Odor regulates the expression of the mitogen-activated protein kinase phosphatase gene hVH-5 in bilateral entorhinal cortex-lesioned rats

Since it is known that several immediate early genes are induced by olfactory stimuli, we determined whether an olfactory stimulus also induces the expression of the mitogen-activated protein kinase (MAPK) phosphatase gene hVH-5 (homologue of vaccinia virus H1 phosphatase gene, clone 5), a member of a novel class of immediate early genes encoding dual-specificity protein phosphatases. The expression was studied by in situ hybridization in different brain structures involved in odor processing, in control and bilateral entorhinal cortex (EC) lesioned rats. EC-lesion did not significantly affect hVH-5 gene expression in the glomerular cell layer of the olfactory bulb (OB), while odor stimulation induced it in both control and EC-lesioned groups. In contrast, odor-induced expression of hVH-5 gene in mitral/granular cell layers was only evident after lesion of the EC. Similar results were obtained in the piriform cortex (PCx), a structure intimately connected to the mitral cell layer. In the CA1 hippocampal subfield, odor stimulation induced hVH-5 gene expression in both control and EC-lesioned animals, the increase being potentiated in lesioned rats. CA3 and dentate gyrus exhibited a similar pattern of gene expression, the odor stimulating gene expression in both control and lesioned groups. The amygdala (Am) displayed no significant change. It appears that through the induction of a MAPK phosphatase, the EC controls MAPK activities differently after odor stimulation in OB, PCx and hippocampus (Hip). The results illustrate the notion that odor representation in the brain requires plastic modifications at both anatomical and functional levels.     

Odor increases [3H]phorbol dibutyrate binding to protein kinase C in olfactory structures of rat brain. Effect of entorhinal cortex lesion

Since protein kinase C (PKC) is known to be activated in the olfactory bulb and in several limbic areas related to odor processing, we determined whether an olfactory stimulus was able to modulate the activity of PKC in animals with bilateral entorhinal cortex lesion. The translocation of PKC from the cytosol to the membrane was studied using the phorbol ester 12,13-dibutyrate ([3H]PDBu) binding in control and bilateral entorhinal cortex (EC) lesioned rats. The lesion of EC per se did not significantly affect [3H]PDBu binding in any of the brain structures analyzed, while odor stimulation induced it in both control and EC-lesioned groups in the external plexiform layer of the olfactory bulb. In contrast, an odor-induced increase of [3H]PDBu binding in internal glomerular layer of the olfactory bulb was only observed in EC lesioned animals. Similar results were obtained in the piriform cortex. In both CA1 and CA3 hippocampal subfields, odor stimulation induced an increase of [3H]PDBu binding in both control and EC-lesioned animals, the increase being potentiated only in CA1 of lesioned rats. The dentate gyrus and the amygdala exhibited a similar pattern of [3H]PDBu binding, showing a significant increase exclusively in EC-lesioned animals after odor stimulation. The results strongly suggest that the EC plays a key role in odor processing. PKC appears to play an important role in responding to the activation of lipid second messengers, which have been described to be involved in the processing of odor stimuli in several structures of the olfactory pathway.     

Alteration of dopamine D1 receptor-mediated motor inhibition and stimulation during development in rats is associated with distinct patterns of c-fos mRNA expression in the frontal-striatal circuitry

Dopamine D1 receptors have been implicated in various neurodevelopmental disorders, including attention-deficit/hyperactivity disorder. However, little is known about potential late maturational changes of the motor inhibitory and stimulatory role of these receptors. Here, we investigated the effects of a full and selective D1 receptor agonist, SKF-81297, on motor activity and expression of the plasticity-associated gene, c-fos, in the prefrontal cortex and striatum of juvenile and adolescent male rats. In general, SKF-81297 produced a biphasic effect on motor activity (locomotor and rearing activity), which consisted of an initial short inhibition followed by a long-lasting stimulation. These effects were dose- and age- dependent. The inhibitory phase was more pronounced in adolescent than in juvenile rats whereas the opposite was true for the stimulatory phase. During the initial inhibitory phase of the drug, c-fos mRNA expression was increased in the prefrontal cortex of juvenile rats but reduced in adolescent rats. There was also an increase in c-fos mRNA expression in the medial-dorsal striatum and olfactory tubercle, which was more evident in juvenile rats. In contrast, during the stimulatory phase, c-fos mRNA expression was increased in both the dorsal and ventral striatum, especially in the nucleus accumbens, as well as in the prefrontal cortex, in both age groups. The increase of c-fos mRNA in the dorsal striatum, however, was more pronounced in juvenile rats. These results indicate the presence of two distinct D1 receptor populations within the frontal-striatal circuitry, which have opposite effects on motor activity, and which have different maturational profiles.     

Olfactory discrimination ability and brain expression of c-fos, Gir and Glut1 mRNA are altered in n-3 fatty acid-depleted rats

The long-chain polyunsaturated n-3 fatty acids (n-3 PUFA), particularly docosahexaenoic acid (DHA), are abundantly present in the central nervous system and play an important role in cognitive functions such as learning and memory. We, therefore, investigated the effects of n-3 PUFA-depletion in rats (F2 generation) on the learning of an olfactory discrimination task, progressively acquired within a four-arm maze, and on the mRNA expression of some candidate genes, i.e., c-fos, Gir and glucose transporter (Glut1), which could reflect the level of cerebral activity. We observed that DHA contents were dramatically decreased in the olfactory bulb, the piriform cortex and the neocortex of n-3-depleted rats. Furthermore, the n-3 deficiency resulted in a mild olfactory learning impairment as these rats required more days to master the olfactory task compared to control rats. Real-time RT-PCR experiments revealed that the training induced the expression of c-fos mRNA in all the three regions of the brain whereas Gir and Glut1 mRNA were induced only in olfactory bulb and neocortex. However, such an increase was less marked in the n-3-deficient rats. Taken together, these results allow us to assume that the behavioural impairment in n-3-deficient rats is linked to the depletion of n-3 fatty acids in brain regions processing olfactory cues. Data are discussed in view of the possible role of some of these genes in learning-induced neuronal olfactory plasticity.     

Olfactory input to the parahippocampal region of the isolated guinea pig brain reveals weak entorhinal-to-perirhinal interactions

The processing of olfactory inputs by the parahippocampal region has a central role in the organization of memory in mammals. The olfactory input is relayed to the hippocampus via interposed synapses located in the piriform and entorhinal cortices. Whether olfactory afferents directly or indirectly project to other areas of the parahippocampal region beside the entorhinal cortex (EC) is uncertain. We performed an electrophysiological and imaging study of the propagation pattern of the olfactory input carried by the fibres that form the lateral olfactory tract (LOT) into the parahippocampal region of the in vitro isolated guinea pig preparation. Laminar analysis was performed on field potential depth profiles recorded with 16-channel silicon probes at different sites of the insular-parahippocampal cortex. The LOT input induced a large amplitude polysynaptic response in the lateral EC. Following appropriate LOT stimulation, a late response generated by the interposed activation of the hippocampus was observed in the medial EC. LOT stimulation did not induce any local response in area 36 of the perirhinal cortex (PRC), while a small amplitude potential with a delay similar to the lateral EC response was inconsistently observed in PRC area 35. No PRC potentials were observed following the responses evoked by LOT stimulation in either the lateral or the medial EC. These findings were substantiated by current source density analysis of PRC laminar profiles. To further verify the absence of EC-to-PRC field interactions after LOT stimulation, high-resolution optical imaging of neuronal activity was performed after perfusion of the isolated brain with the voltage-sensitive dye RH-795. The optical recordings confirmed that olfactory-induced activity in the EC does not induce massive PRC activation. The present findings suggest that the olfactory input into the parahippocampal region is confined to the entorhinal cortex. The results also imply that, as demonstrated for the PRC-to-EC pathway, the propagation of neuronal activity from the EC to the PRC is hindered, possibly by a powerful inhibitory control generated within the EC.     

Brain endothelial cell production of a neuroprotective cytokine, interleukin-6, in response to noxious stimuli

Changes in the expression of immediate early gene c-fos by noxious mechanical stimulation to the mandibular incisor pulp of rats were immunohistochemically examined in the hippocampus (Ammon's horn and dentate gyrus) and the retrohippocampus (subiculum, presubiculum, parasubiculum and entorhinal cortex). The highest control levels were found in subiculum, CA1, dentate and deep medial entorhinal cortex. Lower, but substantial levels were present in the other areas. Whereas weak dentinal stimulation caused increases in c-fos expression in some regions which were not statistically significant, strong tooth pulp stimulation caused a bilateral decrease in c-fos expression in every region except contralateral subiculum. These decreases reached statistical significance in superficial layer parasubiculum bilaterally (p<0.01), bilateral CA1 and ipsilateral side of superficial layer of medial entorhinal cortex (p<0.05). We suggest that inhibitory circuitry in hippocampal formation regions may be activated by peripheral noxious somatosensory inputs and this change in activity is accompanied by a change in the expression of the immediate early gene, c-fos.     

Spatiotemporal distribution of a late synchronized activity in olfactory pathways following stimulation of the olfactory bulb in rats

The evoked potential recorded in the rat piriform cortex in response to electrical stimulation of the olfactory bulb is composed of an early component occasionally followed by a late component (60–70 ms). We previously showed that the late component occurrence was enhanced following an olfactory learning. In the present study carried out in naive rats, we investigated the precise conditions of induction of this late component, and its spatiotemporal distribution along the olfactory pathways. In the anaesthetized rat, a stimulating electrode was implanted in the olfactory bulb. Four recording electrodes were positioned, respectively, in the olfactory bulb, the anterior and posterior parts of the piriform cortex, and the entorhinal cortex. Simultaneous recording of signals evoked in the four sampled structures in response to stimulation of the olfactory bulb revealed that the late component was detected in anterior and posterior piriform cortex as well as in entorhinal cortex, but not in the olfactory bulb. The late component occurred reliably for a narrow range of low intensities of stimulation delivered at frequencies not exceeding 1 Hz. Comparison of late component amplitude and latency across the different recorded sites showed that this component appeared first and with the greatest amplitude in the posterior piriform cortex. In addition to showing a functional dissociation between anterior and posterior parts of the piriform cortex, these data suggest that the posterior piriform cortex could be the locus of generation of this late high amplitude synchronized activity, which would then propagate to the neighbouring regions.     

Evolution of brain infarction after transient focal cerebral ischemia in mice.

The evolution of brain infarction after transient focal cerebral ischemia was studied in mice using multiparametric imaging techniques. One-hour focal cerebral ischemia was induced by occluding the middle cerebral artery using the intraluminal filament technique. Cerebral protein synthesis (CPS) and the regional tissue content of adenosine triphosphate (ATP) were measured after recirculation times from 0 hours to 3 days. The observed changes were correlated with the expression of the mRNAs of hsp-70, c-fos, and junB, as well as the distribution of DNA double-strand breaks, visualized by TUNEL. At the end of 1 hour of ischemia, protein synthesis was suppressed in a larger tissue volume than ATP in accordance with the biochemical differentiation between core and penumbra. Hsp70 mRNA was selectively expressed in the cortical penumbra, whereas c-fos and junB mRNAs were increased both in the lateral part of the penumbra and in the ipsilateral cingulate cortex with normal metabolism. During reperfusion after withdrawal of the intraluminal filament, suppression of CPS persisted except in the most peripheral parts of the middle cerebral artery territory, in which it recovered between 6 hours and 3 days. ATP, in contrast, returned to normal levels within 1 hour but secondarily deteriorated from 3 hours on until, between 1 and 3 days, the ATP-depleted area merged with that of suppressed protein synthesis leading to delayed brain infarction. Hsp70 mRNA, but not c-fos and junB, was strongly expressed during reperfusion, peaking at 3 hours after reperfusion. TUNEL-positive cells were detected from 3 hours on, mainly in areas with secondary ATP depletion. These results stress the importance of an early recovery of CPS for the prevention of ischemic injury and suggest that TUNEL is an unspecific response of delayed brain infarction.     

Differential expression of immediate early genes in distinct layers of rat cerebral cortex after selective immunolesion of the forebrain cholinergic system

The aim of this study was to show whether reduction or loss of cortical cholinergic activity results in any particular change in the expression of the proto-on-cogenes c-fos and/or c-jun. To produce cortical cholinergic hypofunction, the monoclonal antibody, 1921gG, to the low-affinity nerve growth factor receptor p75^NGFR coupled to a cytotoxin, saporin, was used as an efficient and selective immunotoxin for cholinergic neurons in rat basal forebrain. Brain sections of adult rats that had received an intracerebro-ventricular injection of 4 μg of the 1921gG-saporin were subjected to in situ hybridization using oligonucleotides to detect c-fos and c-jun mRNA. Autoradiographs obtained were evaluated by quantitative image analysis. Seven days following injection of the immunotoxin there was a dramatic loss in acetylcholinesterase staining in frontal, parietal, piriform, temporal, and occipital cortices, hippocampus, and olfactory bulb, but not in the striatum and cerebellum. In situ hybridization revealed a considerable increase in the level of c-fos mRNA in the lateral septum following the cholinergic lesion, whereas in the medial septum both c-fos and c-jun mRNA were elevated. Immunolesioning led to a distinct and specific increase in the level of c-jun but not c-fos mRNA in the parietal and occipital cortex that was restricted to cortical layer IV. These data suggest that reduced cortical cholinergic activity differentially regulates expression of c-fos/c-jun genes in distinct cortical regions of the rat brain. © 1994 Wiley-Liss, Inc.     

Regional alterations of the NO/NOS system in the aging brain: a biochemical, histochemical and immunochemical study in the rat

We have used several approaches (immunohistochemistry and enzyme histochemistry, Western blotting, biochemical assay of Ca(2+)-dependent catalytic activity) in order to detect differences in neuronal nitric oxide synthase (nNOS) expression and activity in various brain regions of young-adult (4-month-old) and aged (28-month-old) rats. In most of the brain regions examined (striatum, neocortex, olfactory cortex and hippocampus) some significant decrease in the density per unit area of nNOS neurons, detected either through immunohistochemistry or enzyme histochemistry, was observed in aged rats. However, only in the striatum and olfactory cortex this was accompanied by a significant decrease of the catalytic activity of the constitutive, Ca(2+)-dependent NOS form. In these two regions, the relative level of expression of nNOS protein was also significantly decreased, as assessed by Western blotting of proteic extracts from young-adult and aged rats. Other observed differences were a paler stain of neurons in some brain areas of the aged rats and differences of cellular compartmentalization of the protein in the same rats, as assessed through confocal microscopy. The present observations demonstrate that the expression and activity of nNOS show regionally-specific alterations in the brain of aged healthy rats, with a trend towards decrease, rather than toward increase as suggested by some previous reports. Therefore, hypotheses implicating nitric oxide increase in brain aging should be reconsidered on the basis of a clear-cut distinction between the physiological and the pathological aspects of the aging process.     

Amygdala stimulation ameliorates memory impairments and promotes c-Fos activity in fimbria-fornix-lesioned rats

Recently we provided data showing that amygdala stimulation can ameliorate spatial memory impairments in rats with lesion in the fimbria-fornix (FF). The mechanisms for this improvement involve early gene expression and synthesis of BDNF, MAP-2, and GAP43 in the hippocampus and prefrontal cortex. Now we have studied which brain structures are activated by the amygdala using c-Fos as a marker of neural activation. First, we studied neuronal activation after tetanic stimulation to the amygdala in intact rats. We then carried out a second study in FF-lesioned rats in which the amygdala was stimulated 15 min after daily spatial memory training in the water maze. Our results showed that amygdala stimulation produces widespread brain activation, that includes cortical, thalamic, and brain stem structures. Activation was particularly intense in the dentate gyrus and the prefrontal cortex. Training in the water maze increased c-Fos positive nuclei in the dentate gyrus of the hippocampus and in medial prefrontal cortex. Amygdala stimulation to trained FF-lesioned rats induced an increase of neural activity in the dentate gyrus and medial prefrontal cortex relative to the FF-lesioned, but not stimulated group, like the c-Fos activity seen in trained control rats. Based on these and previous results we explain the mechanisms of amygdala reinforcement of neural plasticity and the partial recovery of spatial memory deficits.     

Increased BDNF and trk-B mRNA expression in cortical and limbic regions following formation of a social recognition memory

Brain-derived neurotrophic factor (BDNF) and its receptor, tyrosine receptor kinase (trk-B), play important roles in neural plasticity, long-term potentiation and memory formation. Sheep form a selective recognition memory for their lambs within 2 h of birth. Initially, this memory is exclusively based on olfactory cues; however, as it consolidates over a 12-h recognition period it extends to incorporate visual cues. We investigated whether changes in BDNF and trk-B mRNA expression occurred in both olfactory and visual processing systems at 4.5 h postpartum, 2-3 h after the behavioural manifestations of an olfactory recognition memory were found. Animals that formed a recognition memory showed increased BDNF mRNA expression in the inferior part of the temporal cortex, subfield CA1 of the hippocampus, the diagonal band, basolateral amygdala and the anterior cingulate, medial frontal, entorhinal and pyriform cortices. No increases were observed in either the olfactory bulbs or the dentate gyrus. Expression of trk-B mRNA was significantly increased only in the medial temporal, entorhinal and pyriform cortices. These findings demonstrate that by 2-3 h following the initial formation of olfactory recognition memory there are BDNF/trk-B-mediated plasticity changes in brain areas involved in the consolidation of olfactory memory (the pyriform and entorhinal cortices). However, similar changes also occur in areas of the brain involved in visual memory, face and object recognition (the temporal cortex, entorhinal cortex, hippocampal subfield CA1 and basolateral amygdala), and in areas of the brain with integrative and attentional functions (the medial frontal and anterior cingulate cortices and diagonal band). This suggests that reorganization of neural circuits underlying the visual recognition of lambs or the integration of olfactory/visual information is occurring even at this time even though accurate behavioural recognition at this stage can only be made using olfactory cues.     

Fos and jun in rat central amygdaloid nucleus and paraventricular nucleus after stress.

The present paper describes the effect of capsaicin-induced stressful stimulus on the expression of immediate early genes (IEGs) c-fos, c-jun, junB and junD in the hypothalamic paraventricular nucleus (PVN) and the central amygdaloid nucleus (ACe) using in situ hybridization. Stress caused an intense expression of c-fos, c-jun and junB especially in the PVN and ACe and also a clear induction of junD was observed in the PVN. This suggests that the PVN and the ACe are two major targets of stress in the brain. The intense expression of the IEGs in the ACe and PVN suggests that stress may affect neurotransmitter gene expression through Fos and Jun proteins in both these nuclei.     

Effects of unilateral cortex lesions on gene expression of rat cortical cholecystokinin neurons.

In rat neocortex, the gene encoding preprocholecystokinin is expressed in interneurons which also synthetize gamma-aminobutyric acid. An injury to the meninges and the underlying cortex increased the concentration of mRNA coding for preprocholecystokinin in all ipsilateral cortical areas. Simultaneous treatment of the rats with the anti-inflammatory agent diclofenac did not affect the injury-induced change in gene expression indicating that inflammatory processes were not involved. The injury also enhanced the expression of the immediate early gene c-fos in the ipsilateral cortex in a time-dependent manner. There was an increase in c-fos mRNA 1 h after the operation, which was no longer observed 3 h later. Twenty-four hours after the operation, cells containing c-fos mRNA were found in cortical layers II, III, V and VI. The neurons which showed an increased expression of preprocholecystokinin were also in these layers. The N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 prevented the injury-induced increases in both preprocholecystokinin and c-fos gene expression, indicating that stimulation of this glutamate receptor subtype may initiate the changes in expression of both genes. It is hypothetized that the immediate early gene c-fos is activated first and this then leads to the increase in preprocholecystokinin mRNA.     

Regulation of c-Fos mRNA and fos protein expression in olfactory bulbs from unilaterally odor-deprived adult mice

Odorant deprivation, produced by unilateral naris closure, profoundly reduces tyrosine hydroxylase (TH) expression within intrinsic olfactory bulb dopamine neurons. The TH gene contains an AP-1 site, which interacts with the product of the immediate early gene, c-fos. c-Fos exhibits activity dependent regulation in the CNS. The hypothesis that odorant stimulation and deprivation might modify c-fos expression in TH neurons was tested in adult CD-1 mice, subjected to unilateral naris closure. After 2 months, naris closed and control mice were exposed to either clean air for 60 min or clean air for 60 min followed by 30 min of alternating exposure to 10% isoamyl acetate (1 min) and air (4 min). A parallel reduction occurred in TH and fos expression (both c-fos mRNA and fos-like immunoreactivity) in the glomerular layer of the odorant-deprived olfactory bulb. Odor stimulation induced a short-lived increase in c-fos mRNA and fos-like immunoreactivity in olfactory bulbs contralateral to naris closure. The increase in fos expression was region-specific in the glomerular layer but more diffuse in mitral and granule cell layers. In olfactory bulbs ipsilateral to naris closure, odor stimulation also induced c-fos mRNA expression in the mitral and granule cell layers and sparsely within limited periglomerular regions. Odor induced expression in mitral and granule cell layers may represent increased centrifugal activity acting on as yet unknown genes. These results suggest a correlation between c-fos mRNA expression and increased neuronal activity in the olfactory bulb which, in turn, acts to regulate TH expression in periglomerular neurons.     

Developmental changes in c-fos expression to an age-specific social stressor in infant rats.

Young rats become immobile when exposed to a potentially infanticidal adult male rat. Male-induced immobility declines during the preweaning period, paralleling the decrease in infanticidal threat. To investigate the neural substrates underlying the developmental change in immobility, male-induced expression of the immediate-early gene c-fos was assessed on postnatal days 7, 14 and 21. A huddle of three young rats was exposed to an adult male behind a screen. As control, three littermates were put in the testing chamber but not exposed to the male. On day 7, male exposed and control pups were immobile most of the time and c-fos expression did not differ between conditions. On day 14, rats in the presence of the male stopped ongoing behaviors and became immobile. They had significantly higher c-fos expression in the paraventricular nucleus of the hypothalamus, the amygdala, the periaqueductal gray, and the locus ceruleus. On day 21, the male-exposed rats that were immobile had elevated c-fos expression in a similar pattern as on day 14, however, different nuclei of the amygdala were activated. In contrast, male-exposed 21-day-old rats that showed control levels of immobility did not have elevated c-fos expression in these areas. These results demonstrate that male exposure induced c-fos expression in brain areas of young rats in an age-specific pattern. Some of the activated brain areas seem to have contributed to immobility. Differential activation of neuronal populations may underlie developmental changes in defensive immobility during early ontogeny.     

Cue valence representation studied by Fos immunocytochemistry after acquisition of a discrimination learning task

The piriform cortex (PCx) and related structures such as hippocampus and frontal cortex could play an important role in olfactory memory. We investigated their involvement in learning the biological value of an odor cue, i.e. predicting reward or non-reward in a two-odor discrimination task. Rats were sacrificed after stimulation by either rewarded or non-rewarded odor and Fos immunocytochemistry was performed. The different experimental groups of rats did not show strongly differentiated Fos expression pattern in either the PCx or the hippocampus. A few differences were noted in frontal areas. In the ventro-lateral orbital cortex, rats, ramdomly rewarded during the conditionning had a higher Fos level in comparison with other groups. In infralimbic cortex, rats, which learned the reward value of the olfactory cue and were water-reinforced the day of sacrifice, showed a higher Fos expression. Data are discussed in view of the olfactory learning paradigm and of the accuracy of the control groups used in the present experimental design. The behavioural conditions leading to Fos expression are further discussed since Fos is a marker of learning-induced plasticity as well as a general activity marker which can be activated by a wide range of stimuli not directly linked to memory.     

Sprouting fibers gain access to circuitry transsynaptically altered by kindling

In intact rats, “kindling” stimulation of the entorhinal cortex (EC) resulted, after an average of 23 daily stimulations, in the appearance of generalized convulsions. When the primary site of kindling in the EC was electrolytically destroyed and 14 days were permitted for the contralateral EC to sprout in response to the lesion, kindling stimulation of this surviving EC evoked fully developed motor seizures in 9 of 10 animals with the first or second stimulation. However, if the primary site of kindling was not destroyed, kindling via the contralateral EC required an average of more than five stimulations. Furthermore, if sprouting was induced by a unilateral EC lesion prior to any kindling stimulation, kindling via the surviving “sprouted” EC contralateral to the lesion proceeded at a rate not significantly different from normal. Finally, the essentially immediate expression of seizure-evoking capabilities via the EC contralateral to a lesion was not observed if kindling via the secondary site was initiated 1 day after a primary site lesion, at a time prior to the completion of sprouting. These results were consistent with the hypothesis that EC kindling results in transsynaptic alterations either in the immediate targets of the EC (e.g., the dentate gyrus) or further “downstream” synaptically, and that destruction of the primary site of kindling results in the sprouting of projections which gain access to the altered circuitry.     

Expression of Fos in the piriform cortex after acquisition of olfactory learning: An immunohistochemical study in the rat

The piriform cortex (PCx), the main area of the primary olfactory cortex, is assumed to play a role in olfactory memory. Involvement of this paleocortex in mnesic processes was investigated by using Fos immunocytochemistry after acquisition of a two-odor discrimination task. Trained rats had to associate one odor of a pair with water reward while pseudo-trained rats were randomly rewarded. We further used non-trained rats and home cage control animals to determine the effect of manipulation and basal Fos level respectively. Except in control rats, Fos immunoreactivity was mainly distributed in brain areas involved in olfactory processing, learning and arousal. The trained, pseudo-trained, and non-trained rats showed a high Fos labeling in the entire PCx. However, quantitative analysis demonstrated a statistically higher Fos immunoreactivity in the anterior PCx in comparison with the posterior PCx for these rats. Furthermore, behavioral data allowed us to distinguish two groups of trained rats according to the number of days required to acquire the task. Rats with slow acquisition showed a higher Fos immunoreactivity in the whole PCx in comparison with the rats exhibiting a fast acquisition. Our findings support the assumption of a PCx rostro-caudal heterogeneity which could sustain differential information processing.     

Effect of prefrontal cortex inactivation on behavioral and neurochemical abnormalities in rats with excitotoxic lesions of the entorhinal cortex

Morphological studies report reductions in the volume of medial temporal lobe structures and the prefrontal cortex in subjects with schizophrenia. The present study was performed to clarify the role of prefrontal-temporo-limbic system in the manifestation of psychosis, using entorhinal cortical lesion rats as a vulnerability animal model. Quinolinic acid (lesion group) or phosphate buffer (sham group) was infused into the left entorhinal cortex (EC) of male Wistar rats. On the 28th postoperative day, methamphetamine (MAP; 1 mg/kg, i.p.)-induced dopamine (DA) release in the nucleus accumbens (NAC) and the basolateral amygdala (BLA), as well as locomotor activity and prepulse inhibition (PPI), was measured following microinfusion of lidocaine or the cerebrospinal fluid (CSF) into the medial prefrontal cortex (mPFC). Lesions of the EC resulted in enhancement of MAP-induced DA release in the NAC and BLA. Further analysis revealed that the enhancement by EC lesions of MAP-induce DA release in the NAC was particularly evident in the lidocaine-infused rats. EC lesions also enhanced MAP-induced locomotor activity, especially in the lidocaine-treated animals. By contrast, infusion of lidocaine into mPFC attenuated MAP-induced DA release in the BLA, irrespective of the lesion status. Both EC lesions and lidocaine infusion disrupted PPI. These results indicate that inactivation of the mPFC, as well as structural abnormalities in the EC, leads to dysregulation of DAergic neurotransmissions in the limbic regions. The implications of these findings in relation to the neural basis for psychosis vulnerability are discussed.