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Pauline Tarot
To cite this version:
Pauline Tarot. Caractérisation anatomo-fonctionnelle des cellules exprimant les récepteurs D2 à la dopamine (D2R) dans la moelle spinale de souris. Sciences agricoles. Université Montpellier, 2019. Français. �NNT : 2019MONTT071�. �tel-02650768�
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En Neurosciences
École doctorale Sciences Chimiques et Biologiques pour la Santé (CBS2)
Unité de recherche CNRS UMR5203 – INSERM U1191
Présentée par Pauline TAROT
Le 9 Décembre 2019
Sous la direction de Emmanuel VALJENT
"
Devant le jury composé de
Lénaic MONCONDUIT, Maître de Conférence, Université Clermont Auvergne Sébastien CARNICELLA, Chargé de Recherche, INSERM
Pascal FOSSAT, Professeur, Université de Bordeaux Cyril RIVAT, Maître de Conférence, Université de Montpellier Alexandre PATTYN, Chargé de Recherche, INSERM
Emmanuel VALJENT, Directeur de Recherche, INSERM
Rapportrice Rapporteur Examinateur Invité Invité Directeur de thèse " "
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Figure 2 | Organisation anatomo-fonctionnelle des circuits somatosensosensoriels ... 21!
Figure 3 | Classification morphologique des interneurones de la lamina II ... 24!
Figure 4 | Classification transcriptomique des interneurones de la corne dorsale superficielle ... 26!
Figure 5 | Proportions des interneurones inhibiteurs de la corne dorsale superficielle appartenant à différentes populations neurochimiques. D’après Boyle et al., 2017 ... 27!
Figure 6 | Proportions des interneurones excitateurs de la corne dorsale superficielle appartenant à différentes populations neurochimiques ... 28!
Figure 7 | Implication du NPY dans la transmission du message nociceptif ... 33!
Figure 8 | Distribution des récepteurs opioïdergiques mu et delta au niveau des circuits spinaux D’après (Wang et al., 2018) ... 35!
Figure 9 | Action des neurones GABAergiques du RVM sur les neurones Enképhaline-positifs de la corne dorsale : facilitation de la douleur mécanique ... 36!
Figure 10| Implication de la 5-HT dans la modulation de la transmission nociceptive au niveau du SNC ... 38!
Figure 11 |Identité génétique, fonction locomotrice et connexions synaptiques des sous-populations d'interneurones ventraux pré-moteurs. D’après Gosgnach et al., 2017 ... 43!
Figure 12 | Représentation schématique des réseaux locomoteurs spinaux ... 44!
Figure 13 | Circuit inter-neuronaux spinaux de la locomotion ... 47!
Figure 14 | Représentation schématique de la machinerie enzymatique d'un neurone dopaminergique ... 50!
Figure 15 | Distribution des noyaux dopaminergiques au sein du SNC ... 51!
Figure 16 | Cellules TH-positives du A11 ... 52!
Figure 17 | Distribution des récepteurs à la dopamine au niveau lombaire ... 59!
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Figure 21 | Distribution des cellules HA au niveau lombaire de la moelle spinale. ... 94!
Figure 22 | Vérification de l'activité du promoteur Cre par injection intra-spinale de virus AAV9- hEF1α-DIO-XFP-InvCherTF ... 95!
Figure 23 | Validation de l'enrichissement du gène Drd2 dans les cellules HA-positives ... 96!
Figure 24 | Les cellules D2R de la moelle spinale expriment le marqueur neuronal NeuN ... 97!
Figure 25 | Les D2R de la moelle spinale ne sont pas exprimés par les cellules gliales ... 98!
Figure 26 | Les D2R spinaux sont exprimés par des neurones excitateurs ... 99!
Figure 27 | Les D2R spinaux sont faiblement exprimés par les interneurones excitateurs PKCγ ... 100!
Figure 28 | Les D2R spinaux sont exprimés par des neurones inhibiteurs ... 101!
Figure 29 | Les D2R spinaux sont exprimés par des neurones inhibiteurs ... 102!
Figure 30 | Les D2R ne sont pas exprimés dans les motoneurones ... 103!
Figure 31 | Distribution des neurones spinaux exprimant les D2R au sein des neurones identifiés par les protéines liant le calcium... 104!
Figure 32 | Distribution des neurones spinaux exprimant les D2R au sein des neurones identifiés par les peptides opioïdergiques ... 106!
Figure 33 | Stratégie d'invalidation des D2R spinaux du segment lombaire ... 107!
Figure 34 | La délétion des D2R au niveau lombaire ... 109!
Figure 35 | La délétion des D2R au niveau lombaire n'altère ni la coordination motrice ni l'apprentissage moteur ... 111!
Figure 36 | La délétion des D2R au niveau lombaire n’altère pas la coordination motrice fine. ... 113!
Figure 37 | Action des psychostimulants sur les neurones monoaminergiques ... 115!
Figure 38 | . Cinétique d’induction de pS32-cFos au niveau du segment lombaire de la moelle spinale en réponse l’administration de d-amphétamine. ... 117!
!`"
protéines liant le calcium ... 119! Figure 41 | Distribution des cellules pS32-cFos positives au sein des neurones GABAergiques, Glycinergiques. ... 121! Figure 42 | Induction de pS32-cFos au niveau du segment lombaire de la moelle spinale en réponse l’administration de psychostimulants. ... 123! Figure 43 | Induction de pS32-cFos au niveau du segment lombaire de la moelle spinale en réponse l’administration de morphine et dizocilpine ... 125! Figure 44 | Induction de pS32-cFos en réponse l’administration d’inhibiteurs sélectifs de la recapture de monoamines ... 127! Figure 45 | Rôle des récepteurs D1 et NMDA dans la régulation de pS32-cFos en réponse l’administration de d-amphétamine ... 129! "
''
" " " " " " " "!q" AACD, Aromatic-L-Amino Décarboxylase
ALT, Anterolateral Tractus ARNm, ARNmessager
ATV, Aire Tegmentale Ventrale BO, Bulbe Olfactif
CB, Calbindine CCK, Cholécystokinin
CGRP, Calcitonin Gene-Related Peptide LTMR, Low Threshold Mechanoreceptor CPF, Cortex Pré-Frontal
CPG, Central Pattern Generator CR, Calrétinine CR, Cellule de Renshaw D1R, Récepteur D1 à la dopamine D2R, Récepteur D2 à la dopamine D3R, Récepteur D3 à la dopamine D4R, Récepteur D4 à la dopamine D5R, Récepteur D5 à la dopamine DA, Dopamine
DAT, Dopaminergic Transporter DBH : Dopamine-Beta-Hydroxylase DC, Dorsal Column
DOR, Delta Opiod Receptor Dyn, Dynorphine
Enk, Enképhaline
GABA, Gamma Amino Butyric Acid Gal, Galanine
GDB, Ganglion De la Base GRP, Gastrin Releasing Peptide
HB9, Basic Helix-loop-helix domain
containing, class B, 9
IaIN, Interneurones Inhibiteurs A IML, Inter-Médio-Latérale IP, Intra-péritonéale IT, Intrathecal
LCN, Lateral Column Nuclei MN, Motoneurones
MOR, Mu Opioid Receptor NA, Noradrénaline
Nacc, Noyaux Accumbens
NET, Noradrenergic Transporter NK1R, Neurokinin 1 receptor NKB, Neurokinine B NMDA, N-méthyl-D-aspartate Npff, Neuropeptide FF NPY, Neuropeptide Y NT, Neurotransmetteur NTS, Neurotensine
ORL, Opioid Receptor-Like PAG, Periaqueducal Grey
PKA, Protéine Kinase dépendante de l’AMPC PKC, Protéine Kinase C PNTM, Phényléthanolamine N-Méthyltransférase PSCD, neurone Post-Synaptique de la Colonne Dorsale PV, Parvalbumine
!t" SCT, Tractus Spinocervicothalamique
SJSR, Syndrome des Jambes Sans Repos SNC, Système Nerveux Central
Vgat, Vesicular GABA Transporter Vglut, Vesicular Glutamate Transporter VMAT2, Vesicular Monoamines Transporter2 " " " " " " " " " " " " " " " " "
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