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PubMed1994

Hybridization histochemical localization of activin receptor subtypes in rat brain, pituitary, ovary, and testis.

We have studied the distribution of activin receptor gene expression in the brain, pituitary, ovary, and testis of the adult rat by in situ hybridization, using probes complementary to the mRNAs encoding the mouse activin receptor subtypes II and IIB (ActRII and ActRIIB). Throughout the brain, ActRII mRNA expression was stronger than that of ActRIIB, and the patterns of expression were similar, although not identical. The most intense sites of activin receptor gene expression were the hippocampal formation, especially the dentate gyrus (ActRII), taenia tecta, and induseum griseum; the amygdala, particularly the amygdaloid-hippocampal transition zone; and throughout the cortical mantle, including the primary olfactory cortex (piriform cortex and olfactory tubercle); other regions of the cortex showing lesser degrees of hybridization included the cingulate cortex, claustrum, entorhinal cortex, and subiculum. In addition, moderate levels of expression were observed in several hypothalamic areas involved in neuroendocrine regulation, such as the suprachiasmatic, supraoptic, paraventricular, and arcuate nuclei. Moreover, activin receptors were also expressed in regions with inputs to the hypothalamus, both in the forebrain (bed nucleus of the stria terminalis and medial preoptic area) and within the brainstem (nucleus of the solitary tract, dorsal motor nucleus of the vagus, locus coeruleus, and mesencephalic raphé system). ActRII mRNA was observed in the intermediate lobe of the pituitary and, less prominently, in the anterior lobe, whereas ActRIIB appeared to be weakly expressed throughout all three pituitary divisions. In both male and female gonads, activin receptor message was clearly present in germ cells, and ActRII was the predominant form. In the ovary, in addition to an intense signal in the oocyte, activin receptor was expressed in corpus luteum and granulosa cells during diestrous day 1. In the testis, there was a strong ActRII signal in rounded spermatids, and a moderate signal in pachytene spermatocytes. In contrast, ActRIIB was absent within tubules, but weakly expressed in interstitial and Leydig cells. This is the first report of the distribution of activin receptor message in adult mammalian tissues. Although consistent with some previously suggested functional associations of activin-containing pathways in the brain, this pattern of expression suggests a greater role for activin than was previously appreciated in cortical, limbic, and somatosensory pathways and in the maturation of germ cells in the gonads of both male and female rats.

Activin Receptors↗
PubMed1991

Efferent projections of the infralimbic (area 25) region of the medial prefrontal cortex in the rat: an anterograde tracer PHA-L study.

The efferent projections of the infralimbic region (IL) of the medial prefrontal cortex of the rat were examined by using the anterograde transport of Phaseolus vulgaris leucoagglutinin (PHA-L). Major targets of the IL were found to include the agranular insular cortex, olfactory tubercle, perirhinal cortex, the whole amygdaloid complex, caudate putamen, accumbens nucleus, bed nucleus of the stria terminalis, midline thalamic nuclei, the lateral preoptic nucleus, paraventricular nucleus, supramammillary nucleus, medial mammillary nucleus, dorsal and posterior areas of the hypothalamus, ventral tegmental area, central gray, interpeduncular nucleus, dorsal raphe, lateral parabrachial nucleus and locus coeruleus. Previously unreported projections of the IL to the anterior olfactory nucleus, piriform cortex, anterior hypothalamic area and lateroanterior hypothalamic nucleus were observed. The density of labeled terminals was especially high in the agranular insular cortex, olfactory tubercle, medial division of the mediodorsal nucleus of the thalamus, dorsal hypothalamic area and the lateral division of the central amygdaloid nucleus. Several physiological and pharmacological studies have suggested that the IL functions as the 'visceral motor' cortex, involved in autonomic integration with behavioral and emotional events. The present investigation is the first comprehensive study of the IL efferent projections to support this concept.

Amygdala↗
PubMed1975

Local anesthetics and barbiturates: effects on evoked potentials in isolated mammalian cortex.

Slices of olfactory cortex from guinea pig, incorporating the lateral olfactory tract (LOT), were maintained in a glucose-bicarbonate solution in vitro. Stimulation of the LOT produced: 1) A summed LOT action potential; 2) A monosynaptic surface-negative wave (N-wave); and 3) A polysynaptic surface-positive wave (P-wave) as recorded from the pial surface of the slice at 24 degrees C. During a period of single stimulus pulses to the LOT, local anesthetics and barbiturates, applied to the incubating solution, depressed the amplitude of the action potential (while increasing its latency and threshold) with the following potencies: tetracaine greater than cocaine greater than lidocaine greater than procaine greater than pentobarbital greater than phenobarbital. The order of potencies was similar for the synaptic potentials. Each local anesthetic or bartiturate first depressed the P-wave, the N-wave and then the LOT potential, with all three potentials being affected within a narrow range of drug concentrations. There was a good linear relationship between drug potency on all potentials and the distribution coefficients of the drugs in octanol-water. During a period of double stimulus pulses to the LOT, up to 10 seconds apart, low concentrations of barbiturates depressed the N-wave to the second pulse with little effect on the first, conditioning pulse, an effect not seen with local anesthetics. The bath concentrations required for this effect of both barbiturates were similar to previous reports of blood concentrations required for general anesthesia. It appears that local anesthetics have actions on brain similar to those reported for other tissues and that barbiturates share some of the actions of local anesthetics, but exert a selective depression on repetitively elicited synaptic potentials.

Anesthetics, Local↗
PubMed1987

Anterograde transsynaptic transport of WGA-HRP in rat olfactory pathways.

The transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) was studied in rat olfactory pathways. After applications of tracer to the vomeronasal organ, the olfactory epithelium or injections into the olfactory bulb, WGA-HRP reaction product was observed in second-order neuron terminal areas of each pathway, e.g. within posteromedial cortical amygdaloid nucleus, primary olfactory cortex and contralateral primary olfactory cortex, respectively. The results indicate that anterograde transsynaptic transport of WGA-HRP occurs in olfactory pathways, as has been shown in visual, somatosensory and limbic systems, and thus, anterograde transsynaptic transport may be a mechanism for neurons to exchange materials and/or messages.

Animals↗
PubMed1985

Differences in some of the metabolic properties of mitochondria isolated from cerebral cortex and olfactory bulb of the rat.

The metabolic properties of mitochondria from rat cerebral cortex and olfactory bulb were investigated. The pyruvate-supported oxygen uptake rates by olfactory bulb mitochondria were significantly lower than those by cerebrocortical mitochondria. This is consistent with the differences in pyruvate dehydrogenase complex activities between these mitochondrial preparations. Pyruvate dehydrogenase kinase, NAD-linked isocitrate dehydrogenase, and hexokinase activities in olfactory bulb mitochondria were significantly lower than those in cerebrocortical mitochondria. However, NADP-linked isocitrate dehydrogenase, and NAD-linked and NADP-linked glutamate dehydrogenase activities in olfactory bulb mitochondria were significantly higher than those in cerebrocortical mitochondria. The differences between these two mitochondrial preparations in terms of the activities of these energy-metabolizing enzymes reflect the differences detected in the homogenates of these regions.

Animals↗
PubMed2002

The minimum number of neurons in the central olfactory pathway in relation to its function: a retrograde fiber tracing study.

The present study was aimed at determining the functionally essential size of the neuronal population in the central olfactory nervous system. Using conditioned rats who had learnt to avoid repellent (cycloheximide) solution by olfaction, varying degrees of injuries were made to the lateral olfactory tract, a major central olfactory pathway connecting the olfactory bulb to the olfactory cortex. After examining their olfactory ability to discriminate cycloheximide solution from water, intact bulbar projection neurons (mitral cells) with fiber connections to the olfactory cortex were quantified using a retrograde fiber tracing technique. The numbers of retrogradely labeled mitral cells from the rats with normal olfaction ranged between 20 and 92% of the control value, while those numbers from the anosmic rats ranged between 0 and 22%. We conclude that the functionally essential neuronal population is approximately one-fifth of the total in the central olfactory pathway, a presumed threshold value in terms of the ability to avoid cycloheximide solution by olfactory discrimination.

Animals↗
PubMed1995

Characterization of a human and murine gene (CLCN3) sharing similarities to voltage-gated chloride channels and to a yeast integral membrane protein.

We describe the isolation and characterization of a human gene (CLCN3) and its murine homologue (Clcn3) sharing significant sequence and structural similarities with all previously identified members of the voltage-gated chloride channel (ClC) family. This gene is expressed primarily in tissues derived from neuroectoderm. Within the brain, Clcn3 expression is particularly evident in the hippocampus, olfactory cortex, and olfactory bulb. CLCN3 encodes a 760-amino-acid protein that differs by only 2 amino acid residues from the protein encoded by Clcn3. CLCN3 protein also shows a high similarity with GEF1, an integral membrane protein of the yeast Saccharomyces cerevisiae known to be involved in respiration and iron-limited cell growth, and with the predicted protein product of a DNA sequence from the mold Septoria nodorum. This high degree of sequence conservation in very distantly related species such as human and yeast indicates that this gene has retained a fundamental function throughout evolution.

Amino Acid Sequence↗
PubMed1992

Localization of the tachykinin neurokinin B precursor peptide in rat brain by immunocytochemistry and in situ hybridization.

Tachykinins exert a broad range of actions in the mammalian nervous system. While much is known about the localization of peptides derived from one of the two mammalian tachykinin genes (substance P- and neurokinin A-encoding preprotachykinin), little has been reported on the localization of peptides derived from a second tachykinin gene encoding neurokinin B. Using an antiserum raised against a 30-residue peptide fragment (Peptide 2) of the protein precursor to neurokinin B, we have mapped the distribution of Peptide 2 by immunocytochemistry. Peptide 2 antiserum specificity was determined by western blot analysis (which showed antibody cross-reactivity to a neurokinin B fusion protein from a cloned neurokinin B-encoding complementary DNA) and by the elimination of immunoreactive product in brain tissue sections upon preabsorption with a 10 microM concentration of Peptide 2 peptide. In addition, we report on the distribution of neurokinin B-messenger RNA with a full-length complementary RNA probe to localize cells that express the neurokinin B precursor. Peptide 2 immunoreactivity and neurokinin B-messenger RNA-positive cells were found, in some instances, paralleling the distribution of substance P and in other cases existing separately from substance P. Peptide 2 immunoreactivity as well as neurokinin B-messenger RNA-positive cells were found in the main olfactory bulb, cortex, olfactory tubercle, nucleus accumbens, hippocampus, bed nucleus of the stria terminalis, amygdala, medial habenula, periaqueductal gray, superior and inferior colliculus, and nucleus of the spinal trigeminal tract. Whereas substance P is found throughout the rat brain, neurokinin B appears to be partitioned more to forebrain than to brainstem structures. The marked differences in the distribution of both tachykinins in the rat central nervous system suggests that neurokinin B may play an important role in olfactory, gustatory, visceral, and neuroendocrine processing of information.

Amino Acid Sequence↗
PubMed1993

The regional distribution of extracellularly regulated kinase-1 and -2 messenger RNA in the adult rat central nervous system.

It has previously been shown that an intracellular serine/threonine kinase known as extracellularly signal-regulated kinase, also known as microtubule-associated protein kinase, is phosphorylated and activated in response to a range of hormones, growth factors (e.g. nerve growth factor) and neurotransmitters (e.g. N-methyl-D-aspartate) in a variety of cells including neurons. Extracellularly regulated kinases phosphorylate transcription factors, cytoskeletal proteins and enzyme targets. As such they are believed to function in neuronal signal transduction. In situ hybridization histochemistry using synthetic oligonucleotide probes has been used to identify cells in the adult rat central nervous system containing messenger RNAs coding for two isoforms of extracellularly regulated kinase. Extracellularly regulated kinase-2 messenger RNA was observed in many regions including the cerebral cortex, olfactory bulb, hippocampus, amygdala, basal ganglia (except the globus pallidus and endopeduncular nucleus), basal nucleus, thalamus, hypothalamus, brain stem nuclei, cerebellum and neurons in the spinal cord. Extracellularly regulated kinase-1 messenger RNA was confined to fewer regions than extracellularly regulated kinase-2 messenger RNA. Hybridization signals for extracellularly regulated kinase-1 were seen in the olfactory bulb, cortex, regions of the hippocampus, amygdala, nucleus basalis of Maynert, substantia nigra, some hypothalamic and brainstem nuclei and cerebellum, as well as neurons of the spinal cord. Of particular interest, extracellularly regulated kinase-1 messenger RNA was absent from all regions of the basal ganglia and thalamus. Furthermore, extracellularly regulated kinase-1 was almost absent from the CA1 region, whereas extracellularly regulated kinase-2 was present in all neurons of the hippocampus. There were no CNS regions that expressed extracellularly regulated kinase-1 but not extracellularly regulated kinase-2; however, neurons of the dorsal root ganglia showed extracellularly regulated kinase-1 but not extracellularly regulated kinase-2 messenger RNA. Although extracellularly regulated kinase-1 and extracellularly regulated kinase-2 expression was selectively neuronal in the brain, extracellularly regulated kinase-1 messenger RNA was localized to glia in the spinal cord. The distinct cellular distribution of individual extracellularly regulated kinases in the adult rat CNS suggests that they play unique signalling roles.

Animals↗
PubMed2003

The evolutionary origin of the mammalian isocortex: towards an integrated developmental and functional approach.

The isocortex is a distinctive feature of mammalian brains, which has no clear counterpart in the cerebral hemispheres of other amniotes. This paper speculates on the evolutionary processes giving rise to the isocortex. As a first step, we intend to identify what structure may be ancestral to the isocortex in the reptilian brain. Then, it is necessary to account for the transformations (developmental, connectional, and functional) of this ancestral structure, which resulted in the origin of the isocortex. One long-held perspective argues that part of the isocortex derives from the ventral pallium of reptiles, whereas another view proposes that the isocortex originated mostly from the dorsal pallium. We consider that, at this point, evidence tends to favor correspondence of the isocortex with the dorsal cortex of reptiles. In any case, the isocortex may have originated partly as a consequence of an overall "dorsalizing" effect (that is, an expansion of the territories expressing dorsal-specific genes) during pallial development. Furthermore, expansion of the dorsal pallium may have been driven by selective pressures favoring the development of associative networks between the dorsal cortex, the olfactory cortex, and the hippocampus, which participated in spatial or episodic memory in the early mammals. In this context, sensory projections that in reptiles end in the ventral pallium, are observed to terminate in the isocortex (dorsal pallium) of mammals, perhaps owing to their participation in these associative networks.

Anatomy, Comparative↗
PubMed1983

Dual olfactory representation in the rat thalamus: an anatomical and electrophysiological study.

A combination of electrophysiological and anatomical techniques was used to determine the sites of termination of olfactory projections to the thalamus and the distribution of the cells of origin of these projections within the olfactory cortex. Following electrical stimulation of the olfactory bulb, short-latency unit responses were recorded not only in the central segment of the mediodorsal thalamic nucleus but also in the ventral and anterior parts of the submedial thalamic nucleus. Responses were not obtained in the ventral or lateral parts of the mediodorsal nucleus, in the dorsal part of the submedial nucleus, or in the intralaminar nuclei between the mediodorsal and submedial nuclei. The cells of origin of the projection were identified by making injections of horseradish peroxidase conjugated to wheat germ agglutinin (HRP WGA) into the thalamus and examining the olfactory cortex for retrogradely labeled cells. Following injections into the mediodorsal nucleus, labeled cells were found in the polymorphic cell zone deep to the olfactory tubercle, in the ventral endopiriform nucleus deep to the piriform cortex, and in an equivalent position deep to the periamygdaloid and lateral entorhinal cortices. After injections into the submedial nucleus, a smaller number of labeled cells were found in similar locations, except that they were restricted to the rostral olfactory cortical areas and were not found deep to the lateral part of the piriform cortex. Retrogradely labeled cells and anterogradely labeled axons were also found in the lateral orbital and ventral agranular insular areas of the prefrontal cortex with injections into the mediodorsal nucleus, and in the ventrolateral orbital area with injections into the submedial nucleus. Anterograde tracing experiments, using the autoradiographic method, have confirmed these results. Injections of 3H-leucine deep to the junction between the anterior piriform cortex and the olfactory tubercle label axons in both the central segment of the mediodorsal nucleus and the ventral part of the submedial nucleus, while injections deep to the posterior piriform cortex label axons in the mediodorsal nucleus only. Within the mediodorsal nucleus, the projection also appears to be organized so that fibers which arise more rostrally terminate ventrolaterally in the central segment, while fibers which arise more caudally terminate more dorsomedially. These results indicate that there is a substantial and possibly dual thalamocortical mechanism available for processing of olfactory stimuli.

Animals↗
PubMed1980

Adenylate cyclase in the developing rat cerebral cortex and olfactory bulb.

Activities of adenylate cyclase, measured either in the absence or presence of sodium fluoride and Triton X-100, are determined in cerebral cortex and olfactory bulb homogenate of rats of 1 to 35 days of postnatal age. Differences in properties of the enzyme in the 2 structures are demonstrated.

Adenylyl Cyclases↗
PubMed1975

A normally laminated afferent projection to an abnormally laminated cortex: some olfactory connections in the reeler mouse.

The relative positions of pyramidal and polymorphic cell classes are inverted in the central olfactory cortical structures of the reeler mutant mouse. Each cell class is generated at the normal embryonic time. The polymorphic cells of the mutant, like those of the normal, are generated between E11-E13. The pyramidal cells are formed between E11-E16 in both. Despite the anomalous positions of their somata deep in the cortex the apical dendrites of many pyramidal cells reach and ramify at a superficial cortical level subjacent to the lateral olfactory tract. The main and accessory olfactory bulbs are cytoarchitectonically normal in the mutant and project normally upon the anterior olfactory nucleus, the olfactory tubercle, the hippocampal rudiment, the piriform cortex, the amygdaloid region and the entorhinal cortex. As in the normal animal the axons transverse layer Ialpha, and their terminals are concentrated in the immediately subjacent laminar zone. The rostrally directed cortic-cortical association system of the piriform cortex projects upon the anterior olfactory nucleus in the mutant just as in the normal with a relative concentration of terminals in a lamina subjacent and complementary to the zone of termination afferent systems in the abnormally laminated olfactory cortex of the mutant syggests that, in this system at least, the developmental mechanisms which determine relative position of neuron somata and those which govern axon trajectories and the distribution of axon terminals are largely independent.

Animals↗
PubMed1991

Asymmetric sigmoid non-linearity in the rat olfactory system.

The statistical relationship between multi-unit spike activity and simultaneously recorded local dendritic field potentials in the olfactory system of the waking rat was studied with chronically placed electrodes. The relationship had the form of a sigmoid increase in axonal firing probability conditional on the amplitude of dendritic potentials. These data were fitted with an asymmetric sigmoid curve previously derived from the Hodgkin-Huxley equations. The curve was fitted using non-linear regression to optimize its parameter: the maximal firing rate. The maximal rate also gave the steepness of the slope of the sigmoid. Pulse trains were recorded from excitatory and inhibitory neurons in the olfactory cortex (including the anterior olfactory nucleus, the prepyriform cortex and the lateral entorhinal area) as identified by the phase relations of the pulse probability and the dendritic potentials, and from the excitatory neurons in the bulb (the inhibitory granule cells do not give extracellularly detectable action potentials). All these neurons are known to interact in disynaptic negative feedback loops giving rise to oscillations. The same sigmoid function fit the data from both types of neurons in all locations. The curves for neurons in all parts of the olfactory cortex had a 3-fold higher slope and maximal value than the curves from bulbar neurons. The significances of this difference and of the asymmetric sigmoid are discussed in terms of models for olfactory oscillatory dynamics and pattern recognition.

Anesthesia↗
PubMed1998

Manganese transport in the neural circuit of rat CNS.

To study manganese (Mn) transport in the neural circuit of rat CNS, brain isotope distribution after 54Mn injection into the brain was analyzed by autoradiography. One day after 54MnCl2 injection into the striatum, 54Mn was highly distributed in the ipsilateral thalamus, hypothalamus, and substantia nigra. When 54MnCl2 was bilaterally injected into the striata after unilateral treatment with colchicine or vehicle into the medial forebrain bundle, 54Mn was distributed in both sides of the substantia nigra of vehicle-treated rats. On the other hand, unilateral colchicine treatment caused a decrease of 54Mn distribution in the ipsilateral substantia nigra, suggesting that Mn is subjected to axonal transport in the striatonigra and/or nigrostriatal pathways. In the case of unilateral injection of 54MnCl2 into the olfactory bulb, 54Mn was distributed in the ipsilateral piriform, amygdaloid areas (the primary olfactory cortex), and entorhinal area (the secondary olfactory cortex). These results suggest that Mn is subject to widespread axonal transport in the neural circuits. Moreover, Mn may be taken up by the piriform neurons (the third olfactory neuron) after release from the secondary olfactory neuron terminals and transported to the entorhinal area.

Animals↗
PubMed1983

The topographic organization of associational fibers of the olfactory system in the rat, including centrifugal fibers to the olfactory bulb.

This study analyzed the topographic organization of the associational fibers within the olfactory cortex of the rat, by using the autoradiographic method. Small injections of 3H-leucine were placed in all of the subdivisions of the olfactory cortex, to label selectively the fibers arising in each area. Intracortical fibers were identified from all of the olfactory cortical areas except the olfactory tubercle and were classified into two major systems (the layer Ib system and the layer II-deep Ib system) on the basis of their laminar pattern of termination (see Luskin and Price, '83). The layer Ib fiber system arises in the anterior olfactory nucleus, piriform cortex, and lateral entorhinal area, and is broadly organized in relation to the lateral olfactory tract. Cortical areas deep to or near the lateral olfactory tract are preferentially interconnected with areas near the tract, while parts of the cortex lateral and caudal to the lateral olfactory tract are most heavily interconnected with areas lateral, caudal, and medial to the tract. Commissural projections from the anterior olfactory nucleus and the anterior piriform cortex match some (but not all) components of the ipsilateral layer Ib fiber system. The layer II-deep Ib fiber system arises in three small areas--the ventral tenia tecta, the dorsal peduncular cortex, and the periamygdaloid cortex. The fibers from the ventral tenia tecta terminate in layer II of the anterior olfactory nucleus and are topographically organized. The fibers from the dorsal peduncular cortex and the periamygdaloid cortex are more widely distributed, especially in the lateral and caudal parts of the cortex. Two other intracortical projections do not fit into either of these fiber systems. The nucleus of the lateral olfactory tract projects bilaterally to the islands of Calleja and the medial edge of the anterior piriform cortex. The anterior cortical nucleus projects to many parts of the olfactory cortex, but the fibers end in both superficial and deep parts of layer I (layer Ia and Ib). There are projections from several of the olfactory cortical areas to the cortical areas surrounding the olfactory cortex. Virtually all of the olfactory areas also project to the ventral and dorsal endopiriform nuclei deep to the piriform cortex and/or to the polymorph zone deep to the olfactory tubercle. In addition, projections have been demonstrated to the deep amygdaloid nuclei, especially from the more ventromedial and caudal parts of the olfactory cortex.

Amygdala↗
PubMed1984

The development of axonal connections in the central olfactory system of rats.

The development of the cytoarchitecture and axonal connections of the central olfactory system were studied in fetal and neonatal rats from E16. In contrast to neocortical development, the olfactory cortex lacks a distinct cortical plate. In the piriform cortex and the olfactory tubercle the cellular laminae emerge simultaneously, while in the anterior olfactory nucleus, there are morphogenetic gradients from superficial to deep as well as from caudal to rostral which parallel the known cytogenetic gradients. Parallel morphogenetic and cytogenetic gradients are also present in the lateral to medial axis of the olfactory tubercle. The projection from the olfactory bulb and the associational projections from the piriform cortex begin to develop well before birth. At E17 fibers from the bulb are limited to the lateral olfactory tract (LOT) and the molecular layer just deep to it, and then spread out caudally, laterally, and medially away from the LOT. This sequence of innervation parallels and predicts the density of innervation in the adult: those areas which are innervated first (such as the piriform cortex deep to the LOT) ultimately receive the heaviest innervation; conversely, those areas which are innervated very late (such as the medial olfactory tubercle) receive the lightest projection. The intracortical projections from the anterior and posterior piriform cortex extend into layer I ipsilaterally by E20 and obtain their adult distribution by the middle of the first postnatal week. On the other hand, fibers from the anterior olfactory nucleus and the entorhinal area do not reach their full adult extent until the second postnatal week. Similarly, the crossed projection of the anterior piriform cortex to the contralateral posterior piriform cortex does not grow into layer I until this later time. The timing of fiber ingrowth showed no relation to the trajectory or eventual areal or laminar termination of fibers. As with the olfactory bulb projection, the timing may influence the density of termination. Centrifugal fibers to the bulb are demonstrable around the time of birth both by the retrograde transport of horseradish peroxidase (HRP) and by the anterograde transport of 3H-leucine. The arrival of additional fibers during the remainder of the first postnatal week parallels the known cytogenetic and morphogenetic gradients in the areas in which they arise. The projections of the olfactory cortex to the lateral hypothalamic area and the mediodorsal thalamic nucleus are evident before birth. This correlates with the early generation of the cells which give rise to these projections.

Aging↗
PubMed1994

Antidepressant-induced modulation of GABAA receptors and beta-adrenoceptors but not GABAB receptors in the frontal cortex of olfactory bulbectomised rats.

The effects of prolonged administration of antidepressant drugs, belonging to three different classes, on high-affinity GABAA receptor, GABAB receptor and beta-adrenoceptor binding parameters were determined in the frontal cortex of olfactory bulbectomised rats. Clorgyline (1 mg/kg/day), paroxetine (10 mg/kg/day) or desipramine (10 mg/kg/day) were administered for 21 days via subcutaneous osmotic minipumps implanted in the scapular region 7 days after bulbectomy. Cortical GABAA receptor densities, defined with [3H]gamma-aminobutyric acid ([3H]GABA), were significantly increased following bulbectomy. This effect on Bmax values was reversed by all three antidepressant drugs. GABAB receptor densities decreased slightly after bulbectomy. Chronic antidepressant administration had no effect on GABAB receptor binding parameters. Olfactory bulbectomy did not induce any changes in cortical beta-adrenoceptor binding parameters determined with [3H]CGP-12177 ((-)-4-(3-t- butylamino-2-hydroxypropxy)- [5,7-3H]benzimidazol-2-one). However, prolonged administration of all three antidepressant drugs induced a downregulation of beta-adrenoceptors. The results of the present study confirm the involvement of cortical GABAA rather than GABAB receptors in the olfactory bulbectomy animal model of human depression. Moreover, the data further support the hypothesis that a decrease in function of the GABAA receptor complex could play a role in the therapeutic effects of antidepressant treatments.

Adrenergic beta-Antagonists↗