Anne Bérod - Academia.edu (original) (raw)
Papers by Anne Bérod
European Journal of Neuroscience, 2007
The ventral tegmental area (VTA), primary source of the mesocorticolimbic dopaminergic system, is... more The ventral tegmental area (VTA), primary source of the mesocorticolimbic dopaminergic system, is regarded as a critical site for initiation of behavioural sensitization to psychostimulants. The present study was undertaken to identify the neural pathways converging on the VTA that are potentially implicated in this process. Rats were sensitized by a single exposure to amphetamine (5 mg ⁄ kg, s.c.). The distribution of VTA-projecting neurons activated by amphetamine was examined by combining retrograde transport of the cholera toxin b subunit (CTb), injected into the VTA, with immunodetection of Fos. The quantitative analysis of CTb-Fos double labelling demonstrates that amphetamine induced a rapid activation of Fos in a large number of brain areas projecting to the VTA. More than half of the CTb-Fos double-labelled neurons were located in the prefrontal cortex, lateral preoptic area-lateral hypothalamus, pontomesencephalic tegmentum, dorsal raphe nucleus, ventral pallidum and nucleus accumbens. In addition, scattered CTb-Fos double-labelled cells were observed in many other VTA afferent structures, such as claustrum, lateral septum, diagonal band-magnocellular preoptic nucleus, deep mesencephalic nucleus, oral part of pontine reticular nucleus and dorsomedial tegmental area. This suggests that systemic amphetamine activates a wide population of neurons projecting to the VTA that may be important for the modulation of neurobehavioural plasticity produced by this psychostimulant.
Neuroscience, 1990
Previous deafferentation studies have suggested that most hypothalamic GABAergic innervation orig... more Previous deafferentation studies have suggested that most hypothalamic GABAergic innervation originates from neurons within the hypothalamus. We have investigated the distribution of GABAergic cell groups in the rat hypothalamus by means of the in situ hybridization technique, using a cDNA probe for messenger RNA encoding glutamate decarboxylase. Several major GABAergic cell groups were demonstrated, including cells of the tuberomammillary nucleus, arcuate nucleus, suprachiasmatic nucleus, medial preoptic area, anterior hypothalamic area, the dorsomedial hypothalamic nucleus, perifornical area, and lateral hypothalamic area. The most prominent glutamate decarboxylase mRNA-containing cell groups were located in the medial preoptic area, anterior hypothalamic area and dorsomedial hypothalamic nucleus, and were composed of small- to medium-sized neurons. Compared to previously well-characterized GABAergic cell groups in the tuberomammillary nucleus, reticular thalamic nucleus, and non-...
Ideggyógyászati szemle, Jan 30, 2007
Neurons expressing VIP/PHI precursor mRNA have been localized in the interstitial nucleus of Caja... more Neurons expressing VIP/PHI precursor mRNA have been localized in the interstitial nucleus of Cajal. Unilateral surgical cut through the medial forebrain bundle failed to influence VIP/PHI mRNA expression in the Cajal nucleus while brainstem hemisection or unilateral transection of the medial longitudinal fascicle reduced it markedly, ipsilateral to the knife cuts. Thus, in contrast to forebrain projecting VIP neurons in the rostral periaqueductal gray, VIP/PHI neurons in the Cajal nucleus project downwards, to the lower brainstem.
Comptes rendus de l'Académie des sciences. Série III, Sciences de la vie, 1984
The expression of tyrosine-hydroxylase (TH) gene was analysed in tissue sections of bovine adrena... more The expression of tyrosine-hydroxylase (TH) gene was analysed in tissue sections of bovine adrenal glands, by in situ hybridization using a single-stranded cDNA probe. Tissue fixation and hybridization conditions were found that led to a specific and sensitive detection of TH.
NeuroReport, 2007
This study examined the long-term e¡ects of the antidepressant escitalopram on rat serotonin (5-H... more This study examined the long-term e¡ects of the antidepressant escitalopram on rat serotonin (5-HT) neuronal activity and hippocampal neuroplasticity. In the dorsal raphe nucleus, a 2-week treatment with escitalopram (10 mg/kg/day, subcutaneous) did not modify the ¢ring activity of 5-HT neurons, whereas a cotreatment with R-citalopram (20 mg/kg/day, subcutaneous) decreased it. In the dentate gyrus of dorsal hippocampus, escitalopram increased signi¢cantly (57%) the number of de novo cells and this was prevented by a cotreatment with R-citalopram. The present results support the role of the allosteric modulation of the 5-HT transporter in the regulation of the recovery of 5-HT neuronal activity and long-lasting hippocampal cellular plasticity induced by escitalopram, two adaptive changes presumably associated with the antidepressant response.
Proceedings of the National Academy of Sciences, 1987
A rat tyrosine hydroxylase [TyrOHase; tyrosine 3-monooxygenase; L-tyrosine, tetrahydropteridine:o... more A rat tyrosine hydroxylase [TyrOHase; tyrosine 3-monooxygenase; L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating); EC 1.14.16.2] cDNA probe was used for in situ hybridization studies on histological sections through the locus coeruleus, substantia nigra, and the ventral tegmental area of the rat brain. Experimental conditions were established that yielded no background and no signal when pBR322 was used as a control probe. Using the tyrosine hydroxylase probe, we ascertained the specificity of the labeling over catecholaminergic cells by denervation experiments and comparison of the hybridization pattern with that of immunoreactivity. The use of 35S-labeled probe enabled the hybridization signal to be resolved at the cellular level. A single injection of reserpine into the rat led to an increase of the intensity of the autoradiographic signal over the locus coeruleus area, confirming an RNA gel blot analysis. The potential of in situ hybridization to analyze patterns of modulation of gene activity as a result of nervous activity is discussed.
PLoS ONE, 2009
Paradoxical sleep (PS) is a state characterized by cortical activation, rapid eye movements and m... more Paradoxical sleep (PS) is a state characterized by cortical activation, rapid eye movements and muscle atonia. Fifty years after its discovery, the neuronal network responsible for the genesis of PS has been only partially identified. We recently proposed that GABAergic neurons would have a pivotal role in that network. To localize these GABAergic neurons, we combined immunohistochemical detection of Fos with non-radioactive in situ hybridization of GAD67 mRNA (GABA synthesis enzyme) in control rats, rats deprived of PS for 72 h and rats allowed to recover after such deprivation. Here we show that GABAergic neurons gating PS (PS-off neurons) are principally located in the ventrolateral periaqueductal gray (vlPAG) and the dorsal part of the deep mesencephalic reticular nucleus immediately ventral to it (dDpMe). Furthermore, iontophoretic application of muscimol for 20 min in this area in head-restrained rats induced a strong and significant increase in PS quantities compared to saline. In addition, we found a large number of GABAergic PS-on neurons in the vlPAG/dDPMe region and the medullary reticular nuclei known to generate muscle atonia during PS. Finally, we showed that PS-on neurons triggering PS localized in the SLD are not GABAergic. Altogether, our results indicate that multiple populations of PS-on GABAergic neurons are distributed in the brainstem while only one population of PS-off GABAergic neurons localized in the vlPAG/dDpMe region exist. From these results, we propose a revised model for PS control in which GABAergic PS-on and PS-off neurons localized in the vlPAG/dDPMe region play leading roles.
PLoS ONE, 2010
We recently discovered, using Fos immunostaining, that the tuberal and mammillary hypothalamus co... more We recently discovered, using Fos immunostaining, that the tuberal and mammillary hypothalamus contain a massive population of neurons specifically activated during paradoxical sleep (PS) hypersomnia. We further showed that some of the activated neurons of the tuberal hypothalamus express the melanin concentrating hormone (MCH) neuropeptide and that icv injection of MCH induces a strong increase in PS quantity. However, the chemical nature of the majority of the neurons activated during PS had not been characterized. To determine whether these neurons are GABAergic, we combined in situ hybridization of GAD 67 mRNA with immunohistochemical detection of Fos in control, PS deprived and PS hypersomniac rats. We found that 74% of the very large population of Fos-labeled neurons located in the tuberal hypothalamus after PS hypersomnia were GAD-positive. We further demonstrated combining MCH immunohistochemistry and GAD 67 in situ hybridization that 85% of the MCH neurons were also GAD-positive. Finally, based on the number of Fos-ir/GAD + , Fos-ir/ MCH + , and GAD + /MCH + double-labeled neurons counted from three sets of double-staining, we uncovered that around 80% of the large number of the Fos-ir/GAD + neurons located in the tuberal hypothalamus after PS hypersomnia do not contain MCH. Based on these and previous results, we propose that the non-MCH Fos/GABAergic neuronal population could be involved in PS induction and maintenance while the Fos/MCH/GABAergic neurons could be involved in the homeostatic regulation of PS. Further investigations will be needed to corroborate this original hypothesis.
Peptides, 2006
Neurotensin (NT) is a peptide that is widely distributed throughout the brain. NT is involved in ... more Neurotensin (NT) is a peptide that is widely distributed throughout the brain. NT is involved in locomotion, reward, stress and pain modulation, and in the pathophysiology of drug addiction and depression. In its first part this review brings together relevant literature about the neuroanatomy of NT and its receptors. The second part focuses on functional-anatomical interactions between NT, the mesotelencephalic dopamine system and structures targeted by dopaminergic projections. Finally, recent data about the actions of NT in processes underlying behavioral sensitization to psychostimulant drugs and the involvement of NT in the regulation of the hypothalamo-pituitary-adrenal gland axis are considered.
Pediatric Research, 2002
Catecholamine release from the adrenal medulla glands plays a vital role in postnatal adaptation.... more Catecholamine release from the adrenal medulla glands plays a vital role in postnatal adaptation. A number of pathologic situations are characterized by oxygen deficiency. The objective of the present study was to determine the influence of long-term prenatal hypoxia on maturation of the adrenal medulla. Pregnant rats were subjected to hypoxia (10% O 2 ) from the fifth to the 20th d of gestation. The offspring were examined on the 19th d of gestation (E19), the day of birth (P0), and at postnatal (P) day of life P3, P7, P14, P21, and P68. The catecholamine content and activity of tyrosine hydroxylase (TH) in vivo were assayed by HPLC with electrochemical detection. Cellular expression of TH and phenylethanolamine N-methyl transferase was evaluated by protein immunohistochemistry and in situ hybridization of the corresponding mRNA species. Exposure to prenatal hypoxia reduced the epinephrine content of the adrenal medulla on E19, P0, P3, and P7 while increasing the norepinephrine content on E19, P0, and P14. Furthermore, the peak epinephrine to norepinephrine ratio appearing between P7 and P10 in the normoxic offspring was absent in the hypoxic offspring. The in vivo TH activity was increased on P3 and P14 and decreased on P68. The percentage of chromaffin cells in the medulla expressing TH and phenylethanolamine N-methyl transferase was lowered on E19, P0, and P7. TH and phenylethanolamine N-methyl transferase mRNA levels were reduced on P7. Clearly prenatal hypoxia results in major changes in adrenal catecholamine stores and synthesis during the perinatal period, which persist into adulthood. The capacity to cope with postnatal stress might be disturbed as a consequence of prenatal hypoxia. (Pediatr Res 51: 207-214, 2002) Abbreviations DOPA, L-3,4-dihydroxyphenylalanine E, epinephrine E19, d 19 of embryogenesis HPLC-ED, HPLC with electrochemical detection Hx, hypoxic NE, norepinephrine Nx, normoxic PNMT, phenylethanolamine N-methyl transferase P0, day of birth P3, d 3 of postnatal life P7, d 7 of postnatal life P14, d 14 of postnatal life P21, d 21 of postnatal life P68, d 68 of postnatal life TH, tyrosine hydroxylase 11 -OHSD, 11-hydroxysteroid dehydrogenase
Neuroscience Letters, 1989
The existence of GABAergic neurons in the rat suprachiasmatic nucleus (SCN) was demonstrated by t... more The existence of GABAergic neurons in the rat suprachiasmatic nucleus (SCN) was demonstrated by three specific markers; mRNA coding for glutamic acid decarboxylase (GAD) and visualized by in situ hybridization using a 35S-labelled cDNA probe, and GAD protein and GABA were identified by immunocytochemistry using specific antisera. In situ hybridization demonstrated well labelled GAD mRNA positive cells throughout SCN, and GABA and GAD immunoreactive cells showed similar distributions. These results indicate that GABA is a transmitter of a large portion of the SCN neuronal population.
Neuroscience Letters, 1994
In the present study, we examined the regulation of neurotensin receptor following a chronic phar... more In the present study, we examined the regulation of neurotensin receptor following a chronic pharmacological blockade of the neurotensin transmission with a nonpeptide neurotensin receptor antagonist, SR 48692. Our results showed that treatment of the rats for five days with SR 48692, at a dose of 1 mg/kg, i.p., induced an increase of both the number of binding sites for 125I-neurotensin to whole brain membrane homogenates and neurotensin receptor mRNA levels in the ventral mesencephalon. This study brings the first evidence for an in vivo up-regulation of neurotensin receptors following their pharmacological blockade, and suggests that endogenous neurotensin exerts a tonic inhibitory control on neurotensin receptor mRNA levels.
Neuroscience Letters, 1991
Neuromedin N (NN) is a hexapeptide that shares a four amino acid identity with the C-terminus of ... more Neuromedin N (NN) is a hexapeptide that shares a four amino acid identity with the C-terminus of neurotensin (NT) and exhibits NT-like effects in the central nervous system. Both peptides were recently shown to be encoded in the same precursor molecule. By means of specific and sensitive radioimmunoassays, we compared the distribution of immunoreactive NT and NN (iNT and iNN) in micropunched rat brain structures. The data revealed marked regional variations in the ratio of iNT over iNN. For instance, the ratio value was 4.5 in the posterior hypothalamus and 0.8 in the mammillary bodies. Reverse phase HPLC analysis of extracts of several brain regions showed that iNT and iNN coeluted with synthetic NT and NN, respectively. The results suggest that differential processing of the common neurotensin/neuromedin N precursor occurs in various regions of the rat brain.
Neuroscience, 2006
Osmoprotective genes are tonicity-activated genes involved in cellular osmoadaptation to hyperton... more Osmoprotective genes are tonicity-activated genes involved in cellular osmoadaptation to hypertonicity and considered to be regulated by a specific transcription factor called tonicity-responsive enhancer-binding protein (TonEBP). In the brain we had previously established that TonEBP was expressed and tonicity-induced in neurons only. Here we have compared in various brain regions of rats subjected to systemic hypertonicity, the cellular expression of TonEBP through immunocytochemistry and the cellular expression of osmoprotective genes, namely aldose reductase (AR), sodium-dependent myo-inositol transporter (SMIT), betaine/GABA transporter (BGT1) and taurine transporter (TauT), by in situ hybridization using non-radioactive digoxigenin-labeled riboprobes. In neurons where TonEBP was strongly tonicity-induced, AR-mRNA labeling was strongly increased in some subsets (e.g. hippocampus pyramidal cells, cerebellar Purkinje cells and neurons of the hypothalamic magnocellular nuclei) but remained undetectable in some other subsets (e.g. neurons in cerebral cortex). Tonicity-induced AR-mRNA labeling was observed only several hours after the tonicity-induced expression of TonEBP. SMIT-mRNA labeling was tonicity-induced as densely and evenly distributed dots in neuron poor regions (e.g. cerebral cortex layer I and hippocampus stratum lacunosum-moleculare). The tonicity-induced expression of SMIT-mRNA may thus occur in non-neuronal cells, presumably astrocytes, where TonEBP is neither significantly expressed, nor tonicity-induced. In neurons showing a strong tonicity-induced expression of TonEBP, no SMIT-mRNA labeling was observed. BGT1-mRNA and TauT-mRNA labeling could not be detected, even after systemic hypertonicity. The present work reveals large discrepancies between the cellular distribution of the tonicity-induced expression of osmoprotective genes and that of their regulatory transactivator TonEBP. Depending on the cell subsets and the osmoprotective genes, TonEBP may appear insufficient or conversely unnecessary for the tonicity-induced activation of an osmoprotective gene. Altogether our results show that brain cells, even from the same class, activate distinct osmoprotective genes through distinct activation processes to adapt to hypertonicity.
Neuroscience, 2008
5-HT 1A autoreceptors regulate the firing of 5-HT neurons and their release of 5-HT. In previous ... more 5-HT 1A autoreceptors regulate the firing of 5-HT neurons and their release of 5-HT. In previous immuno-electron microscopic studies, we have demonstrated an internalization of 5-HT 1A autoreceptors in the nucleus raphe dorsalis (NRD) of rats, after the acute administration of a single dose o f t h e specific agonist 8-hydroxy-2-(di-n-propylamine)tetralin (8-OH-DPAT) o r o f t h e selective 5-HT reuptake inhibitor, fluoxetine. Twenty-four hours after either treatment, the receptors were back in normal density on the plasma membrane of NRD neurons. Here, we examined the subcellular localization of these receptors and the in vivo binding of the 5-HT 1A radioligand 4,2-(methoxyphenyl)-1-[2-(N-2-pyridinyl)-p-fluorobenzamido]ethylpiperazine labeled with [ 18 F]fluorine ([ 18 F]MPPF)
Neuroscience, 1981
... scand. 64 (suppl. 247), 37-85.GALE K., HONG JS & GUIDOTTI A. (1977) Presence of substance... more ... scand. 64 (suppl. 247), 37-85.GALE K., HONG JS & GUIDOTTI A. (1977) Presence of substance P and GABA in separate striatonigral neurons. BrainRes. ... 11, 249-262.GROVES PM. WILSON CJ, YOUNG SJ & REBEC GV (1975) Self-inhibition by dopaminergic neurons. ...
Neuroscience, 2001
AbstractöThe morphological and physiological substrates that underlie the mutual regulatory inter... more AbstractöThe morphological and physiological substrates that underlie the mutual regulatory interactions of neurotensin and dopamine in the rat mesotelencephalic projections and related structures remain to be fully described. A salient candidate for neurotensinergic e¡ects on the mesotelencephalic dopamine projection is the dense plexus of neurotensin immunoreactive axons that enmeshes the ventral tegmental area and substantia nigra, but the locations of the neurons that give rise to this plexus have not been identi¢ed and its systemic context remains obscure. To address this, Fluoro-Gold and the cholera toxin L subunit, retrogradely transported axonal tracers, were injected into the ventral tegmental area of rats and the brains were processed to demonstrate neurons that contained both retrograde tracer immunoreactivity and a probe against neurotensin/neuromedin N messenger RNA. Substantial numbers of double-labeled neurons were observed in the rostral part of the lateral septum, and in a region centered on the shared boundaries of the bed nucleus of stria terminalis, ventromedial ventral pallidum, diagonal band of Broca, lateral preoptic area and rostral lateral hypothalamus. A few double-labeled neurons were also observed in the dorsal raphe nucleus and adjacent periaqueductal gray. Despite the administration of haloperidol and D-amphetamine to elicit and enhance neurotensin/ neuromedin N messenger RNA expression in striatum, including the nucleus accumbens and olfactory tubercle, no double-labeled neurons were observed there.
Neuroscience, 1983
The distribution of tyrosine hydroxylase-, substance P- and enkephalin-immunoreactive neurons in ... more The distribution of tyrosine hydroxylase-, substance P- and enkephalin-immunoreactive neurons in the cat dorsolateral pons was studied using the indirect immunofluorescence method of Coons. To allow for the visualization of substance P- and enkephalin-immunoreactive cell bodies, colchicine was injected either in the ventricular space or in the cerebral tissue. The distribution of the tyrosine hydroxylase-immunoreactive cell bodies corresponded with the well-known distribution of catecholamine cells in this area of the brain. The observation of adjacent sections treated separately with tyrosine hydroxylase- and enkephalin-antiserum revealed that most catecholaminergic cells contain enkephalin-immunoreactivity. In addition to this catecholamine-enkephalin cell population, a moderate number of substance P-immunoreactive cell bodies was found in dorsolateral pons. The peribrachial nuclei were found to be densely supplied with substance P- and enkephalin-immunoreactive fibers, whereas the medial subdivisions, which contain the majority of the catecholamine cells in the dorsolateral pons, display a moderate number of immunoreactive fibers. These results are suggestive of interactions between peptide-containing and catecholaminergic neurons and also between-peptide-containing and non-catecholamine-containing neurons in the cat dorsolateral pons.
Neuroscience, 1985
Double post-embedding immunolabehng of both tyrosine hydroxylase and glutamate decarboxylase on l... more Double post-embedding immunolabehng of both tyrosine hydroxylase and glutamate decarboxylase on l-pm semi-thin sections allowed the visualization of numerous endings that use y-aminobutyrate as a transmitter apposed to dopaminergic cell bodies in the periventricular-arcuate hypothalamic complex. Up to fifteen glutamate decarboxylase-positive contacts per tyrosine hydroxylasepositive cell profile could be observed. In some favourable planes of section glutamate dccarboxylasepositive endings were also seen in close apposition to proximal dopaminergic dendrites. About 250 tyrosine hydroxylase-positive cell profiles, whose diameter approached the maximum diameter of the dopaminergic cells, were surveyed. An average of 7.4 glutamate decarboxylase-positive contacts were counted on these profiles. From these figures it was estimated that a dopaminergic cell body was contacted on average by 75-175 terminals that use y-aminobutyrate as a transmitter. At the electron-microscopic level, the nature of these contacts was investigated by a method combining radioautographic detection of cell bodies having taken up tritiated dopamine and pre-embedding immunostaining of glutamate decarboxylase containing endings. Glutamate dccarboxylase-positive axon terminals were seen apposed to somatic and dendritic elements. On some favorable planes of section, they were found to be engaged in morphologically defined synaptic complexes of the symmetrical or asymmetrical type. A number of the postsynaptic perikarya were labelled by tritiated dopamine and, in agreement with the light microscopic observations, they were frequently seen in contact with more than one immunopositive ending.
European Journal of Neuroscience, 2007
The ventral tegmental area (VTA), primary source of the mesocorticolimbic dopaminergic system, is... more The ventral tegmental area (VTA), primary source of the mesocorticolimbic dopaminergic system, is regarded as a critical site for initiation of behavioural sensitization to psychostimulants. The present study was undertaken to identify the neural pathways converging on the VTA that are potentially implicated in this process. Rats were sensitized by a single exposure to amphetamine (5 mg ⁄ kg, s.c.). The distribution of VTA-projecting neurons activated by amphetamine was examined by combining retrograde transport of the cholera toxin b subunit (CTb), injected into the VTA, with immunodetection of Fos. The quantitative analysis of CTb-Fos double labelling demonstrates that amphetamine induced a rapid activation of Fos in a large number of brain areas projecting to the VTA. More than half of the CTb-Fos double-labelled neurons were located in the prefrontal cortex, lateral preoptic area-lateral hypothalamus, pontomesencephalic tegmentum, dorsal raphe nucleus, ventral pallidum and nucleus accumbens. In addition, scattered CTb-Fos double-labelled cells were observed in many other VTA afferent structures, such as claustrum, lateral septum, diagonal band-magnocellular preoptic nucleus, deep mesencephalic nucleus, oral part of pontine reticular nucleus and dorsomedial tegmental area. This suggests that systemic amphetamine activates a wide population of neurons projecting to the VTA that may be important for the modulation of neurobehavioural plasticity produced by this psychostimulant.
Neuroscience, 1990
Previous deafferentation studies have suggested that most hypothalamic GABAergic innervation orig... more Previous deafferentation studies have suggested that most hypothalamic GABAergic innervation originates from neurons within the hypothalamus. We have investigated the distribution of GABAergic cell groups in the rat hypothalamus by means of the in situ hybridization technique, using a cDNA probe for messenger RNA encoding glutamate decarboxylase. Several major GABAergic cell groups were demonstrated, including cells of the tuberomammillary nucleus, arcuate nucleus, suprachiasmatic nucleus, medial preoptic area, anterior hypothalamic area, the dorsomedial hypothalamic nucleus, perifornical area, and lateral hypothalamic area. The most prominent glutamate decarboxylase mRNA-containing cell groups were located in the medial preoptic area, anterior hypothalamic area and dorsomedial hypothalamic nucleus, and were composed of small- to medium-sized neurons. Compared to previously well-characterized GABAergic cell groups in the tuberomammillary nucleus, reticular thalamic nucleus, and non-...
Ideggyógyászati szemle, Jan 30, 2007
Neurons expressing VIP/PHI precursor mRNA have been localized in the interstitial nucleus of Caja... more Neurons expressing VIP/PHI precursor mRNA have been localized in the interstitial nucleus of Cajal. Unilateral surgical cut through the medial forebrain bundle failed to influence VIP/PHI mRNA expression in the Cajal nucleus while brainstem hemisection or unilateral transection of the medial longitudinal fascicle reduced it markedly, ipsilateral to the knife cuts. Thus, in contrast to forebrain projecting VIP neurons in the rostral periaqueductal gray, VIP/PHI neurons in the Cajal nucleus project downwards, to the lower brainstem.
Comptes rendus de l'Académie des sciences. Série III, Sciences de la vie, 1984
The expression of tyrosine-hydroxylase (TH) gene was analysed in tissue sections of bovine adrena... more The expression of tyrosine-hydroxylase (TH) gene was analysed in tissue sections of bovine adrenal glands, by in situ hybridization using a single-stranded cDNA probe. Tissue fixation and hybridization conditions were found that led to a specific and sensitive detection of TH.
NeuroReport, 2007
This study examined the long-term e¡ects of the antidepressant escitalopram on rat serotonin (5-H... more This study examined the long-term e¡ects of the antidepressant escitalopram on rat serotonin (5-HT) neuronal activity and hippocampal neuroplasticity. In the dorsal raphe nucleus, a 2-week treatment with escitalopram (10 mg/kg/day, subcutaneous) did not modify the ¢ring activity of 5-HT neurons, whereas a cotreatment with R-citalopram (20 mg/kg/day, subcutaneous) decreased it. In the dentate gyrus of dorsal hippocampus, escitalopram increased signi¢cantly (57%) the number of de novo cells and this was prevented by a cotreatment with R-citalopram. The present results support the role of the allosteric modulation of the 5-HT transporter in the regulation of the recovery of 5-HT neuronal activity and long-lasting hippocampal cellular plasticity induced by escitalopram, two adaptive changes presumably associated with the antidepressant response.
Proceedings of the National Academy of Sciences, 1987
A rat tyrosine hydroxylase [TyrOHase; tyrosine 3-monooxygenase; L-tyrosine, tetrahydropteridine:o... more A rat tyrosine hydroxylase [TyrOHase; tyrosine 3-monooxygenase; L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating); EC 1.14.16.2] cDNA probe was used for in situ hybridization studies on histological sections through the locus coeruleus, substantia nigra, and the ventral tegmental area of the rat brain. Experimental conditions were established that yielded no background and no signal when pBR322 was used as a control probe. Using the tyrosine hydroxylase probe, we ascertained the specificity of the labeling over catecholaminergic cells by denervation experiments and comparison of the hybridization pattern with that of immunoreactivity. The use of 35S-labeled probe enabled the hybridization signal to be resolved at the cellular level. A single injection of reserpine into the rat led to an increase of the intensity of the autoradiographic signal over the locus coeruleus area, confirming an RNA gel blot analysis. The potential of in situ hybridization to analyze patterns of modulation of gene activity as a result of nervous activity is discussed.
PLoS ONE, 2009
Paradoxical sleep (PS) is a state characterized by cortical activation, rapid eye movements and m... more Paradoxical sleep (PS) is a state characterized by cortical activation, rapid eye movements and muscle atonia. Fifty years after its discovery, the neuronal network responsible for the genesis of PS has been only partially identified. We recently proposed that GABAergic neurons would have a pivotal role in that network. To localize these GABAergic neurons, we combined immunohistochemical detection of Fos with non-radioactive in situ hybridization of GAD67 mRNA (GABA synthesis enzyme) in control rats, rats deprived of PS for 72 h and rats allowed to recover after such deprivation. Here we show that GABAergic neurons gating PS (PS-off neurons) are principally located in the ventrolateral periaqueductal gray (vlPAG) and the dorsal part of the deep mesencephalic reticular nucleus immediately ventral to it (dDpMe). Furthermore, iontophoretic application of muscimol for 20 min in this area in head-restrained rats induced a strong and significant increase in PS quantities compared to saline. In addition, we found a large number of GABAergic PS-on neurons in the vlPAG/dDPMe region and the medullary reticular nuclei known to generate muscle atonia during PS. Finally, we showed that PS-on neurons triggering PS localized in the SLD are not GABAergic. Altogether, our results indicate that multiple populations of PS-on GABAergic neurons are distributed in the brainstem while only one population of PS-off GABAergic neurons localized in the vlPAG/dDpMe region exist. From these results, we propose a revised model for PS control in which GABAergic PS-on and PS-off neurons localized in the vlPAG/dDPMe region play leading roles.
PLoS ONE, 2010
We recently discovered, using Fos immunostaining, that the tuberal and mammillary hypothalamus co... more We recently discovered, using Fos immunostaining, that the tuberal and mammillary hypothalamus contain a massive population of neurons specifically activated during paradoxical sleep (PS) hypersomnia. We further showed that some of the activated neurons of the tuberal hypothalamus express the melanin concentrating hormone (MCH) neuropeptide and that icv injection of MCH induces a strong increase in PS quantity. However, the chemical nature of the majority of the neurons activated during PS had not been characterized. To determine whether these neurons are GABAergic, we combined in situ hybridization of GAD 67 mRNA with immunohistochemical detection of Fos in control, PS deprived and PS hypersomniac rats. We found that 74% of the very large population of Fos-labeled neurons located in the tuberal hypothalamus after PS hypersomnia were GAD-positive. We further demonstrated combining MCH immunohistochemistry and GAD 67 in situ hybridization that 85% of the MCH neurons were also GAD-positive. Finally, based on the number of Fos-ir/GAD + , Fos-ir/ MCH + , and GAD + /MCH + double-labeled neurons counted from three sets of double-staining, we uncovered that around 80% of the large number of the Fos-ir/GAD + neurons located in the tuberal hypothalamus after PS hypersomnia do not contain MCH. Based on these and previous results, we propose that the non-MCH Fos/GABAergic neuronal population could be involved in PS induction and maintenance while the Fos/MCH/GABAergic neurons could be involved in the homeostatic regulation of PS. Further investigations will be needed to corroborate this original hypothesis.
Peptides, 2006
Neurotensin (NT) is a peptide that is widely distributed throughout the brain. NT is involved in ... more Neurotensin (NT) is a peptide that is widely distributed throughout the brain. NT is involved in locomotion, reward, stress and pain modulation, and in the pathophysiology of drug addiction and depression. In its first part this review brings together relevant literature about the neuroanatomy of NT and its receptors. The second part focuses on functional-anatomical interactions between NT, the mesotelencephalic dopamine system and structures targeted by dopaminergic projections. Finally, recent data about the actions of NT in processes underlying behavioral sensitization to psychostimulant drugs and the involvement of NT in the regulation of the hypothalamo-pituitary-adrenal gland axis are considered.
Pediatric Research, 2002
Catecholamine release from the adrenal medulla glands plays a vital role in postnatal adaptation.... more Catecholamine release from the adrenal medulla glands plays a vital role in postnatal adaptation. A number of pathologic situations are characterized by oxygen deficiency. The objective of the present study was to determine the influence of long-term prenatal hypoxia on maturation of the adrenal medulla. Pregnant rats were subjected to hypoxia (10% O 2 ) from the fifth to the 20th d of gestation. The offspring were examined on the 19th d of gestation (E19), the day of birth (P0), and at postnatal (P) day of life P3, P7, P14, P21, and P68. The catecholamine content and activity of tyrosine hydroxylase (TH) in vivo were assayed by HPLC with electrochemical detection. Cellular expression of TH and phenylethanolamine N-methyl transferase was evaluated by protein immunohistochemistry and in situ hybridization of the corresponding mRNA species. Exposure to prenatal hypoxia reduced the epinephrine content of the adrenal medulla on E19, P0, P3, and P7 while increasing the norepinephrine content on E19, P0, and P14. Furthermore, the peak epinephrine to norepinephrine ratio appearing between P7 and P10 in the normoxic offspring was absent in the hypoxic offspring. The in vivo TH activity was increased on P3 and P14 and decreased on P68. The percentage of chromaffin cells in the medulla expressing TH and phenylethanolamine N-methyl transferase was lowered on E19, P0, and P7. TH and phenylethanolamine N-methyl transferase mRNA levels were reduced on P7. Clearly prenatal hypoxia results in major changes in adrenal catecholamine stores and synthesis during the perinatal period, which persist into adulthood. The capacity to cope with postnatal stress might be disturbed as a consequence of prenatal hypoxia. (Pediatr Res 51: 207-214, 2002) Abbreviations DOPA, L-3,4-dihydroxyphenylalanine E, epinephrine E19, d 19 of embryogenesis HPLC-ED, HPLC with electrochemical detection Hx, hypoxic NE, norepinephrine Nx, normoxic PNMT, phenylethanolamine N-methyl transferase P0, day of birth P3, d 3 of postnatal life P7, d 7 of postnatal life P14, d 14 of postnatal life P21, d 21 of postnatal life P68, d 68 of postnatal life TH, tyrosine hydroxylase 11 -OHSD, 11-hydroxysteroid dehydrogenase
Neuroscience Letters, 1989
The existence of GABAergic neurons in the rat suprachiasmatic nucleus (SCN) was demonstrated by t... more The existence of GABAergic neurons in the rat suprachiasmatic nucleus (SCN) was demonstrated by three specific markers; mRNA coding for glutamic acid decarboxylase (GAD) and visualized by in situ hybridization using a 35S-labelled cDNA probe, and GAD protein and GABA were identified by immunocytochemistry using specific antisera. In situ hybridization demonstrated well labelled GAD mRNA positive cells throughout SCN, and GABA and GAD immunoreactive cells showed similar distributions. These results indicate that GABA is a transmitter of a large portion of the SCN neuronal population.
Neuroscience Letters, 1994
In the present study, we examined the regulation of neurotensin receptor following a chronic phar... more In the present study, we examined the regulation of neurotensin receptor following a chronic pharmacological blockade of the neurotensin transmission with a nonpeptide neurotensin receptor antagonist, SR 48692. Our results showed that treatment of the rats for five days with SR 48692, at a dose of 1 mg/kg, i.p., induced an increase of both the number of binding sites for 125I-neurotensin to whole brain membrane homogenates and neurotensin receptor mRNA levels in the ventral mesencephalon. This study brings the first evidence for an in vivo up-regulation of neurotensin receptors following their pharmacological blockade, and suggests that endogenous neurotensin exerts a tonic inhibitory control on neurotensin receptor mRNA levels.
Neuroscience Letters, 1991
Neuromedin N (NN) is a hexapeptide that shares a four amino acid identity with the C-terminus of ... more Neuromedin N (NN) is a hexapeptide that shares a four amino acid identity with the C-terminus of neurotensin (NT) and exhibits NT-like effects in the central nervous system. Both peptides were recently shown to be encoded in the same precursor molecule. By means of specific and sensitive radioimmunoassays, we compared the distribution of immunoreactive NT and NN (iNT and iNN) in micropunched rat brain structures. The data revealed marked regional variations in the ratio of iNT over iNN. For instance, the ratio value was 4.5 in the posterior hypothalamus and 0.8 in the mammillary bodies. Reverse phase HPLC analysis of extracts of several brain regions showed that iNT and iNN coeluted with synthetic NT and NN, respectively. The results suggest that differential processing of the common neurotensin/neuromedin N precursor occurs in various regions of the rat brain.
Neuroscience, 2006
Osmoprotective genes are tonicity-activated genes involved in cellular osmoadaptation to hyperton... more Osmoprotective genes are tonicity-activated genes involved in cellular osmoadaptation to hypertonicity and considered to be regulated by a specific transcription factor called tonicity-responsive enhancer-binding protein (TonEBP). In the brain we had previously established that TonEBP was expressed and tonicity-induced in neurons only. Here we have compared in various brain regions of rats subjected to systemic hypertonicity, the cellular expression of TonEBP through immunocytochemistry and the cellular expression of osmoprotective genes, namely aldose reductase (AR), sodium-dependent myo-inositol transporter (SMIT), betaine/GABA transporter (BGT1) and taurine transporter (TauT), by in situ hybridization using non-radioactive digoxigenin-labeled riboprobes. In neurons where TonEBP was strongly tonicity-induced, AR-mRNA labeling was strongly increased in some subsets (e.g. hippocampus pyramidal cells, cerebellar Purkinje cells and neurons of the hypothalamic magnocellular nuclei) but remained undetectable in some other subsets (e.g. neurons in cerebral cortex). Tonicity-induced AR-mRNA labeling was observed only several hours after the tonicity-induced expression of TonEBP. SMIT-mRNA labeling was tonicity-induced as densely and evenly distributed dots in neuron poor regions (e.g. cerebral cortex layer I and hippocampus stratum lacunosum-moleculare). The tonicity-induced expression of SMIT-mRNA may thus occur in non-neuronal cells, presumably astrocytes, where TonEBP is neither significantly expressed, nor tonicity-induced. In neurons showing a strong tonicity-induced expression of TonEBP, no SMIT-mRNA labeling was observed. BGT1-mRNA and TauT-mRNA labeling could not be detected, even after systemic hypertonicity. The present work reveals large discrepancies between the cellular distribution of the tonicity-induced expression of osmoprotective genes and that of their regulatory transactivator TonEBP. Depending on the cell subsets and the osmoprotective genes, TonEBP may appear insufficient or conversely unnecessary for the tonicity-induced activation of an osmoprotective gene. Altogether our results show that brain cells, even from the same class, activate distinct osmoprotective genes through distinct activation processes to adapt to hypertonicity.
Neuroscience, 2008
5-HT 1A autoreceptors regulate the firing of 5-HT neurons and their release of 5-HT. In previous ... more 5-HT 1A autoreceptors regulate the firing of 5-HT neurons and their release of 5-HT. In previous immuno-electron microscopic studies, we have demonstrated an internalization of 5-HT 1A autoreceptors in the nucleus raphe dorsalis (NRD) of rats, after the acute administration of a single dose o f t h e specific agonist 8-hydroxy-2-(di-n-propylamine)tetralin (8-OH-DPAT) o r o f t h e selective 5-HT reuptake inhibitor, fluoxetine. Twenty-four hours after either treatment, the receptors were back in normal density on the plasma membrane of NRD neurons. Here, we examined the subcellular localization of these receptors and the in vivo binding of the 5-HT 1A radioligand 4,2-(methoxyphenyl)-1-[2-(N-2-pyridinyl)-p-fluorobenzamido]ethylpiperazine labeled with [ 18 F]fluorine ([ 18 F]MPPF)
Neuroscience, 1981
... scand. 64 (suppl. 247), 37-85.GALE K., HONG JS & GUIDOTTI A. (1977) Presence of substance... more ... scand. 64 (suppl. 247), 37-85.GALE K., HONG JS & GUIDOTTI A. (1977) Presence of substance P and GABA in separate striatonigral neurons. BrainRes. ... 11, 249-262.GROVES PM. WILSON CJ, YOUNG SJ & REBEC GV (1975) Self-inhibition by dopaminergic neurons. ...
Neuroscience, 2001
AbstractöThe morphological and physiological substrates that underlie the mutual regulatory inter... more AbstractöThe morphological and physiological substrates that underlie the mutual regulatory interactions of neurotensin and dopamine in the rat mesotelencephalic projections and related structures remain to be fully described. A salient candidate for neurotensinergic e¡ects on the mesotelencephalic dopamine projection is the dense plexus of neurotensin immunoreactive axons that enmeshes the ventral tegmental area and substantia nigra, but the locations of the neurons that give rise to this plexus have not been identi¢ed and its systemic context remains obscure. To address this, Fluoro-Gold and the cholera toxin L subunit, retrogradely transported axonal tracers, were injected into the ventral tegmental area of rats and the brains were processed to demonstrate neurons that contained both retrograde tracer immunoreactivity and a probe against neurotensin/neuromedin N messenger RNA. Substantial numbers of double-labeled neurons were observed in the rostral part of the lateral septum, and in a region centered on the shared boundaries of the bed nucleus of stria terminalis, ventromedial ventral pallidum, diagonal band of Broca, lateral preoptic area and rostral lateral hypothalamus. A few double-labeled neurons were also observed in the dorsal raphe nucleus and adjacent periaqueductal gray. Despite the administration of haloperidol and D-amphetamine to elicit and enhance neurotensin/ neuromedin N messenger RNA expression in striatum, including the nucleus accumbens and olfactory tubercle, no double-labeled neurons were observed there.
Neuroscience, 1983
The distribution of tyrosine hydroxylase-, substance P- and enkephalin-immunoreactive neurons in ... more The distribution of tyrosine hydroxylase-, substance P- and enkephalin-immunoreactive neurons in the cat dorsolateral pons was studied using the indirect immunofluorescence method of Coons. To allow for the visualization of substance P- and enkephalin-immunoreactive cell bodies, colchicine was injected either in the ventricular space or in the cerebral tissue. The distribution of the tyrosine hydroxylase-immunoreactive cell bodies corresponded with the well-known distribution of catecholamine cells in this area of the brain. The observation of adjacent sections treated separately with tyrosine hydroxylase- and enkephalin-antiserum revealed that most catecholaminergic cells contain enkephalin-immunoreactivity. In addition to this catecholamine-enkephalin cell population, a moderate number of substance P-immunoreactive cell bodies was found in dorsolateral pons. The peribrachial nuclei were found to be densely supplied with substance P- and enkephalin-immunoreactive fibers, whereas the medial subdivisions, which contain the majority of the catecholamine cells in the dorsolateral pons, display a moderate number of immunoreactive fibers. These results are suggestive of interactions between peptide-containing and catecholaminergic neurons and also between-peptide-containing and non-catecholamine-containing neurons in the cat dorsolateral pons.
Neuroscience, 1985
Double post-embedding immunolabehng of both tyrosine hydroxylase and glutamate decarboxylase on l... more Double post-embedding immunolabehng of both tyrosine hydroxylase and glutamate decarboxylase on l-pm semi-thin sections allowed the visualization of numerous endings that use y-aminobutyrate as a transmitter apposed to dopaminergic cell bodies in the periventricular-arcuate hypothalamic complex. Up to fifteen glutamate decarboxylase-positive contacts per tyrosine hydroxylasepositive cell profile could be observed. In some favourable planes of section glutamate dccarboxylasepositive endings were also seen in close apposition to proximal dopaminergic dendrites. About 250 tyrosine hydroxylase-positive cell profiles, whose diameter approached the maximum diameter of the dopaminergic cells, were surveyed. An average of 7.4 glutamate decarboxylase-positive contacts were counted on these profiles. From these figures it was estimated that a dopaminergic cell body was contacted on average by 75-175 terminals that use y-aminobutyrate as a transmitter. At the electron-microscopic level, the nature of these contacts was investigated by a method combining radioautographic detection of cell bodies having taken up tritiated dopamine and pre-embedding immunostaining of glutamate decarboxylase containing endings. Glutamate dccarboxylase-positive axon terminals were seen apposed to somatic and dendritic elements. On some favorable planes of section, they were found to be engaged in morphologically defined synaptic complexes of the symmetrical or asymmetrical type. A number of the postsynaptic perikarya were labelled by tritiated dopamine and, in agreement with the light microscopic observations, they were frequently seen in contact with more than one immunopositive ending.