öVisceral sensory perception is subjected to modulation by attention or distraction, like other s... more öVisceral sensory perception is subjected to modulation by attention or distraction, like other sensory systems. The thalamic reticular nucleus is a key region in selective attention, e¡ecting a change in the mode of thalamocortical transmission. Each major thalamocortical system is connected with a particular sector of the thalamic reticular nucleus. No connections from the thalamic reticular nucleus have been described to the visceral sensory thalamus. We used axonal tracing techniques to study the possible existence of reciprocal connections between the visceral sensory relay in the lateral ventroposterior parvicellular thalamic nucleus, and the reticular nucleus of the thalamus. We also studied the projections from the visceral sensory cortex, located in the granular insular cortex in the rat, to the reticular nucleus of the thalamus. We found a convergent input from both thalamic and cortical sensory visceral regions to the same sector of the reticular nucleus of the thalamus. This visceral sector in turn sent GABAergic feedback connections to the lateral ventroposterior parvicellular thalamic nucleus. In addition, the visceral thalamus received histaminergic projections from the tuberomammillary nucleus, and noradrenergic projections from the locus coeruleus; both nuclei belong to the ascending activating system. Our ¢ndings indicate that the visceral sensory thalamocortical pathway is connected to the same subcortical structures that provide attention mechanisms for other thalamocortical systems.
IL disinhibition or enticement induce an histamine dependent temperature increase. • IL inhibitio... more IL disinhibition or enticement induce an histamine dependent temperature increase. • IL inhibition reduces termal and motor responses to food enticement. • Propanolol reduces temperature but not motor activity increase induced by IL disinhibition.
The sensory discharges from the carotid body chemoreceptors of the cat are transiently inhibited ... more The sensory discharges from the carotid body chemoreceptors of the cat are transiently inhibited by dopamine (DA) injections. This chemosensory inhibition was effectively blocked by domperidone, a selective antagonist of D2 dopaminoceptors. The basal frequency of spontaneous chemosensory impulses was immediately and sustainly increased after domperidone, suggesting the withdrawal of a tonic inhibition of chemosensory discharges by endogenous DA released from glomus cells. The peripheral dopaminergic modulation of chemoreflexes may be separately blocked by domperidone, a drug unable to cross the blood-brain barrier.
Ahatraet-The presence and distribution of the calcitonin gene-related peptide was studied, using ... more Ahatraet-The presence and distribution of the calcitonin gene-related peptide was studied, using immunohistocbemical techniques, in carotid receptors, in the nodose and glossopharyngeal ganglia and in the nucleus tractus solitarii of the cat. Seventy-seven per cent of the petrosal and 42% of the nodose ganglion cells were labeled. Fine, sparsely branched immunoreactive terminal axonal arborizations were found in the carotid body; they disappeared after petrosal ganglionectomy. The intense immunoreactivity present in fibers in the commissural, medial, interstitial, gelatinosus, dorsal, intermediate and rostra1 gustatory subnuclei of the nucleus tractus solitarius was drastically reduced after removal of the ipsilateral nodose and petrosal ganglia. The central distribution of the immunoreactive axons, the morphology of the terminals in the carotid receptors and theii dependence on an intact peripheral innervation are consistent with the idea that in the cat the cakitonin gene-related peptide is present in a high proportion of the primary visceral afferents, most of them unmyelinated.
Efferent and afferent connections of the visually responsive cortex (area anteromedial, AM) locat... more Efferent and afferent connections of the visually responsive cortex (area anteromedial, AM) located in the anterior portion of area 18b were studied with degeneration and horseradish peroxidase (HRP) methods following small lesions and HRP injections into this area. Degenerating axons, terminals and retrogradely HRP-labeled neurons were observed in a broad region of the cortex including areas located lateral, medial and anterior to the striate cortex. The main finding of this study is that connections of area AM with area 18a are distributed in discrete patches whose arrangement is similar to that of the lateral extrastriate visual areas postulated in previous physiological and anatomical reports. These results thus suggest that visual area AM is reciprocally connected with visual areas in area 18a. Area AM is also connected with other regions within area 18b, thus supporting the notion advanced by recent studies that area 18b contains more than one visual area. A weak afferent connection to area AM from the dorsal lateral geniculate nucleus of the thalamus was noted. Previously described connections of area 18b with areas 8 and 29 as well as with the lateral and latero-posterior thalamic nuclei were confirmed in the present study.
The projections of coarse and fine axons of the glossopharyngeal (IX) nerve upon the caudal two t... more The projections of coarse and fine axons of the glossopharyngeal (IX) nerve upon the caudal two thirds of the nucleus of the tractus solitarius (NTS) were studied in the cat. These afferents convey the chemo-and baroreceptor activities from the carotid receptors. We applied the Fink-Heimer method on brainstem sections, at different survival times, after a petrosal ganglionectomy. A segregation of fine and coarse fibered components was observed. Degeneration of coarse axons was mostly found in the lateral NTS, while fine fiber degeneration was predominant in regions of the medial and commissural NTS. The injection of WGA-HRP in the different NTS divisions demonstrated that the lateral NTS was mainly innervated by the set of largest neurons of the petrosal ganglion and that the medial and the commissural NTS were innervated by the set of smaller neurons of the ganglia. These results were discussed in relation to cytoarchitecture, myeloarchitecture, distribution of normal axons, and known central connectivity of the different NTS divisions. We concluded that coarse and fine visceral afferents of the IX nerve, which includes the afferents of the carotid body and the carotid sinus, represent different afferent populations that project to particular divisions of the NTS and connect to different central pathways.
We show here that the retina is represented in the cat's optic tract by several separate, retinot... more We show here that the retina is represented in the cat's optic tract by several separate, retinotopically organized maps. Fibers in different diameter classes form independent maps, and both hemiretinae of the opposite side, as well as the temporal retina of the same side, are mapped in the tract. These several maps form rough topographic representations significantly out of register with each other. The classical view of the mammalian optic tract is that there are two orderly maps of the contralateral visual hemifield, in register with each other in each tract 11,18, 24. One map comes from the temporal retina of the same side and the other comes from the nasal retina of the opposite side. However, there are some observations that do not
When food is available during a restricted and predictable time of the day, animals show increase... more When food is available during a restricted and predictable time of the day, animals show increased locomotor and food searching behaviors before the anticipated daily meal. We had shown that histamine-containing neurons are the only aminergic neurons related to arousal that become active in anticipation of an upcoming meal. To further map, the brain regions involved in the expression of the feeding-anticipatory behavior, we quantified the expression of Fos in hypothalamic areas involved in arousal. We found that nearly 35% of the histamine neurons from the tuberomammillary nucleus were Fos-immunoreactive immediately before mealtime. One hour before this transient increase in Fos-immunoreactivity, we found a similarly brief increase of fos mRNA in the tuberomammillary nucleus. In contrast, the activation of two types of perifornical hypothalamic neurons followed meal onset by 1-2 h. One neuron type was orexin/hypocretin-immunoreactive, while the other type was neither orexin nor melanin concentrating hormone-immunoreactive. The present work indicates that the increased locomotor activity that anticipates mealtime coincides with the activation of the tuberomammillary nucleus, and that the behavioral activation during the consummatory phase of feeding coincides more closely with the delayed activation of the perifornical hypothalamic area.
We tested the hypothesis that in primates, maternal melatonin restrains fetal and newborn adrenal... more We tested the hypothesis that in primates, maternal melatonin restrains fetal and newborn adrenal cortisol production. A functional G-protein-coupled MT1 membrane-bound melatonin receptor was detected in 90% gestation capuchin monkey fetal adrenals by (a) 2-[ 125 I] iodomelatonin binding (K d , 75.7 ± 6.9 pM; B max , 2.6 ± 0.4 fmol (mg protein) −1), (b) cDNA identification, and (c) melatonin inhibition of adrenocorticotrophic hormone (ACTH)-and corticotrophin-releasing hormone (CRH)-stimulated cortisol but not of dehydroepiandrosterone sulphate (DHAS) production in vitro. Melatonin also inhibited ACTHinduced 3β-hydroxysteroid dehydrogenase mRNA expression. To assess the physiological relevance of these findings, we next studied the effect of chronic maternal melatonin suppression (induced by exposure to constant light during the last third of gestation) on maternal plasma oestradiol during gestation and on plasma cortisol concentration in the 4-to 6-day-old newborn. Constant light suppressed maternal melatonin without affecting maternal plasma oestradiol concentration, consistent with no effect on fetal DHAS, the precursor of maternal oestradiol. However, newborns from mothers under constant light condition had twice as much plasma cortisol as newborns from mothers maintained under a normal light-dark schedule. Newborns from mothers exposed to chronic constant light and daily melatonin replacement had normal plasma cortisol concentration. Our results support a role of maternal melatonin in fetal and neonatal primate cortisol regulation.
The interesting observation was made 20 years ago that psychotic manifestations in patients with ... more The interesting observation was made 20 years ago that psychotic manifestations in patients with systemic lupus erythematosus are associated with the production of antiribosomal-P protein (anti-P) autoantibodies. Since then, the pathogenic role of anti-P antibodies has attracted considerable attention, giving rise to long-term controversies as evidence has either contradicted or confirmed their clinical association with lupus psychosis. Furthermore, a plausible mechanism supporting an anti-P–mediated neuronal dysfunction is still lacking. We show that anti-P antibodies recognize a new integral membrane protein of the neuronal cell surface. In the brain, this neuronal surface P antigen (NSPA) is preferentially distributed in areas involved in memory, cognition, and emotion. When added to brain cellular cultures, anti-P antibodies caused a rapid and sustained increase in calcium influx in neurons, resulting in apoptotic cell death. In contrast, astrocytes, which do not express NSPA, w...
Arousal depends on the concerted activity of the ascending arousal system (AAS) but specific stim... more Arousal depends on the concerted activity of the ascending arousal system (AAS) but specific stimuli may primarily activate some nuclei of this system. Motivated behaviours are characterized by behavioural arousal, although it is not known which AAS nuclei are active during a motivated behaviour. To address this issue, rats were rendered motivated for food by fasting them for 1 day and then were enticed with food that they could not obtain for varying periods of time. We studied the level of arousal by polysomnography or radiotelemetry, and Fos-ir in the AAS, during food enticing. We found a strong arousal and an early increase in Fos-ir in the histaminergic neurons from the tuberomammillary nucleus, after 30 min of enticing, followed by increased Fos-ir in the whole AAS if food enticing was prolonged to 1 or 2 hours. In contrast, food presentation to non-motivated rats did not increase arousal or Fos-ir in the tuberomammillary nucleus. As opposed to the active arousal of the motivated rats, passive arousal induced by sensory stimulation was associated with increased Fos-ir in the locus coeruleus and the orexin neurons, but not with increased Fos-ir in the tuberomammillary nucleus or in the other nuclei of the AAS. We conclude that the arousal during feeding-related motivated behaviour is associated primarily with the activation of the tuberomammillary nucleus, while the other arousal-related nuclei become active later on.
The circadian production of glucocorticoids involves the concerted action of several factors that... more The circadian production of glucocorticoids involves the concerted action of several factors that eventually allow an adequate adaptation to the environment. Circadian rhythms are controlled by the circadian timing system that comprises peripheral oscillators and a central rhythm generator located in the suprachiasmatic nucleus (SCN) of the hypothalamus, driven by the self-regulatory interaction of a set of proteins encoded by genes named clock genes. Here we describe the phase relationship between the SCN and adrenal gland for the expression of selected core clock transcripts (Per-2, Bmal-1) in the adult capuchin monkey, a New World, diurnal nonhuman primate. In the SCN we found a higher expression of Bmal-1 during the h of darkness (2000–0200 h) and Per-2 during daytime h (1400 h). The adrenal gland expressed clock genes in oscillatory fashion, with higher values for Bmal-1 during the day (1400–2000 h), whereas Per-2 was higher at nighttime (about 0200 h), resulting in a 9- to 12-...
We examined the possible existence of divergent visceral pathways arising from the nucleus of the... more We examined the possible existence of divergent visceral pathways arising from the nucleus of the solitary tract, by co-injecting axonal tracers into the parabrachial nucleus and into the ventrolateral medulla. We found that around 5% of NTS neurons projected to both sites, and that neurons projecting to VLM were larger. This parallel organization allows a differential control of the ascending versus descending visceral pathways at an early stage of processing.
The tuberomammillary nucleus (TMN) is the major source of histaminergic innervation of the mammal... more The tuberomammillary nucleus (TMN) is the major source of histaminergic innervation of the mammalian brain and is thought to play a major role in regulating wake-sleep states. We recently found that sleep-active neurons in the ventrolateral preoptic nucleus (VLPO) provide a major input to the TMN, but the specificity of this projection and the neurotransmitters involved remain unknown. In this study, we examined the relationship of VLPO efferents to the TMN using both retrograde and anterograde tracing, combined with immunocytochemistry. We found that the descending projection from the VLPO selectively targets the cell bodies and proximal dendrites of the histaminergic TMN. In addition, VLPO axons could be traced into the brainstem, where they provided terminals in the the serotoninergic dorsal and median raphe nuclei, and the core of the noradrenergic locus coeruleus. Approximately 80% of the VLPO neurons that were retrogradely labeled by tracer injections including the TMN were immunoreactive either for galanin or for glutamic acid decarboxylase (GAD), the synthetic enzyme for GABA. Virtually all of the galaninergic neurons in the VLPO were also GAD positive. Our results indicate that the VLPO may provide inhibitory GABAergic and galaninergic inputs to the cell bodies and proximal dendrites of the TMN and other components of the ascending monoaminergic arousal system. Because these cell groups are simultaneously inhibited during sleep, the VLPO sleep-active neurons may play a key role in silencing the ascending monoaminergic arousal system during sleep.
INTRODUCTION According to the model of emotions, feelings have their origin in the conscious perc... more INTRODUCTION According to the model of emotions, feelings have their origin in the conscious perception of body changes produced in response to an emotional stimulus. These changes are perceived thanks to the fact that they are represented in the brain by the interoceptive system. During abstinence, addicts experience intense feelings of ill-being that drive them to consume drugs. The purpose of this review is to discuss the role played by the interoceptive system, and more especially the insular cortex, in the perception of the negative feelings that characterise abstinence. DEVELOPMENT The continuous processing of interoceptive signals in the insular cortex is what accounts for the conscious appreciation of the body changes that accompany an emotional state. Temporary inactivation of the insular cortex suppresses the search for drugs in addicted rats. Neuroimaging studies reveal an increase in the neuronal activity in the insular cortex and in other areas of the brain while addict...
BACKGROUND Neosaxitoxin (NeoSTX) and related paralytics shellfish toxins has been successfully us... more BACKGROUND Neosaxitoxin (NeoSTX) and related paralytics shellfish toxins has been successfully used as local anesthetic and muscle relaxants to treat a variety of ailments. The primary mechanism of action of these toxins occurs by blocking voltage-gated sodium channels with compounds such as TTX, lidocaine, or derivatives. However, most of these non-classical sodium channel blockers act with a reduced time effect as well as ensuing neurotoxicity. NEW METHOD In this report, we show that the use of local NeoSTX injections inactivates the hippocampal neuronal activity reversibly with a by long-term dynamics, without neuronal damage. RESULTS A single 10 ng/μl injection of NeoSTX in the dorsal CA1 region abolished for up to 48 h memory capacities and neuronal activity measured by the neuronal marker c-fos. After 72 h of toxin injection, the animals fully recover their memory capacities and hippocampal neuronal activity. The histological inspection of NeoSTX injected brain regions revealed no damage to the tissue or reactive gliosis, similar to vehicle injection. Acute electrophysiological recording in vivo shows, also, minimal spreading of the NeoSTX in the cerebral tissue. COMPARISON WITH EXISTING METHODS Intracerebral NeoSTX injection showed longer effects than other voltage sodium channel blocker, with minimal spreading and no neuronal damage. CONCLUSION NeoSTX is a new useful tool that reversibly inactivates different brains region for a long time, with minimal diffusion and without neuronal damage. Moreover, NeoSTX can be used as a valuable sodium channel blocker for many studies in vivo and with potential therapeutic uses.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 1982
The topographic distribution of axons according to diameter classes in the optic tract of the cat... more The topographic distribution of axons according to diameter classes in the optic tract of the cat has been studied by light and electron microscopic methods. The subdivision of the tract into a ventral and a dorsal sector, with the former containing the thickest fibers of the tract, has been confirmed. In addition, there is a ventrolateral marginal zone of the tract which contains many of the finest axons and there are gradients of fiber diameters definable for thick and intermediate axons. The gradients show the thinner fibers lying rostral to the thicker fibers. The major points demonstrable by fiber diameter measurements have been confirmed by counts of myelin lamellae. Comparison of fiber distributions in the optic tract with the distributions in the optic nerve on the one hand and with the geniculate terminations on the other shows that, in the region of the optic chiasm, retinofugal axons are sorted not only according to their crossed or uncrossed pathway but also according to...
öVisceral sensory perception is subjected to modulation by attention or distraction, like other s... more öVisceral sensory perception is subjected to modulation by attention or distraction, like other sensory systems. The thalamic reticular nucleus is a key region in selective attention, e¡ecting a change in the mode of thalamocortical transmission. Each major thalamocortical system is connected with a particular sector of the thalamic reticular nucleus. No connections from the thalamic reticular nucleus have been described to the visceral sensory thalamus. We used axonal tracing techniques to study the possible existence of reciprocal connections between the visceral sensory relay in the lateral ventroposterior parvicellular thalamic nucleus, and the reticular nucleus of the thalamus. We also studied the projections from the visceral sensory cortex, located in the granular insular cortex in the rat, to the reticular nucleus of the thalamus. We found a convergent input from both thalamic and cortical sensory visceral regions to the same sector of the reticular nucleus of the thalamus. This visceral sector in turn sent GABAergic feedback connections to the lateral ventroposterior parvicellular thalamic nucleus. In addition, the visceral thalamus received histaminergic projections from the tuberomammillary nucleus, and noradrenergic projections from the locus coeruleus; both nuclei belong to the ascending activating system. Our ¢ndings indicate that the visceral sensory thalamocortical pathway is connected to the same subcortical structures that provide attention mechanisms for other thalamocortical systems.
IL disinhibition or enticement induce an histamine dependent temperature increase. • IL inhibitio... more IL disinhibition or enticement induce an histamine dependent temperature increase. • IL inhibition reduces termal and motor responses to food enticement. • Propanolol reduces temperature but not motor activity increase induced by IL disinhibition.
The sensory discharges from the carotid body chemoreceptors of the cat are transiently inhibited ... more The sensory discharges from the carotid body chemoreceptors of the cat are transiently inhibited by dopamine (DA) injections. This chemosensory inhibition was effectively blocked by domperidone, a selective antagonist of D2 dopaminoceptors. The basal frequency of spontaneous chemosensory impulses was immediately and sustainly increased after domperidone, suggesting the withdrawal of a tonic inhibition of chemosensory discharges by endogenous DA released from glomus cells. The peripheral dopaminergic modulation of chemoreflexes may be separately blocked by domperidone, a drug unable to cross the blood-brain barrier.
Ahatraet-The presence and distribution of the calcitonin gene-related peptide was studied, using ... more Ahatraet-The presence and distribution of the calcitonin gene-related peptide was studied, using immunohistocbemical techniques, in carotid receptors, in the nodose and glossopharyngeal ganglia and in the nucleus tractus solitarii of the cat. Seventy-seven per cent of the petrosal and 42% of the nodose ganglion cells were labeled. Fine, sparsely branched immunoreactive terminal axonal arborizations were found in the carotid body; they disappeared after petrosal ganglionectomy. The intense immunoreactivity present in fibers in the commissural, medial, interstitial, gelatinosus, dorsal, intermediate and rostra1 gustatory subnuclei of the nucleus tractus solitarius was drastically reduced after removal of the ipsilateral nodose and petrosal ganglia. The central distribution of the immunoreactive axons, the morphology of the terminals in the carotid receptors and theii dependence on an intact peripheral innervation are consistent with the idea that in the cat the cakitonin gene-related peptide is present in a high proportion of the primary visceral afferents, most of them unmyelinated.
Efferent and afferent connections of the visually responsive cortex (area anteromedial, AM) locat... more Efferent and afferent connections of the visually responsive cortex (area anteromedial, AM) located in the anterior portion of area 18b were studied with degeneration and horseradish peroxidase (HRP) methods following small lesions and HRP injections into this area. Degenerating axons, terminals and retrogradely HRP-labeled neurons were observed in a broad region of the cortex including areas located lateral, medial and anterior to the striate cortex. The main finding of this study is that connections of area AM with area 18a are distributed in discrete patches whose arrangement is similar to that of the lateral extrastriate visual areas postulated in previous physiological and anatomical reports. These results thus suggest that visual area AM is reciprocally connected with visual areas in area 18a. Area AM is also connected with other regions within area 18b, thus supporting the notion advanced by recent studies that area 18b contains more than one visual area. A weak afferent connection to area AM from the dorsal lateral geniculate nucleus of the thalamus was noted. Previously described connections of area 18b with areas 8 and 29 as well as with the lateral and latero-posterior thalamic nuclei were confirmed in the present study.
The projections of coarse and fine axons of the glossopharyngeal (IX) nerve upon the caudal two t... more The projections of coarse and fine axons of the glossopharyngeal (IX) nerve upon the caudal two thirds of the nucleus of the tractus solitarius (NTS) were studied in the cat. These afferents convey the chemo-and baroreceptor activities from the carotid receptors. We applied the Fink-Heimer method on brainstem sections, at different survival times, after a petrosal ganglionectomy. A segregation of fine and coarse fibered components was observed. Degeneration of coarse axons was mostly found in the lateral NTS, while fine fiber degeneration was predominant in regions of the medial and commissural NTS. The injection of WGA-HRP in the different NTS divisions demonstrated that the lateral NTS was mainly innervated by the set of largest neurons of the petrosal ganglion and that the medial and the commissural NTS were innervated by the set of smaller neurons of the ganglia. These results were discussed in relation to cytoarchitecture, myeloarchitecture, distribution of normal axons, and known central connectivity of the different NTS divisions. We concluded that coarse and fine visceral afferents of the IX nerve, which includes the afferents of the carotid body and the carotid sinus, represent different afferent populations that project to particular divisions of the NTS and connect to different central pathways.
We show here that the retina is represented in the cat's optic tract by several separate, retinot... more We show here that the retina is represented in the cat's optic tract by several separate, retinotopically organized maps. Fibers in different diameter classes form independent maps, and both hemiretinae of the opposite side, as well as the temporal retina of the same side, are mapped in the tract. These several maps form rough topographic representations significantly out of register with each other. The classical view of the mammalian optic tract is that there are two orderly maps of the contralateral visual hemifield, in register with each other in each tract 11,18, 24. One map comes from the temporal retina of the same side and the other comes from the nasal retina of the opposite side. However, there are some observations that do not
When food is available during a restricted and predictable time of the day, animals show increase... more When food is available during a restricted and predictable time of the day, animals show increased locomotor and food searching behaviors before the anticipated daily meal. We had shown that histamine-containing neurons are the only aminergic neurons related to arousal that become active in anticipation of an upcoming meal. To further map, the brain regions involved in the expression of the feeding-anticipatory behavior, we quantified the expression of Fos in hypothalamic areas involved in arousal. We found that nearly 35% of the histamine neurons from the tuberomammillary nucleus were Fos-immunoreactive immediately before mealtime. One hour before this transient increase in Fos-immunoreactivity, we found a similarly brief increase of fos mRNA in the tuberomammillary nucleus. In contrast, the activation of two types of perifornical hypothalamic neurons followed meal onset by 1-2 h. One neuron type was orexin/hypocretin-immunoreactive, while the other type was neither orexin nor melanin concentrating hormone-immunoreactive. The present work indicates that the increased locomotor activity that anticipates mealtime coincides with the activation of the tuberomammillary nucleus, and that the behavioral activation during the consummatory phase of feeding coincides more closely with the delayed activation of the perifornical hypothalamic area.
We tested the hypothesis that in primates, maternal melatonin restrains fetal and newborn adrenal... more We tested the hypothesis that in primates, maternal melatonin restrains fetal and newborn adrenal cortisol production. A functional G-protein-coupled MT1 membrane-bound melatonin receptor was detected in 90% gestation capuchin monkey fetal adrenals by (a) 2-[ 125 I] iodomelatonin binding (K d , 75.7 ± 6.9 pM; B max , 2.6 ± 0.4 fmol (mg protein) −1), (b) cDNA identification, and (c) melatonin inhibition of adrenocorticotrophic hormone (ACTH)-and corticotrophin-releasing hormone (CRH)-stimulated cortisol but not of dehydroepiandrosterone sulphate (DHAS) production in vitro. Melatonin also inhibited ACTHinduced 3β-hydroxysteroid dehydrogenase mRNA expression. To assess the physiological relevance of these findings, we next studied the effect of chronic maternal melatonin suppression (induced by exposure to constant light during the last third of gestation) on maternal plasma oestradiol during gestation and on plasma cortisol concentration in the 4-to 6-day-old newborn. Constant light suppressed maternal melatonin without affecting maternal plasma oestradiol concentration, consistent with no effect on fetal DHAS, the precursor of maternal oestradiol. However, newborns from mothers under constant light condition had twice as much plasma cortisol as newborns from mothers maintained under a normal light-dark schedule. Newborns from mothers exposed to chronic constant light and daily melatonin replacement had normal plasma cortisol concentration. Our results support a role of maternal melatonin in fetal and neonatal primate cortisol regulation.
The interesting observation was made 20 years ago that psychotic manifestations in patients with ... more The interesting observation was made 20 years ago that psychotic manifestations in patients with systemic lupus erythematosus are associated with the production of antiribosomal-P protein (anti-P) autoantibodies. Since then, the pathogenic role of anti-P antibodies has attracted considerable attention, giving rise to long-term controversies as evidence has either contradicted or confirmed their clinical association with lupus psychosis. Furthermore, a plausible mechanism supporting an anti-P–mediated neuronal dysfunction is still lacking. We show that anti-P antibodies recognize a new integral membrane protein of the neuronal cell surface. In the brain, this neuronal surface P antigen (NSPA) is preferentially distributed in areas involved in memory, cognition, and emotion. When added to brain cellular cultures, anti-P antibodies caused a rapid and sustained increase in calcium influx in neurons, resulting in apoptotic cell death. In contrast, astrocytes, which do not express NSPA, w...
Arousal depends on the concerted activity of the ascending arousal system (AAS) but specific stim... more Arousal depends on the concerted activity of the ascending arousal system (AAS) but specific stimuli may primarily activate some nuclei of this system. Motivated behaviours are characterized by behavioural arousal, although it is not known which AAS nuclei are active during a motivated behaviour. To address this issue, rats were rendered motivated for food by fasting them for 1 day and then were enticed with food that they could not obtain for varying periods of time. We studied the level of arousal by polysomnography or radiotelemetry, and Fos-ir in the AAS, during food enticing. We found a strong arousal and an early increase in Fos-ir in the histaminergic neurons from the tuberomammillary nucleus, after 30 min of enticing, followed by increased Fos-ir in the whole AAS if food enticing was prolonged to 1 or 2 hours. In contrast, food presentation to non-motivated rats did not increase arousal or Fos-ir in the tuberomammillary nucleus. As opposed to the active arousal of the motivated rats, passive arousal induced by sensory stimulation was associated with increased Fos-ir in the locus coeruleus and the orexin neurons, but not with increased Fos-ir in the tuberomammillary nucleus or in the other nuclei of the AAS. We conclude that the arousal during feeding-related motivated behaviour is associated primarily with the activation of the tuberomammillary nucleus, while the other arousal-related nuclei become active later on.
The circadian production of glucocorticoids involves the concerted action of several factors that... more The circadian production of glucocorticoids involves the concerted action of several factors that eventually allow an adequate adaptation to the environment. Circadian rhythms are controlled by the circadian timing system that comprises peripheral oscillators and a central rhythm generator located in the suprachiasmatic nucleus (SCN) of the hypothalamus, driven by the self-regulatory interaction of a set of proteins encoded by genes named clock genes. Here we describe the phase relationship between the SCN and adrenal gland for the expression of selected core clock transcripts (Per-2, Bmal-1) in the adult capuchin monkey, a New World, diurnal nonhuman primate. In the SCN we found a higher expression of Bmal-1 during the h of darkness (2000–0200 h) and Per-2 during daytime h (1400 h). The adrenal gland expressed clock genes in oscillatory fashion, with higher values for Bmal-1 during the day (1400–2000 h), whereas Per-2 was higher at nighttime (about 0200 h), resulting in a 9- to 12-...
We examined the possible existence of divergent visceral pathways arising from the nucleus of the... more We examined the possible existence of divergent visceral pathways arising from the nucleus of the solitary tract, by co-injecting axonal tracers into the parabrachial nucleus and into the ventrolateral medulla. We found that around 5% of NTS neurons projected to both sites, and that neurons projecting to VLM were larger. This parallel organization allows a differential control of the ascending versus descending visceral pathways at an early stage of processing.
The tuberomammillary nucleus (TMN) is the major source of histaminergic innervation of the mammal... more The tuberomammillary nucleus (TMN) is the major source of histaminergic innervation of the mammalian brain and is thought to play a major role in regulating wake-sleep states. We recently found that sleep-active neurons in the ventrolateral preoptic nucleus (VLPO) provide a major input to the TMN, but the specificity of this projection and the neurotransmitters involved remain unknown. In this study, we examined the relationship of VLPO efferents to the TMN using both retrograde and anterograde tracing, combined with immunocytochemistry. We found that the descending projection from the VLPO selectively targets the cell bodies and proximal dendrites of the histaminergic TMN. In addition, VLPO axons could be traced into the brainstem, where they provided terminals in the the serotoninergic dorsal and median raphe nuclei, and the core of the noradrenergic locus coeruleus. Approximately 80% of the VLPO neurons that were retrogradely labeled by tracer injections including the TMN were immunoreactive either for galanin or for glutamic acid decarboxylase (GAD), the synthetic enzyme for GABA. Virtually all of the galaninergic neurons in the VLPO were also GAD positive. Our results indicate that the VLPO may provide inhibitory GABAergic and galaninergic inputs to the cell bodies and proximal dendrites of the TMN and other components of the ascending monoaminergic arousal system. Because these cell groups are simultaneously inhibited during sleep, the VLPO sleep-active neurons may play a key role in silencing the ascending monoaminergic arousal system during sleep.
INTRODUCTION According to the model of emotions, feelings have their origin in the conscious perc... more INTRODUCTION According to the model of emotions, feelings have their origin in the conscious perception of body changes produced in response to an emotional stimulus. These changes are perceived thanks to the fact that they are represented in the brain by the interoceptive system. During abstinence, addicts experience intense feelings of ill-being that drive them to consume drugs. The purpose of this review is to discuss the role played by the interoceptive system, and more especially the insular cortex, in the perception of the negative feelings that characterise abstinence. DEVELOPMENT The continuous processing of interoceptive signals in the insular cortex is what accounts for the conscious appreciation of the body changes that accompany an emotional state. Temporary inactivation of the insular cortex suppresses the search for drugs in addicted rats. Neuroimaging studies reveal an increase in the neuronal activity in the insular cortex and in other areas of the brain while addict...
BACKGROUND Neosaxitoxin (NeoSTX) and related paralytics shellfish toxins has been successfully us... more BACKGROUND Neosaxitoxin (NeoSTX) and related paralytics shellfish toxins has been successfully used as local anesthetic and muscle relaxants to treat a variety of ailments. The primary mechanism of action of these toxins occurs by blocking voltage-gated sodium channels with compounds such as TTX, lidocaine, or derivatives. However, most of these non-classical sodium channel blockers act with a reduced time effect as well as ensuing neurotoxicity. NEW METHOD In this report, we show that the use of local NeoSTX injections inactivates the hippocampal neuronal activity reversibly with a by long-term dynamics, without neuronal damage. RESULTS A single 10 ng/μl injection of NeoSTX in the dorsal CA1 region abolished for up to 48 h memory capacities and neuronal activity measured by the neuronal marker c-fos. After 72 h of toxin injection, the animals fully recover their memory capacities and hippocampal neuronal activity. The histological inspection of NeoSTX injected brain regions revealed no damage to the tissue or reactive gliosis, similar to vehicle injection. Acute electrophysiological recording in vivo shows, also, minimal spreading of the NeoSTX in the cerebral tissue. COMPARISON WITH EXISTING METHODS Intracerebral NeoSTX injection showed longer effects than other voltage sodium channel blocker, with minimal spreading and no neuronal damage. CONCLUSION NeoSTX is a new useful tool that reversibly inactivates different brains region for a long time, with minimal diffusion and without neuronal damage. Moreover, NeoSTX can be used as a valuable sodium channel blocker for many studies in vivo and with potential therapeutic uses.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 1982
The topographic distribution of axons according to diameter classes in the optic tract of the cat... more The topographic distribution of axons according to diameter classes in the optic tract of the cat has been studied by light and electron microscopic methods. The subdivision of the tract into a ventral and a dorsal sector, with the former containing the thickest fibers of the tract, has been confirmed. In addition, there is a ventrolateral marginal zone of the tract which contains many of the finest axons and there are gradients of fiber diameters definable for thick and intermediate axons. The gradients show the thinner fibers lying rostral to the thicker fibers. The major points demonstrable by fiber diameter measurements have been confirmed by counts of myelin lamellae. Comparison of fiber distributions in the optic tract with the distributions in the optic nerve on the one hand and with the geniculate terminations on the other shows that, in the region of the optic chiasm, retinofugal axons are sorted not only according to their crossed or uncrossed pathway but also according to...
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Papers by F. Torrealba