Curieusement, lui qui avait tant parlé de lui-même et surtout tant produit était resté dissimulé ... more Curieusement, lui qui avait tant parlé de lui-même et surtout tant produit était resté dissimulé derrière le rideau de fumée que dressaient ses propos et trop rares étaient ces objets créés par lui que les chercheurs pouvaient lui attribuer avec certitude. Ce n'étaient pas les ...
The supraoptic nucleus receives an abundant gamma-aminobutyric acid (GABA)ergic input which is in... more The supraoptic nucleus receives an abundant gamma-aminobutyric acid (GABA)ergic input which is inhibited by activation of various presynaptic metabotropic receptors. We here analysed the subtypes of voltage-gated Ca2+ channels intervening in the control of transmitter release at these synapses. To address this issue, we tested various specific inhibitors of Ca2+ channels on evoked inhibitory postsynaptic currents (IPSCs). Blocking N- and P-type voltage-gated Ca2+ channels with 1 micromomega-conotoxin-GVIA and 20 nmomega-agatoxin-IVA, respectively, dramatically reduced IPSC amplitude. Q- and L-type Ca2+ channels also contributed to GABAergic transmission, although to a lesser extent, as revealed by applications of 200 nmomega-agatoxin-IVA and of the dihydropyridines nifedipine (10 microm) and nimodipine (10 microm). Evoked IPSCs were insensitive to SNX-482 (300 nm), a blocker of some R-type Ca2+ channels. Analysis of selective blockade by the various antagonists suggested that multiple types of Ca2+ channels synergistically interact to trigger exocytosis at some individual GABA release sites. We next investigated whether inhibition of GABA release in response to the activation of metabotropic glutamate, GABA and adenosine receptors involved the modulation of these presynaptic Ca2+ channels. This was not the case, as the inhibitory actions of selective agonists of these receptors were unaffected by the presence of the different Ca2+ channel antagonists. This finding suggests that these metabotropic receptors modulate GABAergic transmission through a different mechanism, downstream of Ca2+ entry in the terminals, or upstream through the activation of K+ channels.
The present ultrastructural study analysed the distribution of glutamatergic synapses on oxytocin... more The present ultrastructural study analysed the distribution of glutamatergic synapses on oxytocin- and vasopressin-secreting neurons in the rat supraoptic nucleus (SON) after post-embedding immunogold labelling for glutamate immunoreactivity, visible over synaptic-like vesicles, mitochondria and synaptic densities. Double labelling for glutamate and GABA showed that putative glutamatergic terminals were distinct from GABAergic terminals. In ultrathin sections stained for glutamate and either oxytocin or vasopressin, the proportion of glutamatergic synapses was similar on oxytocinergic and vasopressinergic somata in virgin rats under basal conditions of peptide release as well as in lactating rats, in which oxytocin secretion is enhanced. Cross-sectional soma areas were significantly increased in lactating rats: oxytocinergic profiles were, on average, approximately 40% larger than in virgin rats. However, the incidence of axo-somatic glutamatergic synapses (assessed as mean number of synapses per 100 microm of plasmalemma or proportion of somatic surface apposed to synaptic active zones) did not diminish, indicating that there was a compensatory increase of synapses during lactation. Also, we found an increase in the number of glutamatergic terminals making synaptic contact simultaneously onto two or more oxytocinergic elements in the same plane of section. Our observations therefore indicate that SON oxytocinergic and vasopressinergic neurons are innervated to a similar extent by a relatively large proportion of glutamatergic synapses. They reveal, moreover, that glutamatergic afferents participate in the lactation-induced synaptic plasticity of the oxytocinergic system.
Advances in Experimental Medicine and Biology, Feb 1, 1999
A striking example of the capacity of adult astrocytes to undergo reversible morphological change... more A striking example of the capacity of adult astrocytes to undergo reversible morphological changes in response to stimuli which enhance neuronal activity is offered by astrocytes of the adult hypothalamo-neurohypophysial system (HNS). The HNS is composed of magnocellular neurons secreting the neurohormones oxytocin and vasopressin from axon terminals in the neurohypophysis. Upon activation of HNS secretion, glial coverage of oxytocin neurons significantly diminishes and their surfaces become extensively juxtaposed. These glial changes are invariably accompanied by structural synaptic remodelling resulting in increased numbers of GABAergic, glutamatergic, and noradrenergic afferents. In the neurohypophysis, they result in an enhanced neurohemal contact area. HNS glia in the adult continue to display "embryonic" features that may allow such activity-dependent structural plasticity. For example, supraoptic astrocytes display a radial glia-like morphology and continue to express vimentin, together with GFAP. All HNS astrocytes secrete extracellular matrix glycoproteins, like tenascin-C; they also express high levels of polysialylated NCAM or PSA-NCAM and the glycoprotein F3, molecules considered essential for neuronal-glial interactions in the developing and lesioned CNS. HNS expression of most of these proteins does not visibly vary under different conditions of neurohormone secretion. We consider them as permissive factors, therefore, allowing HNS cells to undergo remodeling whenever the proper stimuli intervene. In the hypothalamic nuclei, one such stimulus is oxytocin itself which, in synergy with steroids, can induce neuronal-glial remodelling; adrenaline does so in the neurohypophysis.
Proceedings of the Royal Society of London. Series B, Biological sciences, 1977
ABSTRACT Antidromically identified neurosecretory cells of the paraventricular (p.v.) and supraop... more ABSTRACT Antidromically identified neurosecretory cells of the paraventricular (p.v.) and supraoptic (s.o.) nuclei of the hypothalamus were recorded in lactating rats under urethane anaesthesia during reflex milk ejection (m.e.) and haemorrhage. Eighty one p.v. and s.o. neurones were studied. Their background firing rates ranged from < 0.1 to 6.3 spikes/s and three distinct patterns of activity were encountered: slow irregular (73%), fast continuous (10%) and phasic (17%). Forty units (49%) displayed a brief (2-4 s) high-frequency discharge (30-60 spikes/s) correlated with suckling-induced m.e., and these were classified as m.e. (oxytocin-secreting) neurones. The remainder of the cells showed no activation at this time and were classified as non-m.e. neurones. Ten m.e. neurones tested through haemorrhage (5 ml of blood) showed a gradual acceleration of firing rates, reaching a maximum of 3.7 ± 0.7 spikes/s (mean ± s.e.) about 20 min after blood withdrawal. The firing pattern of the m.e. neurones therefore changed from a slow irregular to a fast continuous type. By contrast, 11 non-m.e. neurones tested with the same procedure showed a rapid activation reaching a maximum of 6.4 ± 0.6 spikes/s by the fourth minute. Non-m.e. neurones which were initially of the slow irregular type, first became fast continuous and later evolved into a highly characteristic phasic pattern of activity which was never induced in the m.e. neurones. After the blood was replaced, all the cells returned to their original firing pattern. In a parallel series of experiments, plasma samples taken 5 and 25 min after haemorrhage showed a ten-fold elevation in antidiuretic activity. A slight but non-significant increase in m.e. activity was also observed. Thus p.v. and s.o. neurosecretory cells may be electrophysically differentiated into two functionally distinct populations: (1) oxytocin releasing neurones which show a high-frequency discharge before m.e. induced by suckling, and (2) vasopressin-releasing neurones which adopt a phasic pattern of firing during vasopressin release induced by haemorrhage. We suggest that the rate of vasopressin secretion into the circulation largely depends on the proportion of vasopressin neurones firing phasically, their firing rates within the phases and the duration and degree of synchronization of the phases.
Advances in experimental medicine and biology, 1999
A striking example of the capacity of adult astrocytes to undergo reversible morphological change... more A striking example of the capacity of adult astrocytes to undergo reversible morphological changes in response to stimuli which enhance neuronal activity is offered by astrocytes of the adult hypothalamo-neurohypophysial system (HNS). The HNS is composed of magnocellular neurons secreting the neurohormones oxytocin and vasopressin from axon terminals in the neurohypophysis. Upon activation of HNS secretion, glial coverage of oxytocin neurons significantly diminishes and their surfaces become extensively juxtaposed. These glial changes are invariably accompanied by structural synaptic remodelling resulting in increased numbers of GABAergic, glutamatergic, and noradrenergic afferents. In the neurohypophysis, they result in an enhanced neurohemal contact area. HNS glia in the adult continue to display "embryonic" features that may allow such activity-dependent structural plasticity. For example, supraoptic astrocytes display a radial glia-like morphology and continue to expre...
The Journal of neuroscience : the official journal of the Society for Neuroscience, 1999
Polysialic acid (PSA) on the extracellular domain of the neural cell adhesion molecule (NCAM) red... more Polysialic acid (PSA) on the extracellular domain of the neural cell adhesion molecule (NCAM) reduces cell adhesion and is considered an important regulator of cell surface interactions. The hypothalamo-neurohypophysial system (HNS), whose glia, neurons, and synapses undergo striking, reversible morphological changes in response to physiological stimulation, expresses high levels of PSA-NCAM throughout life. Light and electron microscopic immunocytochemistry in normal rats and rats in which cell transport was blocked with colchicine showed that PSA-NCAM is expressed in both HNS neurons and glia, particularly at the level of astrocytic processes that envelop neuronal profiles and can undergo remodeling. Moreover, we confirmed that the overall levels of PSA-NCAM were not greatly altered by stimulation (lactation and chronic salt ingestion). Nevertheless, PSA is essential to morphological plasticity. Using comparative ultrastructural analysis, we found that, after specific enzymatic re...
The Journal of neuroscience : the official journal of the Society for Neuroscience, 1998
During lactation and parturition, magnocellular oxytocin (OT) neurons display a characteristic bu... more During lactation and parturition, magnocellular oxytocin (OT) neurons display a characteristic bursting electrical activity responsible for pulsatile OT release. We investigated this activity using hypothalamic organotypic slice cultures enriched in magnocellular OT neurons. As shown here, the neurons are functional and actively secrete amidated OT into the cultures. Intracellular recordings were made from 23 spontaneously bursting and 28 slow irregular neurons, all identified as oxytocinergic with biocytin and immunocytochemistry. The bursting electrical activity was similar to that described in vivo and was characterized by bursts of action potentials (20.1 +/- 4.3 Hz) lasting approximately 6 sec, over an irregular background activity. OT (0.1-1 microM), added to the medium, increased burst frequency, reducing interburst intervals by 70%. The peptide also triggered bursting in 27% of nonbursting neurons. These effects were mimicked by the oxytocin receptor (OTR) agonist [Thr4, Gly...
1. The adult hypothalamoneurohypophysial system (HNS) undergoes reversible morphological changes ... more 1. The adult hypothalamoneurohypophysial system (HNS) undergoes reversible morphological changes in response to physiological stimulation. 2. In the hypothalamus, stimulation of neurohormone secretion results in reduced astrocytic coverage of oxytocinergic somata and dendrites so that their surfaces become directly juxtaposed. Concurrently, there is a significant increase in the number of GABAergic, glutamatergic. and noradrenergic synapses impinging on the neurons. 3. In the neurohypophysis, stimulation induces retraction of pituicyte processes from the perivascular area and enlargement and multiplication of neurosecretory terminals. 4. These neuronal-glial and synaptic changes are reversible with cessation of stimulation, thus rendering the HNS an excellent model to study physiologically linked structural neuronal plasticity in the adult CNS. 5. We still do not know the cellular mechanisms and factors underlying such plasticity. Recent studies indicate, however, that the adult HNS...
Curieusement, lui qui avait tant parlé de lui-même et surtout tant produit était resté dissimulé ... more Curieusement, lui qui avait tant parlé de lui-même et surtout tant produit était resté dissimulé derrière le rideau de fumée que dressaient ses propos et trop rares étaient ces objets créés par lui que les chercheurs pouvaient lui attribuer avec certitude. Ce n'étaient pas les ...
The supraoptic nucleus receives an abundant gamma-aminobutyric acid (GABA)ergic input which is in... more The supraoptic nucleus receives an abundant gamma-aminobutyric acid (GABA)ergic input which is inhibited by activation of various presynaptic metabotropic receptors. We here analysed the subtypes of voltage-gated Ca2+ channels intervening in the control of transmitter release at these synapses. To address this issue, we tested various specific inhibitors of Ca2+ channels on evoked inhibitory postsynaptic currents (IPSCs). Blocking N- and P-type voltage-gated Ca2+ channels with 1 micromomega-conotoxin-GVIA and 20 nmomega-agatoxin-IVA, respectively, dramatically reduced IPSC amplitude. Q- and L-type Ca2+ channels also contributed to GABAergic transmission, although to a lesser extent, as revealed by applications of 200 nmomega-agatoxin-IVA and of the dihydropyridines nifedipine (10 microm) and nimodipine (10 microm). Evoked IPSCs were insensitive to SNX-482 (300 nm), a blocker of some R-type Ca2+ channels. Analysis of selective blockade by the various antagonists suggested that multiple types of Ca2+ channels synergistically interact to trigger exocytosis at some individual GABA release sites. We next investigated whether inhibition of GABA release in response to the activation of metabotropic glutamate, GABA and adenosine receptors involved the modulation of these presynaptic Ca2+ channels. This was not the case, as the inhibitory actions of selective agonists of these receptors were unaffected by the presence of the different Ca2+ channel antagonists. This finding suggests that these metabotropic receptors modulate GABAergic transmission through a different mechanism, downstream of Ca2+ entry in the terminals, or upstream through the activation of K+ channels.
The present ultrastructural study analysed the distribution of glutamatergic synapses on oxytocin... more The present ultrastructural study analysed the distribution of glutamatergic synapses on oxytocin- and vasopressin-secreting neurons in the rat supraoptic nucleus (SON) after post-embedding immunogold labelling for glutamate immunoreactivity, visible over synaptic-like vesicles, mitochondria and synaptic densities. Double labelling for glutamate and GABA showed that putative glutamatergic terminals were distinct from GABAergic terminals. In ultrathin sections stained for glutamate and either oxytocin or vasopressin, the proportion of glutamatergic synapses was similar on oxytocinergic and vasopressinergic somata in virgin rats under basal conditions of peptide release as well as in lactating rats, in which oxytocin secretion is enhanced. Cross-sectional soma areas were significantly increased in lactating rats: oxytocinergic profiles were, on average, approximately 40% larger than in virgin rats. However, the incidence of axo-somatic glutamatergic synapses (assessed as mean number of synapses per 100 microm of plasmalemma or proportion of somatic surface apposed to synaptic active zones) did not diminish, indicating that there was a compensatory increase of synapses during lactation. Also, we found an increase in the number of glutamatergic terminals making synaptic contact simultaneously onto two or more oxytocinergic elements in the same plane of section. Our observations therefore indicate that SON oxytocinergic and vasopressinergic neurons are innervated to a similar extent by a relatively large proportion of glutamatergic synapses. They reveal, moreover, that glutamatergic afferents participate in the lactation-induced synaptic plasticity of the oxytocinergic system.
Advances in Experimental Medicine and Biology, Feb 1, 1999
A striking example of the capacity of adult astrocytes to undergo reversible morphological change... more A striking example of the capacity of adult astrocytes to undergo reversible morphological changes in response to stimuli which enhance neuronal activity is offered by astrocytes of the adult hypothalamo-neurohypophysial system (HNS). The HNS is composed of magnocellular neurons secreting the neurohormones oxytocin and vasopressin from axon terminals in the neurohypophysis. Upon activation of HNS secretion, glial coverage of oxytocin neurons significantly diminishes and their surfaces become extensively juxtaposed. These glial changes are invariably accompanied by structural synaptic remodelling resulting in increased numbers of GABAergic, glutamatergic, and noradrenergic afferents. In the neurohypophysis, they result in an enhanced neurohemal contact area. HNS glia in the adult continue to display "embryonic" features that may allow such activity-dependent structural plasticity. For example, supraoptic astrocytes display a radial glia-like morphology and continue to express vimentin, together with GFAP. All HNS astrocytes secrete extracellular matrix glycoproteins, like tenascin-C; they also express high levels of polysialylated NCAM or PSA-NCAM and the glycoprotein F3, molecules considered essential for neuronal-glial interactions in the developing and lesioned CNS. HNS expression of most of these proteins does not visibly vary under different conditions of neurohormone secretion. We consider them as permissive factors, therefore, allowing HNS cells to undergo remodeling whenever the proper stimuli intervene. In the hypothalamic nuclei, one such stimulus is oxytocin itself which, in synergy with steroids, can induce neuronal-glial remodelling; adrenaline does so in the neurohypophysis.
Proceedings of the Royal Society of London. Series B, Biological sciences, 1977
ABSTRACT Antidromically identified neurosecretory cells of the paraventricular (p.v.) and supraop... more ABSTRACT Antidromically identified neurosecretory cells of the paraventricular (p.v.) and supraoptic (s.o.) nuclei of the hypothalamus were recorded in lactating rats under urethane anaesthesia during reflex milk ejection (m.e.) and haemorrhage. Eighty one p.v. and s.o. neurones were studied. Their background firing rates ranged from < 0.1 to 6.3 spikes/s and three distinct patterns of activity were encountered: slow irregular (73%), fast continuous (10%) and phasic (17%). Forty units (49%) displayed a brief (2-4 s) high-frequency discharge (30-60 spikes/s) correlated with suckling-induced m.e., and these were classified as m.e. (oxytocin-secreting) neurones. The remainder of the cells showed no activation at this time and were classified as non-m.e. neurones. Ten m.e. neurones tested through haemorrhage (5 ml of blood) showed a gradual acceleration of firing rates, reaching a maximum of 3.7 ± 0.7 spikes/s (mean ± s.e.) about 20 min after blood withdrawal. The firing pattern of the m.e. neurones therefore changed from a slow irregular to a fast continuous type. By contrast, 11 non-m.e. neurones tested with the same procedure showed a rapid activation reaching a maximum of 6.4 ± 0.6 spikes/s by the fourth minute. Non-m.e. neurones which were initially of the slow irregular type, first became fast continuous and later evolved into a highly characteristic phasic pattern of activity which was never induced in the m.e. neurones. After the blood was replaced, all the cells returned to their original firing pattern. In a parallel series of experiments, plasma samples taken 5 and 25 min after haemorrhage showed a ten-fold elevation in antidiuretic activity. A slight but non-significant increase in m.e. activity was also observed. Thus p.v. and s.o. neurosecretory cells may be electrophysically differentiated into two functionally distinct populations: (1) oxytocin releasing neurones which show a high-frequency discharge before m.e. induced by suckling, and (2) vasopressin-releasing neurones which adopt a phasic pattern of firing during vasopressin release induced by haemorrhage. We suggest that the rate of vasopressin secretion into the circulation largely depends on the proportion of vasopressin neurones firing phasically, their firing rates within the phases and the duration and degree of synchronization of the phases.
Advances in experimental medicine and biology, 1999
A striking example of the capacity of adult astrocytes to undergo reversible morphological change... more A striking example of the capacity of adult astrocytes to undergo reversible morphological changes in response to stimuli which enhance neuronal activity is offered by astrocytes of the adult hypothalamo-neurohypophysial system (HNS). The HNS is composed of magnocellular neurons secreting the neurohormones oxytocin and vasopressin from axon terminals in the neurohypophysis. Upon activation of HNS secretion, glial coverage of oxytocin neurons significantly diminishes and their surfaces become extensively juxtaposed. These glial changes are invariably accompanied by structural synaptic remodelling resulting in increased numbers of GABAergic, glutamatergic, and noradrenergic afferents. In the neurohypophysis, they result in an enhanced neurohemal contact area. HNS glia in the adult continue to display "embryonic" features that may allow such activity-dependent structural plasticity. For example, supraoptic astrocytes display a radial glia-like morphology and continue to expre...
The Journal of neuroscience : the official journal of the Society for Neuroscience, 1999
Polysialic acid (PSA) on the extracellular domain of the neural cell adhesion molecule (NCAM) red... more Polysialic acid (PSA) on the extracellular domain of the neural cell adhesion molecule (NCAM) reduces cell adhesion and is considered an important regulator of cell surface interactions. The hypothalamo-neurohypophysial system (HNS), whose glia, neurons, and synapses undergo striking, reversible morphological changes in response to physiological stimulation, expresses high levels of PSA-NCAM throughout life. Light and electron microscopic immunocytochemistry in normal rats and rats in which cell transport was blocked with colchicine showed that PSA-NCAM is expressed in both HNS neurons and glia, particularly at the level of astrocytic processes that envelop neuronal profiles and can undergo remodeling. Moreover, we confirmed that the overall levels of PSA-NCAM were not greatly altered by stimulation (lactation and chronic salt ingestion). Nevertheless, PSA is essential to morphological plasticity. Using comparative ultrastructural analysis, we found that, after specific enzymatic re...
The Journal of neuroscience : the official journal of the Society for Neuroscience, 1998
During lactation and parturition, magnocellular oxytocin (OT) neurons display a characteristic bu... more During lactation and parturition, magnocellular oxytocin (OT) neurons display a characteristic bursting electrical activity responsible for pulsatile OT release. We investigated this activity using hypothalamic organotypic slice cultures enriched in magnocellular OT neurons. As shown here, the neurons are functional and actively secrete amidated OT into the cultures. Intracellular recordings were made from 23 spontaneously bursting and 28 slow irregular neurons, all identified as oxytocinergic with biocytin and immunocytochemistry. The bursting electrical activity was similar to that described in vivo and was characterized by bursts of action potentials (20.1 +/- 4.3 Hz) lasting approximately 6 sec, over an irregular background activity. OT (0.1-1 microM), added to the medium, increased burst frequency, reducing interburst intervals by 70%. The peptide also triggered bursting in 27% of nonbursting neurons. These effects were mimicked by the oxytocin receptor (OTR) agonist [Thr4, Gly...
1. The adult hypothalamoneurohypophysial system (HNS) undergoes reversible morphological changes ... more 1. The adult hypothalamoneurohypophysial system (HNS) undergoes reversible morphological changes in response to physiological stimulation. 2. In the hypothalamus, stimulation of neurohormone secretion results in reduced astrocytic coverage of oxytocinergic somata and dendrites so that their surfaces become directly juxtaposed. Concurrently, there is a significant increase in the number of GABAergic, glutamatergic. and noradrenergic synapses impinging on the neurons. 3. In the neurohypophysis, stimulation induces retraction of pituicyte processes from the perivascular area and enlargement and multiplication of neurosecretory terminals. 4. These neuronal-glial and synaptic changes are reversible with cessation of stimulation, thus rendering the HNS an excellent model to study physiologically linked structural neuronal plasticity in the adult CNS. 5. We still do not know the cellular mechanisms and factors underlying such plasticity. Recent studies indicate, however, that the adult HNS...
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Papers by Dominique Poulain