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PubMed2005

Hodological characterization of the septum in anuran amphibians: II. Efferent connections.

The efferent connections of the septum of the gray treefrog Hyla versicolor were studied by combining anterograde and retrograde tracing with biotin ethylendiamine (Neurobiotin). The lateral septal complex projects mainly to the medial pallium, limbic regions (e.g., amygdala and nucleus accumbens), and hypothalamic areas but also to sensory nuclei in the diencephalon and midbrain. The central septal complex strongly innervates the medial pallium, limbic, and hypothalamic areas but also specific sensory (including olfactory) regions. The medial septal complex sends major projections to all olfactory nuclei and a weaker projection to the hypothalamus. Our results indicate that all septal nuclei may modify the animal's internal state via efferents to limbic and hypothalamic areas. Via projections to the medial pallium, lateral and central septal complexes may be involved in learning processes as well. Because of their connections to specific sensory areas, all septal areas are in a position to influence sensory processing. Furthermore, our data suggest that both the postolfactory eminence and the bed nucleus of the pallial commissure are not part of the septal complex, rather, the postolfactory eminence seems to be comparable to the mammalian primary olfactory cortex, whereas the bed nucleus may be analogous to the mammalian subfornical organ.

Animals↗
PubMed1987

Sources of presumptive glutamergic/aspartergic afferents to the rat ventral striatopallidal region.

The distribution of presumptive glutamergic and/or aspartergic neurons retrogradely labeled following injections of 3H-D-aspartate (3H-D-Asp) into the ventral striatopallidal region was compared with the distribution of neurons labeled by comparable injections of wheat germ agglutinin-horseradish peroxidase (WGA-HRP). The afferents labeled by 3H-D-Asp were a subset of those labeled by WGA-HRP. The major sources of afferents to the nucleus accumbens and olfactory tubercle that could be labeled by 3H-D-Asp were in the medial frontal and insular cortices; the olfactory cortex; the lateral, basolateral, and basomedial amygdaloid nuclei; and the midline nuclear complex of the thalamus. The corresponding afferents to the ventral pallidum arose in the central, medial, and basomedial amygdaloid nuclei and the midline thalamic nuclei. In addition, the nucleus of the lateral olfactory tract was moderately or heavily labeled by 3H-D-Asp injections into all three areas, and cells were labeled in the subiculum following injection in the anteromedial part of the nucleus accumbens. Conversely the ventral striatopallidal structures themselves were, at best, sparsely labeled by any of the 3H-D-Asp injections. Neurons in the substantia nigra, ventral tegmental area, dorsal raphe, and locus coeruleus were labeled by WGA-HRP but not by 3H-D-Asp, except for an occasional cell in the raphe. The results indicate that 3H-D-Asp is a specific retrograde tracer and suggest that there are widespread, presumably excitatory, glutamergic and/or aspartergic inputs to the ventral striatum and pallidum.

Animals↗
PubMed2005

Beyond the olfactory bulb: an odotopic map in the forebrain.

We report electrophysiological evidence that a simple odotopy, the spatial mapping of different odorants, is maintained above the level of the olfactory bulb (OB). Three classes of biologically relevant odorants for fish are processed in distinct regions of the forebrain (FB) in the channel catfish. Feeding cues, mainly amino acids and nucleotides, are represented in lateral, pallial portions of the FB, equivalent to the olfactory cortex of amniote vertebrates, whereas social signals mediated by bile salts are represented in medial FB centers, possibly homologous to portions of the amygdala. As in the OB, the different odorant classes map onto different territories; however, the response properties of units of the olfactory areas of the FB do not simply mirror those of the OB. For some units, distinctive response properties emerged, because the FB is the first center where odors subserving a common behavioral function (i.e., food function) converge.

Animals↗
PubMed1999

A genetic approach to trace neural circuits.

Mammalian nervous system function involves billions of neurons which are interconnected in a multitude of neural circuits. Here we describe a genetic approach to chart neural circuits. By using an olfactory-specific promoter, we selectively expressed barley lectin in sensory neurons in the olfactory epithelium and vomeronasal organ of transgenic mice. The lectin was transported through the axons of those neurons to the olfactory bulb, transferred to the bulb neurons with which they synapse, and transported through the axons of bulb neurons to the olfactory cortex. The lectin also was retrogradely transported from the bulb to neuromodulatory brain areas. No evidence could be obtained for adverse effects of the lectin on odorant receptor gene expression, sensory axon targeting in the bulb, or the generation or transmission of signals by olfactory sensory neurons. Transneuronal transfer was detected prenatally in the odor-sensing pathway, but only postnatally in the pheromone-sensing pathway, suggesting that odors, but not pheromones, may be sensed in utero. Our studies demonstrate that a plant lectin can serve as a transneuronal tracer when its expression is genetically targeted to a subset of neurons. This technology can potentially be applied to a variety of vertebrate and invertebrate neural systems and may be particularly valuable for mapping connections formed by small subsets of neurons and for studying the development of connectivity as it occurs in utero.

Animals↗
PubMed2001

Cerebral hemodynamic response to unpleasant odors in the preterm newborn measured by near-infrared spectroscopy.

Newborn infants in intensive care units are exposed to several unfamiliar smells, mostly related to the nosocomial environment. How the preterm baby perceives these olfactory stimulations remains unclear. Near-infrared spectroscopy can be performed noninvasively above the olfactory cortex to monitor changes of cerebral blood flow as an indicator of cortical activation. The aim of this study was to explore by near-infrared spectroscopy how odorous substances routinely used in the neonatal intensive care unit influence bilateral cortical hemodynamics in the olfactory region of the brains of preterm infants. Specifically, a detergent (Neomidil) and an adhesive remover (Remove) have been tested. Twenty preterm neonates of gestational age 30-37 wk (mean 33.7 +/- 2.3 SD) and postconceptional age 32-37.3 wk (mean 35.5 +/- 2.75 SD) were monitored by near-infrared spectroscopy. Two optode pairs were placed above the anterior orbitofrontal gyri, which is involved in olfactory processing, on each side of the skull. Fifteen babies were exposed to the smell of a disinfectant and five babies to that of a detergent, both applied to small cotton pads. Changes of oxygenated Hb and deoxygenated Hb were recorded before, during, and after a 10-s stimulus. In 17 out of 20 babies, there was a decrease in oxygenated Hb and total Hb after the exposure to the substances. The decrease was significantly greater in the right side than in the left side. This change was different from that observed in our previous study after exposure to colostrum and the pleasant smell of vanilla, which elicited an increase in blood oxygenation in the same region. The biologic significance of this finding is unknown. We conclude that cortical hemodynamic modifications occur in the preterm newborn after exposure to preparations commonly used in the neonatal intensive care unit. A lateralization seems to occur in processing unpleasant olfactory cues.

Cerebrovascular Circulation↗
PubMedDate not supplied

Effects of non-synaptic neuronal interaction in cortex on synchronization and learning.

During neural communication by means of action potentials, small electromagnetic (EM) fields are also generated. We use a three layered cortical neural network model to study the effects of EM fields and gap junctions on spatio-temporal network activity. We investigate the possible role of these effects in synchronizing activity, a phenomenon which has been observed in the olfactory cortex and the hippocampus. The simulation results support the notion that fast synchronization of activity in distant parts of the neural network are made possible by means of EM fields and/or gap junctions. The results also indicate that these effects, to a certain extent, are beneficial to system performance.

Action Potentials↗
PubMed2003

Distribution of NTS3 receptor/sortilin mRNA and protein in the rat central nervous system.

The neurotensin (NT) receptor, NTS3, originally identified as the intracellular sorting protein sortilin, is a member of a recently discovered family of receptors characterized by a single transmembrane domain. The present study provides the first comprehensive description of the distribution of NTS3/sortilin mRNA and protein in adult rat brain using in situ hybridization and immunocytochemistry. Both NTS3/sortilin mRNA and immunoreactivity displayed a widespread distribution throughout the brain. High levels of NTS3/sortilin expression and immunoreactivity were found in neuronal cell bodies and dendrites of allocortical areas such as the piriform cortex and hippocampus. Regions expressing both high levels of NTS3/sortilin mRNA and protein also included several neocortical areas, the islands of Calleja, medial and lateral septal nuclei, amygdaloid nuclei, thalamic nuclei, the supraoptic nucleus, the substantia nigra, and the Purkinje cell layer of the cerebellar cortex. In the brainstem, all cranial nerve motor nuclei were strongly labeled. NTS3/sortilin mRNA and immunoreactivity were also detected over oligodendrocytes in major fiber tracts. Subcellularly, NTS3/sortilin was predominantly concentrated over intracytoplasmic membrane-bound organelles. Many of the areas exhibiting high levels of NTS3/sortilin (e.g., olfactory cortex, medial septum, and periaqueductal gray) have been documented to contain high concentrations of NT nerve cell bodies and axons, supporting the concept that NTS3/sortilin may play a role in NT sorting and/or signaling. Other areas (e.g., hippocampal CA fields, cerebellar cortex, and cranial nerve motor nuclei), however, are NT-negative, suggesting that NTS3/sortilin also exerts functions unrelated to NT signaling.

Adaptor Proteins, Vesicular Transport↗
PubMed1986

Excitatory neurotransmission within substantia nigra pars reticulata regulates threshold for seizures produced by pilocarpine in rats: effects of intranigral 2-amino-7-phosphonoheptanoate and N-methyl-D-aspartate.

Seizures produced by pilocarpine given i.p. to rats provide an animal model for studying the initiation, spread and generalisation of convulsive activity within the forebrain. Pilocarpine, 380 mg/kg, produces a sequence of behavioural and electroencephalographic alterations indicative of motor limbic seizures and status epilepticus, which is followed by widespread damage to the limbic forebrain resembling that occurring subsequent to prolonged intractable seizures. Microinjections of a selective antagonist at the N-methyl-D-aspartate receptor, (+/-)-2-amino-7-phosphonoheptanoate, into the substantia nigra pars reticulata, bilaterally, protects against the behavioural, electrographic and morphological features of seizures produced by pilocarpine, 380 mg/kg, with an ED50 of 0.0007 mumol (0.0004-0.0011). Microinjections of (+/-)-2-amino-7-phosphonoheptanoate, 0.005 or 0.01 mumol, into the substantia nigra pars compacta or into the dorsal part of mid-anterior striatum do not modify the electrographic and morphological sequelae of pilocarpine, 380 mg/kg. In rats pretreated with microinjections of N-methyl-D-aspartate into the substantia nigra pars reticulata, a non-convulsive dose of pilocarpine, 100 mg/kg, results in recurrent motor limbic seizures and status epilepticus. The ED50 of N-methyl-D-aspartate for the generation of seizures after pilocarpine, 100 mg/kg, is 0.0014 mumol (0.001-0.0019). Electrographic monitoring shows a pattern and sequence of evolution of convulsant activity within the hippocampus and cortex similar to that produced with pilocarpine, 380 mg/kg, alone. Morphological examination of brains from rats treated with N-methyl-D-aspartate in the substantia nigra pars reticulata and subsequently given pilocarpine, 100 mg/kg, which underwent status epilepticus, reveals widespread damage to the amygdala, thalamus, olfactory cortex, substantia nigra, neocortex, and hippocampus. Microinjections of N-methyl-D-aspartate, 0.002 mumol, into either the substantia nigra pars compacta or dorsal striatum, bilaterally, do not augment seizures produced by pilocarpine, 100 mg/kg. The results indicate that the threshold for pilocarpine-induced seizures in rats is modulated by excitatory amino acid neurotransmission within the substantia nigra pars reticulata.

2-Amino-5-phosphonovalerate↗
PubMed1985

Atrial natriuretic polypeptide: topographical distribution in the rat brain by radioimmunoassay and immunohistochemistry.

The widespread distribution of neurons containing alpha-atrial natriuretic polypeptide-like immunoreactivity in the rat brain was demonstrated using radioimmunoassay and immunohistochemistry in conjunction with specific antisera. The highest concentrations of alpha-atrial natriuretic polypeptide-like immunoreactivity were in the hypothalamus and septum, with low but still appreciable concentrations in the mesencephalon, cerebral cortex, olfactory bulb and thalamus by radioimmunoassay. Immunohistochemical studies clearly showed that the perikarya of immunoreactive neurons are most prevalent in the ventral part of the lateral septal nucleus, periventricular preoptic nucleus, bed nucleus of the stria terminalis, periventricular and dorsal parts of the paraventricular hypothalamic nucleus, ventromedial nucleus, dorsomedial nucleus, arcuate nucleus, median mamillary nucleus, supramamillary nucleus, zona incerta, medial habenular nucleus and the periaqueductal grey matter. Scattered neurons were seen in the cingulate cortex, endopiriform nucleus, lateral hypothalamic area, and pretectal and dorsal thalamic areas. In addition to the areas mentioned above, high concentrations of immunoreactive varicose fibers were seen in the glomerular layer of the olfactory bulb, external layer of the median eminence, central to paramedian parts of the interpeduncular nucleus and the paraventricular hypothalamic nucleus. The globus pallidus, medial and central amygdaloid nuclei, dorsal raphe, dorsal parabrachial nucleus, locus coeruleus, vagal dorsal motor nucleus, solitary nucleus and some circumventricular organs, including the subfornical organ and organum vasculosum laminae terminalis, contained considerable numbers of immunoreactive varicose fibers. In dehydrated rats and homozygous Brattleboro rats, the pattern of alpha-atrial natriuretic polypeptide-immunoreactive neurons and varicose fibers was qualitatively similar to that seen in normal conditioned rats. This study gives an atlas of the distribution of the alpha-atrial natriuretic polypeptide-containing neuronal system in the rat brain and provides the groundwork for studying the influence of this new peptide on various brain functions.

Animals↗
PubMed1986

Neurogenesis in the anterior olfactory nucleus and its associated transition areas in the rat brain.

Neurogenesis in the rat olfactory peduncle was examined with [3H]thymidine autoradiography. Animals in the prenatal groups were the offspring of pregnant females given an injection of [3H]thymidine on two consecutive gestation days. Nine groups of embryos were exposed to [3H]thymidine on embryonic days (E) E13-E14, E14-E15,...E21-E22, respectively. One group of postnatal animals was given four consecutive injections of [3H]thymidine on postnatal days (P) P0-P3. On P60, the percentage of labeled cells and the proportion of cells originating during either 24 or 48 hr periods were quantified at seven anatomical levels through both the anterior olfactory nucleus and the transition areas. A caudal (older) to rostral (younger) neurogenetic gradient is found both within and between structures in the olfactory peduncle. Neurons in the dorsal, lateral, and ventral-lateral transition areas are generated mainly between E14 and E19, those in the anterior olfactory nucleus mainly between E15 and E21. Only 3-4% of the neurons in the most anterior pars lateralis and pars dorsalis originate after birth. All parts of the anterior olfactory nucleus show a strong superficial (older) to deep (younger) neurogenetic gradient (the 'outside-in' pattern). In contrast, neurons in the ventral-lateral transition area and in the dorsal transition area originate in a deep to superficial neurogenetic gradient (the 'inside-out' pattern), suggesting that these areas are, in reality, primary olfactory cortex. The lateral transition area is truly 'transitional', showing no neurogenetic gradient along the superficial-deep plane. The medial transition area originates between E15 and E19 in a center (older) to edge (younger) 'sandwich' neurogenetic gradient along the rostrocaudal plane, a pattern apparently unrelated to neurogenetic gradients in other olfactory peduncle structures. These data suggest that characteristic patterns of neurogenesis, namely the 'inside-out' vs the 'outside-in' gradients, permit the assignment of different structures to cortical vs ganglionic cytoarchitectonic components of the olfactory relay system.

Animals↗
PubMed2003

Invasion and persistence of the neuroadapted influenza virus A/WSN/33 in the mouse olfactory system.

Invasion and persistence of the neuroadapted influenza virus A/WSN/33 in the mouse olfactory system was studied. WSN/33 instilled intranasally infected neurons in the olfactory epithelium and was transported in axons to the olfactory bulbs in wild type mice that survived the infection. In adult mice lacking the recombination activating gene 1 (RAG-1-/-), infected neurons occurred in the olfactory bulbs for 22-65 days after which the mice developed a rapidly progressive lethal infection affecting neurons in olfactory projection pathways, i.e. primary olfactory cortex, raphe in upper brainstem and hypothalamus. Adult mice without genes for interferon (IFN)-alpha/beta receptor, IFN-gamma receptor, inducible nitric oxide synthase (iNOS), IgH, the transporter associated with antigen processing 1 (TAP1), and natural killer cell-depleted mice, all survived the infection. Viral RNA was found in the olfactory bulbs in more than 80 per cent of the surviving iNOS-/-, IFN-gamma receptor-/-, and TAP1-/- mice. Taken together, this study shows that influenza A virus can invade the brain through the olfactory pathways and that the cellular immune responses prevent establishment of persistent infections in the olfactory bulbs. Furthermore, innate responses in olfactory bulbs may for a period of time keep the infection under control.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Deeply located granule cells and mitral cells undergo apoptosis after transection of the central connections of the main olfactory bulb in the adult rat.

The main olfactory bulb (MOB) is the first relay station of the olfactory system: it receives afferents from sensory neurons and sends efferents to the primary olfactory cortex. The MOB also receives many centrifugal afferents from various regions. Transection of peripheral afferents to the MOB has been reported to induce cell death in granule cells. However, little is known about the effect of transection of these central connections of the MOB in adult rats. Here, we used a unilateral olfactory peduncle transection model in the adult rat to examine neuronal degeneration in the MOB. In the MOB ipsilateral to the surgery, the granule cell layer (GCL) was smaller, and the number of mitral cells was decreased compared with the contralateral MOB at 7 days after surgery. Many degenerating cells were present in both the mitral cell layer (MCL) and GCL in the ipsilateral MOB at 3 days after surgery, although there were no obvious changes in the gross morphology. We also found terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end labeling (TUNEL)-positive cells in the MCL and GCL in the ipsilateral MOB at 3 days after surgery. The majority of the degenerating and TUNEL-positive cells were located in the deep, rather than the superficial, GCL. Immunohistochemistry for activated caspase-9 further supported the occurrence of apoptotic cell death in the mitral and deeply located granule cells. These results indicate that not only axotomized mitral cells, but also deeply located granule cells that were not directly injured, underwent apoptosis after transection of the central connections, and suggest that sensitivities to transection of the central connections differ among granule cells according to their depth in the GCL.

Animals↗
PubMed1997

Destruction of olfactory inputs affects the morphogenesis of the telencephalon in rats.

We unilaterally destroyed the nasal radix of rat embryos on day 15.5 of gestation (E15.5) in utero so as to block the olfactory inputs to the ipsilateral forebrain vesicle. The embryonic brains were examined after 6 days' survival (E21.5). In the deafferented half of the brain, LHRH neurons were significantly reduced in number, indicating the successful blocking of the olfactory input. On the deafferented side, the olfactory bulb failed to develop, and the telencephalic hemisphere, small in size, accompanied various histogenetic retardations in the primary olfactory cortex, in the cortical plate, and in the hippocampal formation. The striatum revealed remarkable structural differences between the ipsilateral and contralateral sides: on the ipsilateral side, the striatum was small in size and displayed numerical reductions of immunoreactive tyrosine hydroxylase (TH) fibers and substance P (SP) neurons in comparison with those in the contralateral one; in the substantia nigra, TH neurons and SP fibers were less numerous on the deafferented side. There were no remarkable differences in the distribution of TH neurons in the hypothalamus. In view of these sequential histogenetic alterations, it can be assumed that the olfactory inputs play a key role in the telencephalic morphogenesis.

Amygdala↗
PubMed2004

Isolated congenital anosmia with morphologically normal olfactory bulb in two Iranian families: a new clinical entity?

Congenital total loss of the sense of smell occurs as a part of a syndrome or isolated anosmia. Kallmann syndrome is the most well known congenital anosmia associated with hypogonadotropic hypogonadism. Isolated congenital anosmia (ICA) is a very rare condition and appears to be due to changes in the olfactory epithelium or to aplasia of the olfactory nerve, bulb, and tract. Here we report two unrelated Iranian families with ICA. One family consisted of nine affected members, and the other family contained three affected members. Clinical history, physical examination, and smell testing by intravenous injection of combined vitamins (Alinamin trade mark, Takeda Pharmaceutical Co. Ltd., Japan) confirmed the disease in each affected member. No signs of hypogonadism or other neurological disorders were observed in any affected members. Family analysis with the complete ascertainment method under assumption of the same condition in the two families suggested that the disease is not inconsistent with an autosomal dominant mode with incomplete penetrance. The inheritance in one family appears unusual, i.e., there were no affected individuals in the third generation. When only two upper generations in the family are concerned, the segregation ratio was 0.39 +/- 0.11. Male-to-male transmissions were observed and both sexes were affected in both families. Magnetic resonance imaging (MRI) of the olfactory bulb and sulcus revealed no evidence of morphological changes in all affected members, suggesting that these patients have either a defect in the olfactory epithelium or a functional defect in the olfactory cortex.

Female↗
PubMed1985

Inhibitory influence of GABA on central serotonergic transmission. Raphé nuclei as the neuroanatomical site of the GABAergic inhibition of cerebral serotonergic neurons.

Acute injection of the gamma-aminobutyric acid (GABA) mimetics progabide, aminooxyacetic acid, gamma-acetylenic GABA and dipropylacetamide reduced 5-hydroxytryptophan (5-HTP) accumulation in serotonergic nerve terminal regions (prefrontal cortex, olfactory tubercle, septum, striatum, hypothalamus, hippocampus, substantia nigra, cerebellum and spinal cord) as well as in corresponding cell body areas (raphé dorsalis, medianus, pontis and magnus). This effect was antagonized by bicuculline. The inhibition of serotonin (5-HT) synthesis induced by a single progabide administration was accentuated on repeated treatment in the striatum, prefrontal cortex and cerebellum but was similar to that seen after acute treatment in the other areas. Local infusion of high concentrations of GABA or GABA mimetics into the striatum, septum or substantia nigra failed to modify 5-HTP accumulation in these areas. Cerebral hemitransection antagonized the ability of progabide (1200 mg/kg i.p.) to diminish 5-HTP accumulation in the striatum, hippocampus and prefrontal cortex. Intra-raphé dorsalis infusion of muscimol (0.1-100 ng) or GABA (1-100 micrograms) decreased 5-HT synthesis in the corresponding projection areas (e.g. striatum, substantia nigra, cortex) but not in the hippocampus or cerebellum. Conversely, intra-raphé medianus infusion of these drugs diminished 5-HTP accumulation in the corresponding projection areas (e.g. hippocampus, septum, cortex) but not in the striatum or cerebellum. Intra-raphé dorsalis or medianus injection of GABA antagonists (bicuculline, picrotoxinin, RU-5135) was without effect on cerebral 5-HT synthesis but antagonized the diminution of the amine synthesis observed in corresponding projection areas after intra-raphé dorsalis or medianus infusion of muscimol or GABA. These results suggest that GABA exerts an inhibitory (non-tonic) control over central serotonergic neurons which is mediated via GABA receptors located in the raphé nuclei.

5-Hydroxytryptophan↗
PubMed1995

Effects of JO 1784, a selective sigma ligand, on the autoradiographic localization of M1 and M2 muscarinic receptor subtypes in trimethyltin treated rats.

The distribution patterns of M1 and M2 muscarinic receptor subtypes following TMT and JO 1784 administration in the male Sprague-Dawley rat were investigated. In the present study, JO 1784 was injected in doses of 1, 4 and 16 mg/kg i.p. for one week prior to the single injection of TMT (8 mg/kg i.p.) and subsequently for 33 days. The effects of JO 1784 on the density of muscarinic receptor sub-types (M1 and M2) in the control and trimethyltin (TMT) treated rats were then evaluated. The topographic distribution and changes in muscarinic (M1 and M2) receptor densities were determined by means of autoradiography using [3H]quinuclidinylbenzilate (QNB). Both sub-types of muscarinic receptors contributed to the observed decrease in total muscarinic receptor binding in TMT-treated rats. In control rats, JO 1784 alone decreased M1 receptor density in the amygdaloid nuclei, basal ganglia, cortex and hippocampus and decreased M2 receptor density in the amygdaloid nuclei, basal ganglia, cortex, hippocampus, hypothalamus and septal regions. In TMT treated rats, chronic JO 1784 administration has a "neuroprotective effect" on both M1 and M2 receptors subtypes. Thus, following chronic administration of JO 1784 to TMT treated rats, both increases and decreases in M1 receptor density were observed relative to TMT animals. A significant increase in M1 receptor density was found in the cortex, olfactory regions, septum, thalamus and basal forebrain nuclei. In the hippocampus (CA2 and CA3), a significant decrease in M1 receptor density was observed. In TMT-treated rats, JO 1784 produced a significant increase in M2, receptor density in several brain regions with the most marked effects occurring in the amygdaloid nuclei, basal ganglia, cortex, hippocampus and hypothalamus. The ability of the selective sigma ligand, JO 1784, to attenuate the loss of muscarinic receptors in TMT treated rats could be of importance in the development of novel neuroprotective drugs.

Animals↗
PubMed1987

Organization of cortical afferents to the frontal association cortex in dogs.

The source of cortical frontal association cortex (FAC) afferents and their terminal distribution in the dog's brain was determined by the HRP tracing method. It was shown that the sources of ipsilateral FAC afferents are limbic and paralimbic areas of allo- and mesocortex and parasensory areas of the neocortex. Most of these areas with the exception of the piriform olfactory cortex could be characterized as cortical association fields. The terminal distribution of FAC afferents gave evidence to distinguish dorsal and ventral FAC zones. The dorsal FAC zone which includes the premotor and dorsal prefrontal regions is supplied by afferents originating in the temporal, parietal, occipital, perirhinal and parahippocampal cortical areas. In contrast, the ventral FAC zone, involving the ventral part of the prefrontal cortex, receives characteristic projections from the subcallosal area and from the anterior parts of the piriform cortex. However, both FAC zones receive intensive projections from the cingular and insular cortices. The organization of FAC afferents in the dog was discussed in comparison with other species.

Afferent Pathways↗
PubMed1988

Chronic intracerebroventricular infusion of insulin failed to alter brain insulin-binding sites, food intake, and body weight.

The present study was performed to explore the role of exogenous insulin in CSF in the control of energy balance in the rat. For this purpose, adult male Sprague-Dawley rats carrying an indwelling cannula in the right lateral cerebral ventricle were infused for a maximum of 10 days with insulin (Actrapid) at various rates (starting at 0, 45, 85, 170, and 600 ng/day) or anti-insulin antibody (IgG fraction; diluted 1:10 wt/vol) with an osmotic minipump. All those treatments did not modify the growing rates; neither total daily food intake nor the circadian rhythm of food intake was further modified. The chronic insulin infusion starting at 600 ng/day resulted in a chronic significant increase in CSF insulin levels without changing the plasma insulin level. It failed to alter specific insulin binding sites to Triton X-100 solubilized microsomal membranes from various brain areas (cerebral cortex, olfactory bulbs, and lateral and medial hypothalami) at the end of the 5- or 10-day period of insulin infusion. Purification of insulin receptors on a wheat germ agglutinin did not reveal any further effect of insulin. From these results, it seems unlikely that the input to the brain insulin-effector systems could arise from CSF insulin.

Animals↗