Olfactory Cortical Neurons Research Articles

Lack of correlation between odor composition and neuron response in the olfactory cortex of mice

In the mammalian brain, sensory circuits are usually organized in a topographical way, meaning that, for a given brain region, neighboring neurons respond to stimuli close to each other in their sensory space. Olfaction is a notable exception to this rule; projections to the olfactory system are sparse and dispersed, leading to no apparent topography. Here, we assessed the presence of a topographical map in the mouse olfactory cortex, using a previously generated online dataset of neuronal recordings. The dataset consisted of about 1,800 olfactory cortical neurons collected from 10 mice, stimulated with a panel of 15 odorants. If there is no odor topography in the olfactory cortex, there should be no correlation between the chemical composition of odorants and their evoked neuronal response. To test this hypothesis, we first calculated odor similarity between each pair of odorants, using their chemical traits. Then, for each odor pair, we computed the similarity between their evoked neuronal responses. Finally, we assessed the relationship between odor similarity and neuronal response similarity. We found little to no correlation between the two variables (R2 averaged across all mice tested: 0.015), which suggests the lack of topography in the murine olfactory cortex and opens new questions into what other variables might play a role in odorant distinction.

The Nose-To-Brain Transport of Polymeric Nanoparticles Is Mediated by Immune Sentinels and Not by Olfactory Sensory Neurons.

The nose-to-brain (N-to-B) transport mechanism of nanoparticles through the olfactory epithelium (OE) is not fully understood. Most research utilized nasal epithelial cell models completely deprived of olfactory cells. Aiming to shed light into key cellular pathways, in this work, for the first time, the interaction of polymeric nanoparticles in a 17-483 nm size range and with neutral and negatively and positively charged surfaces with primary olfactory sensory neurons, cortical neurons, and microglia isolated from olfactory bulb (OB), OE, and cortex of newborn rats is investigated. After demonstrating the good cell compatibility of the different nanoparticles, the nanoparticle uptake by confocal laser scanning fluorescence microscopy is monitored. Our findings reveal that neither olfactory nor forebrain neurons internalize nanoparticles. Conversely, it is demonstrated that olfactory and cortical microglia phagocytose the nanoparticles independently of their features. Overall, our findings represent the first unambiguous evidence of the possible involvement of microglia in N-to-B nanoparticle transport and the unlikely involvement of neurons. Furthermore, this approach emerges as a completely new experimental tool to screen the biocompatibility, uptake, and transport of nanomaterials by key cellular players of the N-to-B pathway in nanosafety and nanotoxicology and nanomedicine.

Sharp wave-associated activity patterns of cortical neurons in the mouse piriform cortex.

The olfactory piriform cortex (PC) is thought to participate in olfactory associative memory. Like the hippocampus, which is essential for episodic memory, it belongs to an evolutionally conserved paleocortex and comprises a three-layered cortical structure. During slow-wave sleep, the olfactory PC becomes less responsive to external odor stimuli and instead displays sharp wave (SPW) activity similar to that observed in the hippocampus. Neural activity patterns during hippocampal SPW have been intensively studied in terms of memory consolidation; however, little is known about the activity patterns of olfactory cortical neurons during olfactory cortex sharp waves (OC-SPWs). In this study, we recorded multi-unit neural activities in the anterior PC in urethane-anesthetized mice. We found that the activity patterns of olfactory cortical neurons during OC-SPWs were non-randomly organized. Individual olfactory cortical neurons varied in the timings of their peak firing rates during OC-SPW events. Moreover, specific pairs of olfactory cortical neurons were more frequently activated together than expected by chance. On the basis of these observations, we speculate that coordinated activation of specific subsets of olfactory cortical neurons repeats during OC-SPWs, thereby facilitating synaptic plasticity underlying the consolidation of olfactory associative memories.

Slow-Wave Sleep-Imposed Replay Modulates Both Strength and Precision of Memory

Odor perception is hypothesized to be an experience-dependent process involving the encoding of odor objects by distributed olfactory cortical ensembles. Olfactory cortical neurons coactivated by a specific pattern of odorant evoked input become linked through association fiber synaptic plasticity, creating a template of the familiar odor. In this way, experience and memory play an important role in odor perception and discrimination. In other systems, memory consolidation occurs partially via slow-wave sleep (SWS)-dependent replay of activity patterns originally evoked during waking. SWS is ideal for replay given hyporesponsive sensory systems, and thus reduced interference. Here, using artificial patterns of olfactory bulb stimulation in a fear conditioning procedure in the rat, we tested the effects of imposed post-training replay during SWS and waking on strength and precision of pattern memory. The results show that imposed replay during post-training SWS enhanced the subsequent strength of memory, whereas the identical replay during waking induced extinction. The magnitude of this enhancement was dependent on the timing of imposed replay relative to cortical sharp-waves. Imposed SWS replay of stimuli, which differed from the conditioned stimulus, did not affect conditioned stimulus memory strength but induced generalization of the fear memory to novel artificial patterns. Finally, post-training disruption of piriform cortex intracortical association fiber synapses, hypothesized to be critical for experience-dependent odor coding, also impaired subsequent memory precision but not strength. These results suggest that SWS replay in the olfactory cortex enhances memory consolidation, and that memory precision is dependent on the fidelity of that replay.

Olfactory cortical neurons read out a relative time code in the olfactory bulb

Odor stimulation evokes complex spatiotemporal activity in the olfactory bulb, suggesting that the identity of activated neurons as well as the timing of their activity convey information about odors. However, whether and how downstream neurons decipher these temporal patterns remains debated. We addressed this question by measuring the spiking activity of downstream neurons while optogenetically stimulating two foci in the olfactory bulb with varying relative timing in mice. We found that the overall spike rates of piriform cortex neurons were sensitive to the relative timing of activation. Posterior piriform cortex neurons showed higher sensitivity to relative input times than neurons in the anterior piriform cortex. In contrast, olfactory bulb neurons rarely showed such sensitivity. Thus, the brain can transform a relative time code in the periphery into a firing-rate-based representation in central brain areas, providing evidence for the relevance of relative time-based code in the olfactory bulb.

Fast and dynamic odor encoding in rat olfactory cortex during odor discrimination task

Event Abstract Back to Event Fast and dynamic odor encoding in rat olfactory cortex during odor discrimination task Active movement of sensory organs plays an important role in many sensory modalities. In olfaction, animals sniffing frequency shifts dynamically depending on animals? behavioral states or task demands. Previous behavioral studies from our group showed that rats can achieve highly accurate odor discrimination with a single sniff, suggesting that sniffing is a unit of odor encoding (Uchida and Mainen, 2003). However, very little is known about how active sniffing affects odor encoding by neurons, because most neurophysiological studies in mammalian olfaction have been performed in anesthetized animals. In this study, we wished to address how odor representations develop over sniff cycles and how these representations relate to behavioral performance. We focused on the olfactory cortex because it is closer to behavioral output than the olfactory bulb and therefore we expected that it may be easier to establish direct links between behavioral performance and neuronal activity. We recorded neural activity from individual cells in the anterior piriform cortex of rats using a multi-electrode recording technique while they performed a two-alternative odor discrimination task. The rats were trained to sample an odor at a central odor port and to go left or right to a choice port to obtain water rewards. In each session, at least six odors were used, with half of them assigned to either the left or right reward port. Simultaneously, respiration was monitored using a temperature sensor implanted in the nostril. Olfactory cortical neurons showed robust and transient odor responses with specific latencies that were tightly locked to sniff cycles. Many neurons showed odor-specific adaptation or facilitation at the second sniff. We then examined how the ensemble activity evolved across sniffs. Using principal component analysis, it could be seen that ensemble activity followed odor specific trajectories. Interestingly, the ensemble activity in the first sniff was significantly different from that in the second sniff. This contrasts with the highly similar trajectories repeated over multiple sniff cycles in previous studies in anesthetized animals. We next quantified information content within each sniff cycle by asking how well an ideal observer can discriminate six odors based on the neural activity. To do this we used several different pattern classification methods including support vector machines. This analysis showed that the discriminability of odors developed very rapidly within the first sniff and that the second sniff provided less information. Using the combined spikes during the first and second sniffs did not improve odor discriminability significantly compared to using only spike during the first sniff. In summary, an informative odor representation in the olfactory cortex of behaving rats appears to develop very rapidly within a single sniff and is not substantially augmented odor representation in the second sniff. These observations may help to explain the behavioral observation that multiple sniffs in the odor sampling port does not result in increased discrimination performance. This study suggests that olfactory processing during active sniffing favors rapid processing over prolonged temporal integration during an odor discrimination task.

Cell expression of GDAP1 in the nervous system and pathogenesis of Charcot‐Marie‐Tooth type 4A disease

Mutations in the mitochondrial protein GDAP1 are the cause of Charcot-Marie-Tooth type 4A disease (CMT4A), a severe form of peripheral neuropathy associated with either demyelinating, axonal or intermediate pheno-types. GDAP1 is located in the outer mitochondrial membrane and it seems that may be related with the mitochondrial network dynamics. We are interested to define cell expression in the nervous system and the effect of mutations in mitochondrial morphology and pathogenesis of the disease. We investigated GDAP1 expression in the nervous system and dorsal root ganglia (DRG) neuron cultures. GDAP1 is expressed in motor and sensory neurons of the spinal cord and other large neurons such as cerebellar Purkinje neurons, hippocampal pyramidal neurons, mitral neurons of the olfactory bulb and cortical pyramidal neurons. The lack of GDAP1 staining in the white matter and nerve roots suggested that glial cells do not express GDAP1. In DRG cultures satellite cells and Schwann cells were GDAP1-negative. Overexpression of GDAP1-induced fragmentation of mitochondria suggesting a role of GDAP1 in the fission pathway of the mitochondrial dynamics. Missense mutations showed two different patterns: most of them induced mitochondrial fragmentation but the T157P mutation showed an aggregation pattern. Whereas null mutations of GDAP1 should be associated with loss of function of the protein, missense mutations may act through different pathogenic mechanisms including a dominant-negative effect, suggesting that different molecular mechanisms may underlay the pathogenesis of CMT4A.

Cholinergic neurons of the adult rat striatum are immunoreactive for glutamatergic N-methyl- d-aspartate 2D but not N-methyl- d-aspartate 2C receptor subunits

Cholinergic neurons of the striatum play a crucial role in controlling output from this region. Their firing is under the control of a relatively limited glutamatergic input, deriving principally from the thalamus. Glutamate transmission is effected via three major subtypes of receptors, including those with affinity for N-methyl- d-aspartate (NMDA) and the properties of individual receptors reflect their precise subunit composition. We examined the distribution of NMDA2C and NMDA2D subunits in the rat striatum using immunocytochemistry and show that a population of large neurons is strongly immunoreactive for NMDA2D subunits. From their morphology and ultrastructure, these neurons were presumed to be cholinergic and this was confirmed with double immunofluorescence. We also show that NMDA2C is present in a small number of septal and olfactory cortical neurons but absent from the striatum. Receptors that include NMDA2D subunits are relatively insensitive to magnesium ion block making neurons more likely to fire at more negative membrane potentials. Their localization to cholinergic neurons may enable very precise regulation of firing of these neurons by relatively small glutamatergic inputs.

Mixing Scents

How are odors represented in the higher processing areas of the brain? Zou and Buck compared the responses of mouse olfactory cortical neurons to binary mixtures of odorants versus their individual components. They monitored neuronal activity in the anterior piriform cortex of the same animals in response to individual odors and mixtures. The technique used enabled the authors to monitor neuronal activity in response to two temporally segregated experiences. The results suggest that olfactory cortical neurons receive convergent input from multiple odorant receptors and that a subpopulation may require such convergent input for activation. Z. Zou, L. B. Buck, Combinatorial effects of odorant mixes in olfactory cortex. Science 311 , 1477-1481 (2006). [Abstract] [Full Text]

Evidence for the involvement of G-proteins in the generation of the slow poststimulus afterdepolarisation (sADP) induced by muscarinic receptor activation in rat olfactory cortical neurones in vitro

The involvement of G-proteins in generating the slow poststimulus afterdepolarising potential (sADP) induced by muscarinic receptor activation in immature (P10–20) rat olfactory cortical brain slice neurones was investigated under whole-cell patch clamp, using GTP-γ-S (G-protein activator) or GDP-β-S (G-protein blocker)-filled electrodes. In control experiments using K methylsulphate electrodes, cell resting potential ( V m) and spike firing properties were unaffected over 10–15 min recording, although input resistance ( R N) was slightly increased (∼14%). Oxotremorine-M (OXO-M; 10 μM) produced a reversible slow depolarisation, an increase in R N (∼90%) and induction of a slow poststimulus inward tail current ( I ADP) (measured under voltage clamp at −60 mV) that was sustained during drug exposure (up to 15 min); the amplitude of slow inward rectifier ( I h) currents activated from −50 mV were also apparently increased. By contrast, in GTP-γ-S-loaded cells, R N was consistently decreased (∼22%) and spike firing threshold ( V th) was raised (∼5 mV) after 10 min recording. In ∼60% of loaded cells, a persistent muscarinic slow inward current and I ADP were induced by OXO-M; I h relaxation amplitude was also significantly decreased. The effects of GTP-γ-S on R N, V th and I h were partly counteracted by adding Ba 2+ (100 μM) to the bathing medium or mimicked by adding baclofen (GABA B receptor agonist; 100 μM) to normally-recorded cells. Intracellular GDP-β-S (up to 30 min) had no effect on cell membrane properties or I h, but irreversibly blocked the muscarinic slow inward current and I ADP induced by OXO-M. We conclude that both muscarinic responses require G-protein-linked transduction mechanisms for their generation.

Proceedings of a Symposium on Cortical Information Processing in the Olfactory System held at the 22nd Annual Meeting of the Association for Chemoreception Sciences (AChemS) on April 28, 2000, in Sarasota, Florida

Higher order sensory processes such as perception, memory and emotion are generally ascribed to activity within the cerebral hemispheres. In most sensory systems, cortical processing is believed to be required for the extraction, discrimination and identification of complex features, binding of those features into perceptual wholes, and memory of those perceptions and their associated emotional consequences or context. In parallel with the rapid growth of our understanding of olfactory transduction and peripheral odor coding over the past decade, there has been a marked increase in our understanding of how that peripheral coding is enhanced and embellished within olfactory cortical areas. Accordingly, a symposium was held during the 22nd annual meeting of AChemS, where four speakers discussed the role and mechanisms of cortical information processing in the olfactory system. The talks included a discussion of how detailed analyses of cortical anatomy and physiology can lead to specific, testable predictions of cortical function (Lewis Haberly), a description of receptive fields of olfactory cortical neurons and direct comparison with those of cortical afferents, mitral/tufted cells of the olfactory bulb (Donald Wilson), a description of how behaviorally responsive neuromodulatory inputs such as norepinephrine and acetylcholine can shape olfactory cortical functions important for odor recognition and memory (Michael Hasselmo), and how the cortex associates tastes and odors for flavor representation and remembers hedonic associations of those flavors (Edmund Rolls). The resulting series of manuscripts compiled here represent our current understanding of cortical mechanisms in olfactory sensory processing, and hopefully will encourage future work on the role of the cortex as an important mediator of olfactory sensations, perceptions and memories. This symposium was sponsored by a grant from the National Institutes of Deafness and Communication Disorders (DC02038).

Investigation of the role of intracellular Ca(2+) stores in generation of the muscarinic agonist-induced slow afterdepolarization (sADP) in guinea-pig olfactory cortical neurones in vitro.

1. Intracellular recordings were made from guinea-pig olfactory cortical brain slice neurones to assess the possible role of intracellular Ca(2+) stores in the generation of the slow post-stimulus afterdepolarization (sADP) and its underlying tail current (I(ADP)), induced by muscarinic receptor activation. 2. Caffeine or theophylline (0.5 - 3 mM) reduced the amplitude of the I(ADP) (measured under 'hybrid' voltage clamp) induced in the presence of the muscarinic agonist oxotremorine-M (OXO-M, 10 microM) by up to 96%, without affecting membrane properties or muscarinic depolarization of these neurones. 3. The L-type Ca(2+) channel blocker nifedipine (1, 10 microM) also inhibited I(ADP) (by up to 46%), while ryanodine (10 microM) (a blocker of Ca(2+) release from internal stores) produced a small ( approximately 10%) reduction in I(ADP) amplitude; however, neither 10 microM dantrolene (another internal Ca(2+) release blocker) nor the intracellular Ca(2+) store re-uptake inhibitors thapsigargin (3 microM) or cyclopiazonic acid (CPA, 15 microM) affected I(ADP) amplitude. 4. IBMX (100 microM), a phosphodiesterase inhibitor, also had no effect on I(ADP). Furthermore, inhibition of I(ADP) by caffeine was not reversed by co-application of 100 microM adenosine. 5. Caffeine (3 mM) or nifedipine (10 microM) reduced the duration of presumed Ca(2+) spikes revealed by intracellular Cs(+) loading. When applied in combination, nifedipine and caffeine effects were occlusive, rather than additive, suggesting a common site of action on L-type calcium channels. 6. We conclude that Ca(2+)-induced Ca(2+) release (CICR) from internal stores does not contribute significantly to muscarinic I(ADP) generation in olfactory cortical neurones. However caffeine and theophylline, which enhance CICR in other systems, blocked I(ADP) induction. We suggest that this action might involve a combination of L-type voltage-gated Ca(2+) channel blockade, and a direct inhibitory action on the putative I(ADP) K(+) conductance.

Muscarinic agonist-induced burst firing in immature rat olfactory cortex neurons In vitro.

Age-related changes in pre-/postsynaptic muscarinic (mAChR) and metabotropic-glutamate (mGluR) responsiveness were studied in slices of olfactory cortex from both immature [postnatal day 16-22 (P16-P22)] and adult (>/=P40) rats, using a conventional intracellular recording technique. In adult neurons, bath application of the mAChR agonist oxotremorine-M (OXO-M; 10 microM), or the selective mGluR agonist 1-aminocyclopentane-1S-3R-dicarboxylic acid (1S,3R-ACPD; 10 microM) evoked sustained membrane depolarizations, increases in input resistance, intense repetitive firing, and the appearance of a slow poststimulus afterdepolarizing potential (sADP). Excitatory postsynaptic potentials (EPSPs) evoked by local electrical stimulation of association fiber terminals were also depressed. In contrast, in neurons from immature slices, the 10 microM OXO-M-induced membrane depolarization was followed by the appearance of spontaneous rhythmic epileptiform activity, which was voltage independent and reversible on drug wash out. Epileptiform bursts were abolished or reduced by coapplication of tetrodotoxin (1 microM), atropine (1 microM), pirenzepine (100-200 nM), the N-methyl-D-aspartate (NMDA) receptor antagonist -amino-5-phosphonovaleric acid (-APV; 100 microM), the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 5-20 microM), the anesthetic-sedative barbiturate pentobarbitone (100 microM), or by raising the extracellular Mg2+ concentration, whereas a clear facilitatory effect was exhibited by the selective gamma-aminobutyric acid-A (GABAA) receptor blocker (-)-bicuculline methiodide (10 microM). The epileptogenic effects induced by OXO-M were indistinguishable from those produced by 4-aminopyridine (4-AP; 100-200 microM), although these latter actions were unaffected by atropine. In slices from immature animals, electrical stimulation of layer III association fibers in the presence of 10 microM OXO-M was accompanied by a dramatic prolongation of evoked depolarizing postsynaptic potentials (PSPs), with the appearance of recurrent superimposed spike discharges. This effect was readily reversed on wash out of OXO-M. No comparable age-dependent differences were observed in the nature or time course of 1S,3R-ACPD-evoked pre- (or post)synaptic responses, even in immature cells where muscarinic epileptiform activity had previously been demonstrated. We suggest that the overall susceptibility toward muscarinic-induced epileptiform discharge in immature olfactory cortical neurons may depend on the functional integrity of presynaptic inhibitory mAChRs; additional contributing mechanisms were also considered.

1-Aryl-3,5-dihydro-4H-2,3-benzodiazepin-4-ones: Novel AMPA Receptor Antagonists

Our previous publication (Eur. J. Pharmacol. 1995, 294, 411-422) reported preliminary chemical and biological studies of some 2,3-benzodiazepines, analogues of 1-(4-aminophenyl)-4-methyl-7,8-(methylenedioxy)-5H-2,3-benzodiazepine (1, GYKI 52466), which have been shown to possess significant anticonvulsant activity. This paper describes the synthesis of new 1-aryl-3,5-dihydro-4H-2,3-benzodiazepin-4-ones and the evaluation of their anticonvulsant effects. The observed findings extend the structure-activity relationships previously suggested for this class of anticonvulsants. The seizures were evoked both by means of auditory stimulation in DBA/2 mice and by pentylenetetrazole or maximal electroshock in Swiss mice. 1-(4'-Aminophenyl)- (38) and 1-(3'-aminophenyl)-3,5-dihydro-7,8-dimethoxy-4H-2,3-benzodiazepin- 4-one (39), the most active compounds of the series, proved to be more potent than 1 in all tests employed. In particular, the ED50 values against tonus evoked by auditory stimulation were 12.6 micromol/kg for derivative 38, 18.3 micromol/kg for 39, and 25.3 micromol/kg for 1. Higher doses were necessary to block tonic extension induced both by maximal electroshock and by pentylenetetrazole. In addition these compounds exhibited anticonvulsant properties that were longer lasting than those of compound 1 and were less toxic. The novel 2,3-benzodiazepines were also investigated for a possible correlation between their anticonvulsant activities against convulsions induced by 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) and their affinities for benzodiazepine receptors (BZR). The 2,3-benzodiazepines did not affect the binding of [3H]flumazenil to BZR, and conversely, their anticonvulsant effects were not reversed by flumazenil. On the other hand the 2,3-benzodiazepines antagonized seizures induced by AMPA and aniracetam in agreement with an involvement of the AMPA receptor. In addition, both the derivative 38 and the compound 1 markedly reduced the AMPA receptor-mediated membrane currents in guinea-pig olfactory cortical neurons in vitro in a noncompetitive manner. The derivatives 25 and 38-40 failed to displace specific ligands from N-methyl-D-aspartate (NMDA), AMPA/kainate, or metabotropic glutamate receptors.

Metabotropic glutamate receptor subtypes mediating slow inward tail current (IADP) induction and inhibition of synaptic transmission in olfactory cortical neurones

1. The pharmacological features of the pre- and postsynaptic metabotropic glutamate receptors (mGluRs) present in the guinea-pig olfactory cortex, were examined in brain slices in vitro by use of a conventional intracellular current clamp/voltage clamp recording technique. 2. Bath-application of trans-aminocyclopentane-1,3-dicarboxylic acid (trans-ACPD) (50 microM) produced a sustained membrane depolarization, increase in cell excitability and induction of a post-stimulus inward (after depolarizing) tail current (IADP) (measured under 'hybrid' voltage clamp) similar to those evoked by the muscarinic receptor agonist oxotremorine-M (OXO-M, 2 microM). 3. L-Glutamate (0.25 1 mM. in the presence of 20 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 100 microM-DL-amino-5-phosphono valeric acid (DL-APV)) or the broad spectrum mGluR agonists 1S,3R-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD, 10 microM), 1S,3S-ACPD (50 microM), ibotenate (Ibo; 25 microM. in the presence of 100 microM DL-APV), the selective mGluR I agonists (S)-3,5-dihydroxyphenylglycine ((S)-3,5-DHPG, 10 microM), (S)-3-hydroxyphenylglycine ((S)-3HPG, 50 microM), or quisqualate (10 microM, in the presence of 20 microM CNQX), but not the mGluR II agonist 2S,1'S,2'S-2-(2'-carboxycyclopropyl)-glycine (L-CCG1,1 microM) or mGluR III agonist L(+)-2-amino-4-phosphonobutyric acid (L-AP4, 1 mM), were all effective in producing membrane depolarization and inducing a post-stimulus IADP. Unexpectedly, the proposed mGluR II-selective agonist (2S,1'R,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)-glycine (DCG-IV, 10 microM, in the presence of 100 microM DL-APV) was also active. 4. The excitatory effects induced by 10 microM 1S,3R-ACPD were reversibly antagonized by the mGluR I/II antagonist (1)-alpha-methyl-4-carboxyphenylglycine ((+)-MCPG, 0.5 1 mM), as well as the selective mGluR I antagonists (S)-4-carboxyphenylglycine ((S)-4CPG) and (S)-4-carboxy-3-hydroxyphenyl glycine ((S)-4C3HPG) (both at 1 mM), but not the nonselective mGluR antagonist L(+)-2-amino-3-phosphonopropionic acid (L-AP3, 1 mM) or the selective mGluR III antagonist (S)-alpha-methyl-L-AP4 (MAP4, 1 mM). 5. The excitatory postsynaptic potentials (e.p.s.ps), induced by single focal stimulation of cortical excitatory fibre tracts, were markedly reduced by 1S,3R-ACPD or L-AP4 (both at 10 microM), and by the selective mGluR II agonists (mGluR 1 antagonists) (S)-4CPG or (S)-4C3HPG (both at 1 mM) but not (S)-3,5-DHPG or (S)-3HPG (both at 100 microM). 6. The inhibitory effects of 1S-3R-ACPD, but not L-AP4, were reversibly blocked by (+)-MCPG (1 mM), whereas those produced by L-AP4, but not 1S,3R-ACPD, were blocked by the selective mGluR III antagonist MAP4 (1 mM). 7. It is concluded that a group I mGluR is most likely involved in mediating excitatory postsynaptic effects, whereas two distinct mGluRs (e.g. group II and III) might serve as presynaptic inhibitory autoreceptors in the guinea-pig olfactory cortex.

Odor coding properties of frog olfactory cortical neurons

Until now, in amphibians, response odor properties of primary cortical neurons had never been investigated. Furthermore, very few data on this subject are available in other species. This prompted us to explore the functional properties of olfactory cortical neurons at rest and in response to odors. To achieve this, our experience with odor coding in the first two stages of the frog olfactory system, the olfactory mucosa and the olfactory bulb, led us to use odor stimuli which were chemical compounds with known stimulating properties, delivered to the mucosa in controlled conditions over a wide concentration range. Most of the cortical neurons were found to be very silent at rest, their average spontaneous activity being significantly lower than that of bulb neurons recorded previously in the same conditions. Cortical cells displayed, with all odors combined, 35% excitatory responses and 8% inhibitory responses. The excitatory response rate was similar to that of the bulb, while the inhibitory response rate was about 4.5-fold lower. Interestingly, two functional groups of cortical cells emerged based both on differences in response temporal patterning to odors delivered at increasing concentrations and in qualitative discrimination power. Regarding intensity coding, group 1 cells (53%) displayed “classical” temporal pattern evolution, increase of discharge frequencies and decrease of latency and burst duration, over the concentration range. The responses of group 2 cells (47%) were clearly original, since they consisted of a single spike (or more rarely two spikes) occurring with a strictly reproducible latency at a given concentration and a decreased latency as a function of increasing concentration. The dynamics of cell recruitment in the cortex showed that group 1 cell recruitment mimicked that of mitral cells, group 2 cells being recruited at higher concentrations. The analysis of qualitative discrimination properties of cortical cells regarding the eight-odor set revealed that the discrimination power of group 2 cells was similar to that of mitral cells. By contrast, the qualitative discrimination power of group 1 cells was found to be similar to that of neuroreceptor cells. In conclusion, this pioneer approach leads us to report that olfactory cortical neurons of the frog are responsive to odors and can be clearly divided into two groups based on functional criteria. Group 1 cells, which were relatively selective, poorly discriminating but sensitive, may be mainly devoted to intensity coding. By contrast, group 2 cells, which were not very sensitive but were selective and discriminating, were hypothesized to provide minimal intensity coding and thus to be mainly devoted to qualitative discrimination tasks.

Chronic (-)baclofen or CGP 36742 alters GABAB receptor sensitivity in rat brain and spinal cord.

Administration of the GABAB receptor agonist, (-)-baclofen 10 mg kg-1, i.p. daily for 21 days to rats prevented (-)-baclofen-induced hyperpolarizing responses and synaptically-evoked late inhibitory potentials (IPSPs) in olfactory cortical neurones recorded intracellularly from 450 microns brain slices. In contrast, pre-treatment with CGP 36742 induced a significant increase in (-)-baclofen-mediated post-synaptic responses and late IPSP amplitude. In the spinal cord, the potency of (-)-baclofen in inhibiting electrically-evoked substance P-like immunoreactivity or amino acid release was significantly reduced or increased in slices from rats pre-treated with the GABAB agonist or antagonist, respectively. These data suggest that functional responses to GABAB receptor activation in the mammalian central nervous system can be up- or down-regulated.

Selective blockade of the hyperpolarization-activated cationic current (Ih) in guinea pig substantia nigra pars compacta neurones by a novel bradycardic agent, Zeneca ZM 227189

The effects of a novel bradycardic agent Zeneca ZM 227189 (4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) triazinium iodide) were tested on the inward rectifying properties of guinea-pig substantia nigra pas compacta (SNC) and guinea-pig olfactory cortical cells recorded in vitro. In SNC neurones, ZM 227189 (10-100 microM) produced a dose-dependent block of the slow anomalous rectifier; under voltage clamp, a clear reduction was seen in the amplitude of the slow inward current (Ih) relaxation evoked by negative voltage commands from a holding potential of -60 mV. ZM 227189 (50-100 microM) induced an irreversible block of the Ih current after 10-15 min exposure. A similar block of Ih was observed following application of 5 mM Cs+. ZM 227189 had little effect on other membrane properties. By contrast, in olfactory cortical neurones, ZM 227189 (100 microM) induced an increase in the input resistance (approximately 20%) and cell excitability, accompanied by a small (< 2 mV) hyperpolarization; these effects were also not reversible. Activation of the fast (K(+)-mediated) inward rectifier at negative membrane potentials remained unaffected. Lower concentrations (1-10 microM) of ZM 227189 had no obvious effect on cortical cell properties. Our data indicate that ZM 227189 is a potent and apparently selective blocker of Ih in substantia nigra neurones, but has no effect on the fast-type inward rectifier in olfactory cortical cells.

Seizures increase basic fibroblast growth factor mRNA in adult rat forebrain neurons and glia

The distribution of basic fibroblast growth factor (bFGF) mRNA in normal rat forebrain, and the influence of recurrent seizure activity on the expression of this mRNA, was evaluated using in situ hybridization and S1 nuclease protection techniques. In the untreated adult rat, hybridization of 35S-labeled bFGF cRNA densely labeled neurons in a few discrete areas including the tenia tecta, indusium gresium, and hippocampal stratum pyramidale of regions CA2 and rostromedial CA1. Neurons in the prosubiculum and rostromedial dentate gyrus stratum granulosum were lightly labeled. In addition, a diffuse distribution of autoradiographic labeling in areas such as the hippocampal molecular layers, olfactory cortical layer I, and the olfactory nerve layer was suggestive of localization in glial cells. Platinumwire hilar lesions, which did not induce seizures, increased cRNA hybridization in glial cells in primary and secondary areas of degeneration in the ipsilateral hemisphere only; hybridization was not noticeably increased in neurons in these lesion-control rats. Focal stainless-steelwire hilar lesions, which caused recurrent seizures 2–10 h postlesion, induced bilaterally distributed increases in cRNA hybridization in hippocampus, neocortex, olfactory cortex, amygdala, and septum. These seizure-dependent increases in hybridization were evident 6 h postlesion, were maximal from 12 to 24 h postlesion, and declined to near control levels by 4 days. In most regions the elevated hybridization appeared to be associated primarily with astroglia but in experimental seizure rats sacrificed 12 and 24 h postlesion hybridization was also markedly increased in the dentate gyrus granule cells and olfactory cortical neurons. These results demonstrate that recurrent seizures increase bFGF mRNA expression by both forebrain neurons and glia and implicate bFGF in the coordination of other changes in the biosynthetic activities of forebrain neurons that occur after seizures.

Trans-ACPD induces a slow post-stimulus inward tail current (I ADP) in guinea-pig olfactory cortex neurones in vitro

The metabotropic glutamate receptor agonist trans-(±)-1-amino-1,3-cyclopentanedicarboxylic acid (trans-ACPD) produced a slow, persistent excitation of guinea-pig olfactory cortical neurones in vitro, and the appearance of a prominent post-stimulus afterdepolarization. The corresponding slow inward tail current (I ADP) revealed under voltage clamp was insensitive to tetrodotoxin (or atropine) but was blocked by Cd 2+ or tetrabutylammonium. The I ADP properties resembled those of the slow inward tail current induced by muscarinic agonists in these neurones, suggesting a common intracellular transduction mechanism.