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Pallial expression of Enc1 RNA in postnatal mouse telencephalon.

We analysed the pallial expression pattern of Enc1 (a member of the kelch family of genes) in postnatal mice (P1-P10). At early developmental stages this gene plays a role in the histogenesis of cortical structures [M.C. Hernández, P.J. Andrés-Barquin, S. Martínez, A. Bulfone, J.L.R. Rubenstein, M.A. Israel, Enc1: novel mammalian kelch-related gene specifically expressed in the nervous system encodes an actino-binding protein, J. Neurosci. 17 (1997) 3038-3051]. A restricted expression of Enc1 was found in the mouse pallium, notably within claustroamygdaloid derivatives of the lateral pallium and in some cortical layers in the lateral, dorsal and medial pallium sectors, with distinct regional differences. The strongest cortical expression was found in isocortical layer II and in the piriform cortex, anterior olfactory area and olfactory bulb mitral cells. The lowest signal occurred in the retrosplenial cortex. The subgranular layers V/VI were also positive, particularly layer V, with clearcut areal differences. The hippocampal CA3/CA4 areas and the dentate gyrus were strongly positive. The dorsolateral (core) portion of the claustrum and dorsal endopiriform nucleus were moderately positive, as were the amygdaloid lateral and basolateral nuclei.

Age Factors↗

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

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

Adolescent↗

An infant with macrocephaly, abnormal neuronal migration and persistent olfactory ventricles.

An asphyxiated male infant was delivered by cesarean section at 38 weeks gestation. The patient was macrocephalic with clinical evidence of fetal immobility syndrome. He died aged two days. Autopsy revealed excessive brain weight, pachygyria, enlarged olfactory tracts and hypoplastic optic nerves. Microscopy revealed evidence of impaired neuronal migration throughout the cortex. The olfactory bulbs showed persistence of the primitive olfactory ventricles and absence of olfactory glomeruli. There was persistence of the fetal connection between lateral and olfactory ventricles. The lateral geniculate nuclei, inferior olivary nuclei and dentate nuclei of the cerebellum were abnormally formed. Relevant aspects of fetal brain development and clinical neuropathologic syndromes are discussed.

Abnormalities, Multiple↗

Effects of acute and chronic cocaine administration on somatostatin level and binding in the rat brain.

The effects of acute and chronic cocaine (40 mg/Kg i.p.) in vivo administration, on 125I-Tyr11-somatostatin binding and somatostatin-like immunoreactivity (SLI) in the rat frontoparietal cortex, hippocampus and olfactory bulb were explored. Acute and chronic cocaine administration did not affect the levels of SLI in the three brain areas studied. Acute cocaine administration resulted in an 55% and 32% decrease in the total number of specific somatostatin receptors in the hippocampus and olfactory bulb respectively, but not in the frontoparietal cortex. Somatostatin receptor affinity increased in the hippocampus and was unaltered in frontoparietal cortex and olfactory bulb. After two weeks of daily cocaine injections the somatostatin binding in the hippocampus and olfactory bulb returned to control values. The in vitro addition of cocaine to a brain membrane preparation obtained from untreated rats did not markedly affect somatostatin binding characteristics. These results are suggestive of a possible role for somatostatin in the limbic structures as a response to cocaine administration.

Animals↗

Requirement for the lpA1 lysophosphatidic acid receptor gene in normal suckling behavior.

Although extracellular application of lysophosphatidic acid (LPA) has been extensively documented to produce a variety of cellular responses through a family of specific G protein-coupled receptors, the in vivo organismal role of LPA signaling remains largely unknown. The first identified LPA receptor gene, lp(A1)/vzg-1/edg-2, was previously shown to have remarkably enriched embryonic expression in the cerebral cortex and dorsal olfactory bulb and postnatal expression in myelinating glia including Schwann cells. Here, we show that targeted deletion of lp(A1) results in approximately 50% neonatal lethality, impaired suckling in neonatal pups, and loss of LPA responsivity in embryonic cerebral cortical neuroblasts with survivors showing reduced size, craniofacial dysmorphism, and increased apoptosis in sciatic nerve Schwann cells. The suckling defect was responsible for the death among lp(A1)((-/-)) neonates and the stunted growth of survivors. Impaired suckling behavior was attributable to defective olfaction, which is likely related to developmental abnormalities in olfactory bulb and/or cerebral cortex. Our results provide evidence that endogenous lysophospholipid signaling requires an lp receptor gene and indicate that LPA signaling through the LP(A1) receptor is required for normal development of an inborn, neonatal behavior.

Animals↗

Interactions of phencyclidine receptor agonist MK-801 with dopaminergic system: regional studies in the rat.

Interactions of the potent phencyclidine receptor agonist MK-801 with the dopaminergic system were examined in various brain regions in the rat. MK-801 increased dopamine (DA) metabolism in the pyriform cortex, entorhinal cortex, prefrontal cortex, striatum, olfactory tubercle, amygdala, and septum without affecting DA metabolism in the cingulate cortex and nucleus accumbens. In pyriform cortex and amygdala, MK-801 was more potent than phencyclidine at increasing DA metabolism. Local injections of MK-801 into ventral tegmental area and into the amygdala/pyriform cortex interface indicated that MK-801 may act at the cell body as well as the nerve terminal level to increase DA metabolism and that ongoing dopaminergic neuronal activity is a prerequisite for full drug action.

3,4-Dihydroxyphenylacetic Acid↗

Olfactory inputs activate the medial entorhinal cortex via the hippocampus.

The lateral and medial regions of the entorhinal cortex differ substantially in terms of connectivity and pattern of activation. With regard to olfactory input, a detailed and extensive physiological map of the olfactory projection to the entorhinal cortex is missing, even if anatomic studies suggest that the olfactory afferents are confined to the lateral and rostral entorhinal region. We studied the contribution of the medial and lateral entorhinal areas to olfactory processing by analyzing the responses induced by lateral olfactory tract stimulation in different entorhinal subfields of the in vitro isolated guinea pig brain. The pattern of synaptic activation of the medial and lateral entorhinal regions was reconstructed either by performing simultaneous multisite recordings or by applying current source density analysis on field potential laminar profiles obtained with 16-channel silicon probes. Current source density analysis demonstrated the existence of a direct monosynaptic olfactory input into the superficial 300 microm of the most rostral part of the lateral entorhinal cortex exclusively, whereas disynaptic sinks mediated by associative fibers arising from the piriform cortex were observed at 100-350 microm depth in the entire lateral aspect of the cortex. No local field responses were recorded in the medial entorhinal region unless a large population spike was generated in the hippocampus (dentate gyrus and CA1 region) by a stimulus 3-5x the intensity necessary to obtain a maximal monosynaptic response in the piriform cortex. In these conditions, a late sink was recorded at a depth of 600-1000 microm in the medial entorhinal area (layers III-V) 10.6 +/- 0.9 (SD) msec after a population spike was simultaneously recorded in CA1. Diffuse activation of the medial entorhinal region was also obtained by repetitive low-intensity stimulation of the lateral olfactory tract at 2-8 Hz. Higher or lower stimulation frequencies did not induce hippocampal-medial entorhinal cortex activation. These results suggest that the medial and the lateral entorhinal regions have substantially different roles in processing olfactory sensory inputs.

Action Potentials↗

The effect of venlafaxine treatment on the behavioural and neurochemical changes in the olfactory bulbectomised rat.

In the present study, the effect of chronic treatment with venlafaxine on beta1 and 5-HT2 receptor populations was examined in the frontal cortex of olfactory bulbectomised (OB) and sham operated (SO) animals. The effect of these drugs on the behaviour of the animals on the elevated plus maze and the "open field" was also assessed. Removal of the bulbs resulted in a characteristic increase in locomotor activity in the OB animals in the "open field" which was reversed by chronic venlafaxine treatment. Venlafaxine produced a slight reduction in the number of open arm entries made by the OB animals although this failed to reach significance. Maximum change in temperature from baseline, following a single dose of 8-OH-DPAT (1.5 mg kg(-1) SC), was used to assess the function of the 5-HT1A receptors. Chronic venlafaxine treatment had no effect on the hypothermic response to 8-OH-DPAT in the present study. A decrease in the affinity of beta1-adrenoceptors was found following olfactory bulbectomy and this was normalised by treatment with venlafaxine. No bulbectomy-induced changes were evident 32 days post surgery in beta1-adrenoceptor density; however, chronic treatment with venlafaxine significantly reduced the density of these receptors in the OB animals. Olfactory bulbectomy did not produce any changes in 5-HT2 receptor populations but venlafaxine administration significantly reduced the density of these receptors in both SO and OB animals. The findings of the present study further validate the usefulness of the OB as an animal model, for the detection of antidepressants from a wide variety of classes.

Animals↗

Synaptic organization of olfactory inputs and local circuits in the entorhinal cortex: a current source density analysis in the cat.

The distribution of the olfactory afferents within the ventrolateral part of the entorhinal cortex (EC) was studied by means of field potentials evoked by stimulation of the olfactory bulb (OB) and the olfactory cortex (PPC). Depth profiles of the field potentials evoked by OB or PPC stimulation were studied using current source density analysis. After OB or PPC stimulation an early superficial sink-deep source configuration was found, which some time later reversed into a superficial source-deep sink. Both OB and PPC activated mainly the superficial dendrites of the cells of layers II and III. In layers II and III evidence for strong recurrent inhibition was found, using double pulse stimulation. The results indicate that there exists a common basic design of the synaptic organization of the olfactory areas of the base of the brain extending to the EC.

Action Potentials↗

Olfactory response in the temporal cortex of the elderly measured with near-infrared spectroscopy: a preliminary feasibility study.

The pathway for the olfactory response may be affected at an early stage of Alzheimer's disease. Measurement of the olfactory response in the elderly is therefore of particular interest. In this feasibility study, near-infrared spectroscopy was used to measure the olfactory response in 21 patients aged 56 to 79 years. Eight subjects had no memory complaints whereas 13 had subjective memory complaints, mild cognitive impairment, or very mild Alzheimer's disease. The optodes were placed over the temporal lobe, with the emitting optode over the pole and the receiving optode over the superior gyrus. The response to vanilla (1% in sterile H2O) in a test tube held immediately beneath the nostrils was compared to the response to sterile H2O only. Four control subjects had a clearly definable response with increased oxyhemoglobin and decreased deoxyhemoglobin bilaterally. The response was measured as the sum of the deviation of oxygenated and deoxygenated hemoglobin from baseline mean. With a cut-off determined after examination of responses to vanilla and sham stimulus, group difference was significant for response to vanilla (chi2 test, P = 0.03). Response amplitudes to vanilla in the patient group were within the range of those to sham stimuli.

Aged↗

Comparison of the effects of cocaine and other inhibitors of dopamine uptake in rat striatum, nucleus accumbens, olfactory tubercle, and medial prefrontal cortex.

It is thought that inhibition of dopamine reuptake into neurons may play a major role in the mechanisms by which cocaine produces its reinforcing effects. The striatum, while rich in dopamine terminals, is not implicated in drug reinforcement, whereas the mesolimbic dopamine pathway appears to play a primary role. It is therefore possible that the properties and drug sensitivities of the dopamine uptake systems in the nigrostriatal, mesolimbic, and mesocortical tracts differ. The effects of cocaine, GBR 12909, amfonelic acid, and methylphenidate on dopamine uptake in the striatum, nucleus accumbens, olfactory tubercle, and medial prefrontal cortex were examined. Over 80% of the dopamine uptake in each of the 4 regions was sodium-dependent and exhibited Km values of approximately 100 nM. Cocaine, GBR 12909, amfonelic acid, and methylphenidate each biphasically inhibited uptake in the striatum, nucleus accumbens and olfactory tubercle with GBR 12909 and amfonelic acid being approximately 50-fold more potent than cocaine or methylphenidate. In the medial prefrontal cortex, cocaine and GBR 12909 could inhibit only about 40% of the [3H]dopamine uptake. There are similarities in the properties and drug sensitivities of the dopamine uptake systems in brain areas which are implicated in drug reinforcement and those which are not.

Animals↗

Immunohistochemical localization of an inositol 1,4,5-trisphosphate receptor, P400, in neural tissue: studies in developing and adult mouse brain.

The immunohistochemical localization of P400/inositol 1,4,5-trisphosphate (InsP3) receptor protein was studied in developing and adult mouse brain by using monoclonal antibodies. The developmental expression pattern of P400/InsP3 receptor protein differed among different classes of neurons. It was first detected in the somata of immature Purkinje cells at embryonic day 17, in the ventrolateral region of the posterior vermis in the cerebellum. Axonal immunoreactivity within the cerebellar nuclei was first present at postnatal day 3. Neurons in the retrosplenial cortex, the anterior olfactory nucleus, and the CA1 region of the hippocampus expressed immunoreactivity earlier than other regions of the brain. In the adult brain, not only the Purkinje cell but also many other types of cells in many areas of the brain expressed P400/InsP3 receptor, though to a lesser extent. These included the neurons in the striatum, globus pallidus, nucleus accumbens septi, anterior olfactory nucleus, olfactory tubercle, precommissural hippocampus, hippocampus, substantia nigra, cerebral cortex, pons, and certain hypothalamic nuclei. Forebrain cortical regions that receive afferents from the olfactory bulb, such as the anterior olfactory nucleus, olfactory tubercle, prepiriform cortex, entorhinal cortex, and amygdala, exhibited distinct immunoreactivity, while olfactory bulb was almost devoid of staining. Immunoreactivity in the axonal pathways was also found in the limbic-hypothalamic pathways, strionigral projection, and part of the corpus callosum. Results of Western blot analysis and 3H-InsP3 binding assay were consistent with the qualitative regional differences of immunoreactivity demonstrated by immunohistochemical study. The location of InsP3 receptor in the brain correlates well with the InsP3 binding sites demonstrated by an autoradiographic study.

Animals↗

[Evidence for sensory convergences in rat entorhinal cortex].

Unit neuronal activity was investigated in the Rat lateral entorhinal cortex. Neurons were found which reacted to various sensory stimulations, auditory, visual, somesthetic, gustative and olfactory. This cortex is thus a site of convergence of sensory information which could be relayed further to the hippocampus.

Animals↗

Adult-derived neural precursors transplanted into multiple regions in the adult brain.

Neural stem cells persist in the adult brain subventricular zone (SVZ). These cells generate a large number of new neurons that migrate to the olfactory bulb, where they complete their differentiation. Here, we transplanted cells carrying beta-galactosidase under the control of neuron-specific enolase promoter (NSE::LacZ) from the SVZ of adult mice into the striatum cortex and olfactory bulb, with or without an excitotoxin lesion. Between 2 and 8 weeks after transplantation, grafted cells were present in the recipient regions, but extensive migration and differentiation into mature neurons of grafted cells were only observed in the olfactory bulb. Clusters of graft-derived neuroblasts forming chain-like structures were observed within or close to the grated sites in the cortex and striatum; electron microscopy confirmed that graft-derived cells in the olfactory bulb and a small number in the striatum were neurons. Surprisingly, most of the cells expressing NSE::LacZ outside the olfactory bulb were astrocytes. We conclude that primary precursors from the SVZ migrate and differentiate effectively only within the environment of the olfactory bulb. Only limited survival and differentiation were observed in other brain regions studied.

Animals↗

Patterns of Fos expression in the amygdala and ventral perirhinal cortex induced by training in an olfactory fear conditioning paradigm.

The activation of amygdaloid nuclei, the ventral perirhinal cortex (vPRh), and several other brain areas in the rat during the acquisition and expression of olfactory fear conditioning was assessed through Fos immunocytochemistry in 3 separate experiments. The results of Experiment 1 suggest that olfactory and somatosensory inputs may functionally converge in the anterior region ot the medial nucleus (aMe). The results of Experiment 2 indicate that the aMe exhibited significantly greater Fos-like immunoreactivity (FLI) in subjects acquiring conditioned stimulus-unconditioned stimulus associations than in those presented with the same olfactory and somatosensory stimuli in a manner that precluded acquisition. The results of Experiment 3 indicate that the vPRh appeared to exhibit learning-related increases in FLI during the expression of previously acquired associations. Collectively, these data suggest that the aMe and vPRh may be critically involved in different aspects of olfactory fear conditioning.

Amygdala↗

Opiate and muscarinic ligand binding in five limbic areas after bilateral olfactory bulbectomy.

Bilateral olfactory bulbectomy (BBX) in mice leads to a variety of neutrochemical changes in 5 limbic areas associated with the bulbs. Within one week after BBX, opiate ligand binding declined by 73% in the amygdala, rose by 82% in the hypothalamus and then returned to sham levels by 4 weeks in both areas. Opiate binding also declined by 47% in the olfactory tubercle and to essentially zero in the piriform cortex and the olfactory peduncle after 16 weeks. Muscarinic cholinergic binding declined in the amygdala and hypothalamus at 16 weeks after BBX, but reductions in muscarinic binding were observed in the piriform cortex and the olfactory peduncle by two weeks postsurgery. Muscarinic binding in the olfactory tubercle was unaffected by BBX, as was binding of beta-adrenergic and benzodiazepine ligands in the limbic areas. Binding of [3H]spiroperidol rose 61% in the olfactory tubercle two weeks after surgery and then declined to normal levels. Choline acetyltransferase activity rose by 64% within one week after BBX in the piriform cortex and remained elevated throughout the study. Activity of this enzyme also rose in the olfactory peduncle and the olfactory tubercle after surgery. BBX had only moderate effects on glutamic acid decarboxylase in the limbic areas, and enzyme activity increased 25% in the olfactory tubercle and the piriform cortex 4 weeks after BBX. BBX also resulted in a moderate decrease (22%) in DOPA decarboxylase activity in the olfactory tubercle two weeks after BBX. The implications of these neurochemical changes are discussed in terms of what is known about bulb-limbic system connections.

Amygdala↗