Neurocentre Magendie


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Doctorat en neurosciences, 2010

Expertise: Relational Memory, Radial maze, Hippocampus, Aging

Sur un modèle du déclin de la mémoire déclarative lié au vieillissement en labyrinthe radiaire chez la souris, mon projet de recherche vise à comprendre les bases cellulaires des associations temporelles essentielles à la formation de la mémoire déclarative dans la sous-région CA1 de l’hippocampe.

7 publication(s) depuis Décembre 2008:

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19/09/2017 | Proc Natl Acad Sci U S A   IF 9.7
Temporal binding function of dorsal CA1 is critical for declarative memory formation.
Sellami A, Al Abed AS, Brayda-Bruno L, Etchamendy N, Valerio S, Oule M, Pantaleon L, Lamothe V, Potier M, Bernard K, Jabourian M, Herry C, Mons N, Piazza PV, Eichenbaum H, Marighetto A

Temporal binding, the process that enables association between discontiguous stimuli in memory, and relational organization, a process that enables the flexibility of declarative memories, are both hippocampus-dependent and decline in aging. However, how these two processes are related in supporting declarative memory formation and how they are compromised in age-related memory loss remain hypothetical. We here identify a causal link between these two features of declarative memory: Temporal binding is a necessary condition for the relational organization of discontiguous events. We demonstrate that the formation of a relational memory is limited by the capability of temporal binding, which depends on dorsal (d)CA1 activity over time intervals and diminishes in aging. Conversely, relational representation is successful even in aged individuals when the demand on temporal binding is minimized, showing that relational/declarative memory per se is not impaired in aging. Thus, bridging temporal intervals by dCA1 activity is a critical foundation of relational representation, and a deterioration of this mechanism is responsible for the age-associated memory impairment.

21/03/2016 | Psychoneuroendocrinology   IF 4.8
Estradiol enhances retention but not organization of hippocampus-dependent memory in intact male mice.
Al Abed AS, Sellami A, Brayda-Bruno L, Lamothe V, Nogues X, Potier M, Bennetau-Pelissero C, Marighetto A

Because estrogens have mostly been studied in gonadectomized females, effects of chronic exposure to environmental estrogens in the general population are underestimated. Estrogens can enhance hippocampus-dependent memory through the modulation of information storage. However, declarative memory, the hippocampus-dependent memory of facts and events, demands more than abilities to retain information. Specifically, memory of repetitive events of everyday life such as 'where I parked' requires abilities to organize/update memories to prevent proactive interference from similar memories of previous 'parking events'. Whether such organizational processes are estrogen-sensitive is unknown. We here studied, in intact young and aged adult mice, drinking-water (1muM) estradiol effects on both retention and organizational components of hippocampus-dependent memory, using a radial-maze task of everyday-like memory. Demand on retention vs organization was manipulated by varying the time-interval separating repetitions of similar events. Estradiol increased performance in young and aged mice under minimized organizational demand, but failed to improve the age-associated memory impairment and diminished performance in young mice under high organizational demand. In fact, estradiol prolonged mnemonic retention of successive events without improving organization abilities, hence resulted in more proactive interference from irrelevant memories. c-Fos imaging of testing-induced brain activations showed that the deterioration of young memory was associated with dentate gyrus dysconnectivity, reminiscent of that seen in aged mice. Our findings support the view that estradiol is promnesic but also reveal that such property can paradoxically impair memory. These findings have important outcomes regarding health issues relative to the impact of environmental estrogens in the general population.

The Drosophila gene fruitless expresses male and female specific transcription factors which are responsible for the generation of male specific neuronal circuitry for courtship behavior. Mutations in this gene may lead to bisexual behavior in males. Bisexual behavior in males also occurs in the absence of the neuropeptide SIFamide. We show here that the SIFamide neurons do not express fruitless. However, when fruitless neurons are made to express RNAi specific for the SIFamide receptor, male flies engage in bisexual behavior, showing that SIFamide acts on fruitless neurons. If neurons expressing a SIFaR-gal4 transgene are killed by the apoptotic protein reaper or when these neurons express SIFamide receptor RNAi, males also show male-male courtship behavior. We next used this transgene to localize neurons that express the SIFamide receptor. Such neurons are ubiquitously present in the central nervous and we also found two neurons in the uterus that project into the central nervous system.

The Drosophila ATP7 copper transporter has sequence homology to the human copper transporters ATP7A and ATP7B, which are defective in Menkes and Wilson disease, respectively. We show here that in Drosophila ATP7 is expressed by many peptidergic neurons. As C-terminal amidation of neuropeptides depends on the copper-containing enzyme PHM, it seemed likely that in the absence of ATP7 the activity of PHM might be compromised. Indeed, inhibition of ATP7 expression by RNAi led to a decrease in mature amidated neuropeptides and the appearance of C-terminally Gly-extended neuropeptides. The strength of this effect differed from one cell type to another; it was very pronounced for AKH and corazonin, but much less so for SIFamide and myosuppressin. Nevertheless, down-regulation of ATP7 specifically in the SIFamide-expressing neurons resulted in male-male courtship behavior.

01/02/2011 | Gen Comp Endocrinol   IF 2.6
Neuroendocrine cells in Drosophila melanogaster producing GPA2/GPB5, a hormone with homology to LH, FSH and TSH.
Sellami A , Agricola HJ , Veenstra JA

Thyrostimulin is a dimer hormone formed from glycoprotein A2 (GPA2) and glycoprotein B5 (GPB5) that activates the TSH receptor in vertebrates. A Drosophila GPA2/GPB5 homolog has recently been characterized. Cells producing this novel hormone were localized by in situ hybridization using both the GPA2 and GPB5 DNA sequences and by making transgenic flies in which the GPB5 promoter drives the expression of gal4. Endocrine cells producing GPA2/GPB5 were found in the abdominal neuromeres and are different from the endocrine cells producing crustacean cardioactive peptide or those making leucokinin. They are also not immunoreactive to antisera to the CRF- or calcitonin-like diuretic hormones. Their axons leave the central nervous system through the segmental nerves and project to the periphery were they likely release GPA2/GPB5 into the hemolymph. As has been described for the leucokinin endocrine cells their axons run over the surface of the abdominal musculature, however, the projection patterns of the leucokinin and GPA2/GPB5 neuroendocrine cells are not identical. The chances of adult eclosion of insects from which the GPA2/GPB5 cells have been genetically ablated or have been made to express GPB5-RNAi are severely compromised, demonstrating the physiological importance of the cells producing this hormone. As the receptor for GPA2/GPB5 stimulates the production of cyclic AMP (cAMP) and is highly expressed in the hindgut, where cAMP stimulates water reabsorption in locusts, it is suggested that GPA2/GPB5 may be an insect anti-diuretic hormone.

We made Drosophila which express the mu opioid receptor under control of UAS in order to inactivate neurons or neuroendocrine cells expressing this receptor with opioid agonists. However, while exposing flies expressing the mu opioid receptor in the SIFamide neurons to opioid agonists was expected to induce male-male courtship behavior, this did not occur. Furthermore, flies which expressed the mu opioid receptor in the AKH or corazonin endocrine cells increased rather than decreased trehalose levels and this was independent of opioid agonists. When the mu opioid receptor is expressed in AKH endocrine cells whole body glycogen also increases, which is no longer the case if the expression of the AKH gene is suppressed by RNAi. It appears that mu opioid receptors expressed in AKH or corazonin endocrine cells are constitutively active and facilitate release of neurohormones. The simultaneous increase in both glycogen and trehalose in these flies suggested that they consumed more food. Indeed, when normally fed males are offered sucrose, those that express this receptor in AKH cells consumed more sucrose, suggesting that AKH increases the motivation to feed. These pharmacological effects of the mu opioid receptor are not limited to neuroendocrine cells; expressing it in the fat body also leads to an increase in trehalose. Thus in Drosophila the mu opioid receptors appear to change the base line activity in the cells in which it is expressed, not unlike to what has been found in transgenic mice expressing receptors activated solely by synthetic ligands with significant constitutive activity.

12/2008 | Cell Tissue Res   IF 2.8
Regulatory peptides in fruit fly midgut.
Veenstra JA , Agricola HJ , Sellami A

Regulatory peptides were immunolocalized in the midgut of the fruit fly Drosophila melanogaster. Endocrine cells were found to produce six different peptides: allatostatins A, B and C, neuropeptide F, diuretic hormone 31, and the tachykinins. Small neuropeptide-F (sNPF) was found in neurons in the hypocerebral ganglion innervating the anterior midgut, whereas pigment-dispersing factor was found in nerves on the most posterior part of the posterior midgut. Neuropeptide-F (NPF)-producing endocrine cells were located in the anterior and middle midgut and in the very first part of the posterior midgut. All NPF endocrine cells also produced tachykinins. Endocrine cells containing diuretic hormone 31 were found in the caudal half of the posterior midgut; these cells also produced tachykinins. Other endocrine cells produced exclusively tachykinins in the anterior and posterior extemities of the midgut. Allatostatin-immunoreactive endocrine cells were present throughout the midgut. Those in the caudal half of the posterior midgut produced allatostatins A, whereas those in the anterior, middle, and first half of the posterior midgut produced allatostatin C. In the middle of the posterior midgut, some endocrine cells produced both allatostatins A and C. Allatostatin-C-immunoreactive endocrine cells were particularly prominent in the first half of the posterior midgut. Allatostatin B/MIP-immunoreactive cells were not consistently found and, when present, were only weakly immunoreactive, forming a subgroup of the allatostatin-C-immunoreactive cells in the posterior midgut. Previous work on Drosophila and other insect species suggested that (FM)RFamide-immunoreactive endocrine cells in the insect midgut could produce NPF, sNPF, myosuppressin, and/or sulfakinins. Using a combination of specific antisera to these peptides and transgenic fly models, we showed that the endocrine cells in the adult Drosophila midgut produced exclusively NPF. Although the Drosophila insulin gene Ilp3 was abundantly expressed in the midgut, Ilp3 was not expressed in endocrine cells, but in midgut muscle.