rat olfactory cortex slice. The percentage contribution made by NMDA receptors, which was quantified by measuring the reduction in agonist responses in the presence of the highly selective NMDA receptor antagonist 2-amino-5-phosphonopentanoate (0.1 mM), was: L-homocysteate, 73%; S-sulpho-L-cysteine, 65%; L-cysteate, 42% and L-cysteinesulphinate, 30%. Responses mediated by NMDA, kainate and quisqualate receptors were abolished by a 'desensitization' procedure involving repeated application of a mixture containing high concentrations of the selective agonists followed by perfusion of the non-selective receptor antagonist cis-2,3-piperidine dicarboxylate (5 mM). Following this procedure, responses to L-homocysteate and S-sulpho-L-cysteine were almost abolished and simple calculation gave the contribution of kainate plus quisqualate receptors to the agonist responses as: L-cysteinesulphinate, 46%; L-cysteate, 34%; S-sulpho-L-cysteine, 28% and L-homocysteate, 23%. However, approximately 24% of the composite depolarizations evoked by L-cysteate and L-cysteinesulphinate was mediated by a mechanism not involving NMDA, kainate or quisqualate receptors, neither did it reflect possible electrogenic uptake of the amino acids nor an interaction with 2-amino-4-phosphonobutyrate receptors. It is suggested that this fraction of the depolarizations evoked by L-cysteate and L-cysteinesulphinate might be due to a non-receptor-mediated release of K+ or, perhaps, to activation of an as yet unidentified receptor category.

Amino Acids↗

Decreased excitotoxic sensitivity in the olfactory cortex of adult rats after neonatal NMDA blockade.

Neonatal rats were daily treated with increasing doses of the competitive NMDA antagonist CGP 39551 from postnatal day 1 to 22. At 75-80 days of age the rats were given an excitotoxic dose of kainic acid s.c. Histological examination suggested that the olfactory cortex of the neonatally CGP 39551-treated rats was less damaged than that of controls. This was quantitatively confirmed by assaying the decrease of appropriate neurochemical markers (D-[3H]aspartate uptake and glutamate decarboxylase) as an index of the extent of neuronal degeneration. By contrast, the decrease of the same markers was not different in the hippocampus. These results suggest a selective effect on some brain circuits of adult rats consequent to the neonatal blockade of NMDA receptors and, therefore, add new evidence to a developmental role of this receptor.

2-Amino-5-phosphonovalerate↗

A novel component of cannabis extract potentiates excitatory synaptic transmission in rat olfactory cortex in vitro.

Cannabis is a potential treatment for epilepsy, although the few human studies supporting this use have proved inconclusive. Previously, we showed that a standardized cannabis extract (SCE), isolated Delta9-tetrahydrocannabinol (Delta9-THC), and even Delta9-THC-free SCE inhibited muscarinic agonist-induced epileptiform bursting in rat olfactory cortical brain slices, acting via CB1 receptors. The present work demonstrates that although Delta9-THC (1 microM) significantly depressed evoked depolarizing postsynaptic potentials (PSPs) in rat olfactory cortex neurones, both SCE and Delta9-THC-free SCE significantly potentiated evoked PSPs (all results were fully reversed by the CB1 receptor antagonist SR141716A, 1 microM); interestingly, the potentiation by Delta9-THC-free SCE was greater than that produced by SCE. On comparing the effects of Delta9-THC-free SCE upon evoked PSPs and artificial PSPs (aPSPs; evoked electrotonically following brief intracellular current injection), PSPs were enhanced, whereas aPSPs were unaffected, suggesting that the effect was not due to changes in background input resistance. Similar recordings made using CB1 receptor-deficient knockout mice (CB1-/-) and wild-type littermate controls revealed cannabinoid or extract-induced changes in membrane resistance, cell excitability and synaptic transmission in wild-type mice that were similar to those seen in rat neurones, but no effect on these properties were seen in CB1-/- cells. It appears that the unknown extract constituent(s) effects over-rode the suppressive effects of Delta9-THC on excitatory neurotransmitter release, which may explain some patients' preference for herbal cannabis rather than isolated Delta9-THC (due to attenuation of some of the central Delta9-THC side effects) and possibly account for the rare incidence of seizures in some individuals taking cannabis recreationally.

Animals↗

[Effect of fractions of the cerebrospinal fluid from patients with drug dependence on basic electrophysiological characteristics of the rat olfactory cortex slices].

Heroin addicts at the initial stage of abstinence syndrome were subjected to detoxication by liquorosorption technique. The fractions of their cerebrospinal fluid obtained by the thin layer chromatography technique were analyzed. The substances extracted from the cerebrospinal fluid of drug addicts, presumably peptides, negatively affected the conductive function and synaptic transmission in surviving slices of the olfactory cortex of rats. The conclusion was drawn about a possibility of application of surviving rat brain slices as test object for estimation of the extent of purification of the cerebrospinal fluid from toxic endogenous substances after the liquorosorption.

Adolescent↗

[Modification of redox sites of N-methyl-D-aspartate receptors affects changes in bioelectrical activity of olfactory cortex slices induced by anoxia in rats].

The effects of the thiol oxidative agent 5,5'-dithiobis (2-nitrobenzoic acid) (DTNB) inhibiting NMDA receptors activity on changes of the evoked focal potentials generation (the NMDA and non-NMDA components EPSP) in response to long-term (LA) and short-term (SA) anoxic exposure which induced functional disturbances or promoted increasing of neurons resistance to LA, were studied on the rat olfactory cortex slices (Wistar-Kyoto). It was revealed that DTNB (200 mkM) effectively protected the depression of the EPSP generation induced by LA in the most tested neurons. In addition, DTNB eliminates the protective effect of the SA on focal EPSP generation evoked by LA. Nevertheless this dependence concerns the NMDA component and, to a lesser extent, the non-NMDA component EPSP. A possible role of changes of the NMDA receptor modulatory redox sites in mechanisms of functional disturbances and increasing neuronal resistance induced by hypoxic influences, is discussed.

Animals↗

Odor-driven activity in the olfactory cortex of an in vitro isolated guinea pig whole brain with olfactory epithelium.

We developed a new technique to isolate a whole guinea pig brain with an intact olfactory epithelium (OE) that enables us to access the ventral surface of the brain including olfactory areas with ease during natural odor stimulation. We applied odorants to OE and confirmed that odor-induced local field potentials (LFPs) could be induced in olfactory areas. In the olfactory bulb (OB) and the piriform cortex (PC), odor-induced LFPs consisted of a phasic initial component followed by a fast activity oscillation in the beta range (20 Hz). To understand the neural mechanisms of odor-induced responses especially in the anterior PC, we analyzed odor-induced LFPs, together with unit activity data. We confirmed that the initial component of odor-induced response has a characteristic temporal pattern, generated by a relatively weak direct afferent input, followed by an intra-cortical associative response, which was associated with a phasic inhibition. The beta oscillation might be formed by the repetition of these network activities. These electrophysiological data were consistent with the results of previous studies that used slice or in vivo preparations, suggesting that the olfactory neural network and activities of the brain are preserved in our new in vitro preparation. This study provides the basis for clarifying the sequence of neural activities underlying odor information processing in the brain in vitro following natural olfactory stimulation.

Action Potentials↗

Multi-gradient echo with susceptibility inhomogeneity compensation (MGESIC): demonstration of fMRI in the olfactory cortex at 3.0 T.

Short image acquisition times and sensitivity to magnetic susceptibility favor the use of gradient echo imaging methods in functional MRI (fMRI). However, magnetic susceptibility effects attributed to air-tissue interfaces also lead to severe signal loss in images of the large inferior frontal and lateral temporal cortices of the human brain, which renders these regions inaccessible to fMRI. The signal loss is caused by the local field gradients in the silce selection direction. A multigradient echo with magnetic susceptibility inhomogeneity compensation method (MGESIC) is proposed to overcome this problem. The MGESIC method effectively corrects the susceptibility artifacts and maintains the advantages of gradient echo methods to both BOLD sensitivity and fast image acquisition. The effectiveness of the MGESIC method is demonstrated by fMRI experimental results within the olfactory cortex.

Humans↗

Remembrance of odors past: human olfactory cortex in cross-modal recognition memory.

Episodic memory is often imbued with multisensory richness, such that the recall of an event can be endowed with the sights, sounds, and smells of its prior occurrence. While hippocampus and related medial temporal structures are implicated in episodic memory retrieval, the participation of sensory-specific cortex in representing the qualities of an episode is less well established. We combined functional magnetic resonance imaging (fMRI) with a cross-modal paradigm, where objects were presented with odors during memory encoding. We then examined the effect of odor context on neural responses at retrieval when these same objects were presented alone. Primary olfactory (piriform) cortex, as well as anterior hippocampus, was activated during the successful retrieval of old (compared to new) objects. Our findings indicate that sensory features of the original engram are preserved in unimodal olfactory cortex. We suggest that reactivation of memory traces distributed across modality-specific brain areas underpins the sensory qualities of episodic memories.

Adolescent↗

Afferent and association fiber differences in short-term potentiation in piriform (olfactory) cortex of the rat.

1. The effects of low-frequency stimulus trains on synaptically evoked responses in piriform cortex pyramidal cells were studied by the use of intracellular recording techniques in an in vitro slice preparation. Afferent and association fiber systems were differentially stimulated with electrodes placed in layer 1a or layer 1b, respectively. To quantify synapse modifiability, the heights of postsynaptic potentials (PSPs) elicited by paired-pulse stimulation (100-ms interval) were averaged over a 50-s period before and after a set of 10 stimulus trains (10 pulses each, 20 Hz, 5-s interpulse interval). 2. Afferent and association fibers showed consistent differences in their response to stimulation during the period lasting from approximately 10 to 200 s after presentation of trains. During this time period, the responses to stimulation of association fibers in layer 1b displayed a short-term potentiation, which over the 10 posttrain trials, produced an average increase in PSP height of 23.2 +/- 3.7% (mean +/- SE). On the other hand, responses to layer 1a stimulation showed an average depression of 10.9 +/- 3.6%. Layer 1b potentiation decayed with time constant roughly estimated at 79 s. Layer 1b potentiation appeared even at very low stimulus voltages and after local association fiber input had been cut, suggesting that it was largely a monosynaptic effect. 3. In the period immediately after train presentations, responses evoked by both layers showed a short-term augmentation with a time constant around 3 s. In layer 1a, this augmentation was superimposed on a depression with slow recovery. At longer times after train presentation (greater than 5 min), 2 cells out of 46 showed changes (increases) in synaptic efficacy in response to layer 1b stimulation. 4. In the current experiments both layers 1a and 1b showed statistically significant facilitation before the presentation of stimulus trains. However, layer 1b facilitation decreased from 22.7 +/- 3.5% to a statistically insignificant 3.9 +/- 3.3% after the presentation of trains, whereas layer 1a facilitation remained at a statistically significant level of 23.1 +/- 5.7%. 5. These experiments show that pyramidal cell responses to stimulation of the afferent and association fiber systems are affected differently by the previous presentation of trains of stimuli. This suggests that mechanisms of synaptic modification may differ between the afferent and intrinsic association synaptic projections onto single pyramidal cells in olfactory cortex.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

New features of connectivity in piriform cortex visualized by intracellular injection of pyramidal cells suggest that "primary" olfactory cortex functions like "association" cortex in other sensory systems.

Associational connections of pyramidal cells in rat posterior piriform cortex were studied by direct visualization of axons stained by intracellular injection in vivo. The results revealed that individual cells have widespread axonal arbors that extend over nearly the full length of the cerebral hemisphere. Within piriform cortex these arbors are highly distributed with no regularly arranged patchy concentrations like those associated with the columnar organization in other primary sensory areas (i.e., where periodically arranged sets of cells have common response properties, inputs, and outputs). A lack of columnar organization was also indicated by a marked disparity in the intrinsic projection patterns of neighboring injected cells. Analysis of axonal branching patterns, bouton distributions, and dendritic arbors suggested that each pyramidal cell makes a small number of synaptic contacts on a large number (>1000) of other cells in piriform cortex at disparate locations. Axons from individual pyramidal cells also arborize extensively within many neighboring cortical areas, most of which send strong projections back to piriform cortex. These include areas involved in high-order functions in prefrontal, amygdaloid, entorhinal, and perirhinal cortex, to which there are few projections from other primary sensory areas. Our results suggest that piriform cortex performs correlative functions analogous to those in association areas of neocortex rather than those typical of primary sensory areas with which it has been traditionally classed. Findings from other studies suggest that the olfactory bulb subserves functions performed by primary areas in other sensory systems.

Animals↗

Time course of interictal EEG patterns induced by a penicillin injection into the olfactory cortex.

In awake rats, the time courses of behavioural and cortical interictal hyperactivity patterns were investigated following an injection of the GABA antagonist Na-penicillin (PCN) (125 IU/0.5 microliters) into the olfactory or motor cortex. The cortical EEG was recorded by means of 6 AgAgCl-electrodes, behaviour was videotaped simultaneously. Behavioural hyperactivity developed immediately after PCN injection. It lasted longer than 2.5 to 4 h in the olfactory but less than 30 min in the motor cortex group of rats. The interictal EEG pattern of the olfactory group was characterized by a slow establishing of three centers of high cortical activity. They were located in the ipsilateral central and the contralateral frontal and occipital cortex. In the motor cortex group, however, a cortical center of high activity developed immediately after the PCN injection near the injection site only, or additionally, over the homotopic area of the contralateral hemisphere. The results indicate different susceptibility properties in the underlying neuronal networks. Ongoing epileptiform activity obviously modifies this susceptibility in a site-specific manner. Moreover, the time-correlated occurrence of high activity in the frontal motor and occipital cortex evoked by a PCN injection into the olfactory cortex suggests a close coupling of these three areas. A coupling between the frontal motor, occipital and focal area could not be shown, if PCN was injected into the motor cortex.

Animals↗

Ketamine-xylazine-induced slow (< 1.5 Hz) oscillations in the rat piriform (olfactory) cortex are functionally correlated with respiration.

The occurrence of low frequency (<1.5 Hz) cerebral cortical oscillations during slow-wave sleep has recently lead to the suggestion that this pattern of activity is specifically associated with conditions in which the brain is mostly closed to external inputs and running on its own. In the current experiments, we used a combination of in vivo intracellular and extracellular field potential recordings obtained under conditions of ketamine-xylazine anesthesia to examine slow-wave behavior in the olfactory system. We demonstrate the occurrence of low-frequency oscillations in field potentials of both the olfactory bulb and cortex and in the membrane potentials of cortical pyramidal cells. By monitoring ongoing breathing, we also show that these oscillations are all correlated with the natural breathing cycle. Using a tracheotomized preparation, we demonstrate that slow oscillatory patterns could occasionally be produced even when air is no longer entering the nose, supporting the view that the olfactory system has an intrinsic propensity to oscillate. However, in the case of tracheotomized rats, the amplitude and regularity of the oscillations as well as their patterns of correlation are disrupted. All temporal relationships were restored when air was pulsed into the nostrils. We conclude that, in the olfactory system of freely breathing rats, there is a strong relationship between the occurrence and timing of slow oscillations and the ongoing periodic sensory input resulting from respiration. This coupling between olfactory cortex slow oscillations and respiration may result from the interaction between respiratory-related rhythmic input and the tendency for olfactory structures to oscillate intrinsically. We believe this finding has important functional as well as evolutionary implications.

Animals↗

Fetal olfactory bulb transplants send projections to host olfactory cortex in the rat.

We are using the rat olfactory system to study developmental details of neurotransplantation. Tritiated [3H]thymidine-labeled fetal olfactory bulbs (OBs), were transplanted immediately into sites from which the neonatal host OB was removed. Subsequently, a small lesion was placed in the region of the transplanted OB and the tissue studied, using degeneration methods and autoradiography. Only OB's with extensive [3H]-label and precise lesions confined to the labeled areas were used. Degeneration was found mainly in the ipsilateral piriform cortex with lesser amounts at other nearby sites. The results demonstrate successfully transplanted donor OBs that send axons to specific and appropriate target areas of the host brain.

Animals↗