Axe de recherche neurobiologie cellulaire
Centre de recherche de l'Institut universitaire en santé mentale de Québec
Unité de neurobiologie cellulaire
2601 Chemin de la Canardière, Suite F-6500
Beauport (Québec) G1J 2G3
Tel: (418) 663-5747
FAX : (418) 663-8756
It has been a long-held belief that production of new neurons was exclusive to the embryonic brain. In the past decades, however, much evidence has confirmed the presence of neurogenesis in certain regions of the mature brain. Adult neurogenesis is most prominent in the mammalian forebrain, where neuronal progenitors (originating from stem cells in the subventricular zone - SVZ) course along the rostral migratory stream (RMS) before reaching the olfactory bulb (OB). There, they differentiate into local interneurons (Fig. 1).
The research objectives of our group are:
1. to elucidate the cellular and molecular mechanisms governing adult neurogenesis
2. to employ these mechanisms for cell replacement therapies in animal models of neurodegenerative diseases and stroke
3. to understand the functional role of adult OB neurogenesis
Despite recent progress in the field of adult neurogenesis we are still lacking critical information on the molecular and cellular mechanisms orchestrating this process. We need to understand how to control stem cells proliferation and differentiation into specific cell types, their targeting to particular brain regions and their maturation and integration into neural networks.
To study these mechanisms we use multidisciplinary approaches. We label newly born bulbar interneurons either by intraperitoneal injection of BrdU, a DNA synthesis marker, or by stereotaxic injections of GFP-expressing viruses and cell trackers into the SVZ and RMS. Then, we use a battery of basic molecular biology, cell culture, in situ hybridization and immunohistochemistry tools combined with Ca 2+ -imaging, two-photon and electrophysiological recordings.
Neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's diseases, as well as stroke are characterized by an irreversible loss of chemospecific neurons in distinct brain areas. In that context, adult neurogenesis has raised great expectations since a better understanding of the molecular and cellular mechanisms governing different processes of new neuron generation, fate determination, migration, maturation and integration in the adult brain should contribute to developing new strategies for cell replacement therapies.
We explore whether and how manipulation in the cellular and molecular mechanisms of adult neurogenesis contributes to the structural and functional recovery of damaged areas. We use temporal middle cerebral artery occlusion (tMCAO) as a mouse model for ischemia and MPTP-treated mice as a model for Parkinson disease.
The mammalian olfactory system has a remarkable capability to recognize and discriminate a wide range of odor molecules. This not only provides essential information for animal survival but has also profound effects on their behavior. Interestingly, adult OB receives about 40,000 neuronal precursors every day. This continuous neuronal turnover imposes to the olfactory system an ever-lasting dilemma of preserving normal olfactory information processing despite persistent changes in the topographic and functional odor maps. We would like to understand how basic odor information processing is preserve under these continuously changing conditions and what is the functional role of these new neurons in the adult OB neuronal network.
Canada Research Chair in postnatal neurogenesis
Canadian Foundation for Innovation (CFI)
Natural Science and Engineering Research Council of Canada (NSERC)
Centre de Recherche Universite Laval Robert-Giffard (CRIUSMQ)
Saghatelyan A, Roux P, Migliore M, Rochefort C, Desmaisons D, Charneau P, Shepherd G and Lledo PM. Activity-dependent adjustments of the inhibitory network in the olfactory bulb following early postnatal deprivation Neuron 46: 103-116.
Hack MA, Saghatelyan A (equally contributed), de Chevigny A, Pfeifer A, Ashery-Padan R, Lledo PM and Goetz M. Neuronal fate determinants of adult olfactory bulb neurogenesis Nat. Neurosci.8: 865-872.
Lemasson M, Saghatelyan A, Olivo-Marin JC, and Lledo PM. Neonatal and adult neurogenesis provide two distinct populations of granule cells in the mouse olfactory bulb J. Neurosci. 25: 6816-6825.
Saghatelyan A, de Chevigny A, Schachner M and Lledo PM. Tenascin-R mediates activity-dependent recruitment of neuroblasts in the adult mouse forebrain. Nat. Neurosci. 7: 347-356.
Mechawar N, Saghatelyan A, Grailhe R, Scoriels L, Gheusi G, Gabellec MM, Lledo PM and Changeux JP. Nicotinic receptors regulate the survival of newborn neurons in the adult olfactory bulb. Proc. Natl. Acad. Sci. USA 101: 9822-9826.
Saghatelyan A, Nikonenko A, Sun M, Rolf B, Putthoff P, Kutsche M, Bartsch U, Dityatev A, and Schachner M. Reduced GABAergic transmission and number of hippocampal perisomatic inhibitory synapses in mice deficient in the neural cell adhesion molecule L1.Mol Cell Neurosci. 26: 191-203.
Saghatelyan AK, Snapyan M, Gorissen S, Meigel I, Mosbacher J, Kaupmann K, Bettler B, Kornilov A, Nifant’ev N, Sakanyan V, Schachner M and Dityatev AE Recognition molecule associated carbohydrate inhibits postsynaptic GABAB receptors: a mechanism for homeostatic regulation of GABA release in perisomatic synapses. Mol Cell Neurosci. 24: 271-282.
Senn C, Kutshe M, Saghatelyan AK, Bösl M, Löhler J, Bartsch U, Morellini F and Schachner M Mice deficient for the HNK-1 sulfotransferase show alterations in synaptic efficacy and spatial learning and memory. Mol Cell Neurosci. 20: 712-729.
Saghatelyan AK, Dityatev A, Schmidt S, Schuster T, Bartsch U and Schachner M Reduced perisomatic inhibition, increased excitatory transmission, and impaired long-term potentiation in mice deficient for the extracellular matrix glycoprotein tenascin-R. Mol Cell Neurosci. 17: 226-40.
Saghatelyan AK, Gorissen S, Albert M, Hertlein B, Schachner M and Dityatev AE The extracellular matrix molecule tenascin-R and its HNK-1 carbohydrate modulate perisomatic inhibition and long-term potentiation in the CA1 region of the hippocampus. Eur J Neurosci. 12: 3331-42.
Batueva IV, Buchanan JT, Tsvetkov EA, Sagatelyan AK and Veselkin NPCalcium currents and GABAB receptors in the dorsal sensory cells of the lamprey spinal cord. Neurosci Behav Physiol 29: 67-77.
Batueva IV, Buchanan JT, Tsvetkov EA, Sagatelyan AK and Veselkin NPThe effects of baclofen on calcium channel currents in dorsal sensory cells of the spinal cord in the lamprey.Neurosci Behav Physiol 29: 79-89.
Batueva I, Tsvetkov E, Sagatelyan AK, Buchanan JT, Vesselkin N, Adanina V, Suderevskaya E, Rio JP and Reperant J Physiological and morphological correlates of presynaptic inhibition in primary afferents of the lamprey spinal cord. Neuroscience 88: 975-87.
Sagatelian AK, Suderevskaia EI, Batueva IV, Buchanan JT, Veselkin NP and Tsvetkov EA GABA-activated cloride currents in isolated spinal neurons from lamprey, Lampetra fluviatilis. Zh Evol Biokhim Fiziol 34; 419-29.
Lledo P.M. and Saghatelyan A. Integrating new neurons into the adult olfactory bulb: joining the network, life/death decisions, and the effects of sensory experience. TINS 28: 248-254.
Lledo P.M., Saghatelyan A. and Lemasson M. Inhibitory interneurons in the olfactory bulb - from development to function. The Neuroscientist 10(4): 292-303.
Saghatelyan A, Carleton A, Lagier S, de Chevigny A and Lledo PM Local neurons play key roles in the mammalian olfactory bulb J. Physiol. (Paris) 97: 517-528.
Lledo P.M., Saghatelyan A. and Gheusi G Adult neurogenesis controls excitatory-inhibitory balance in the olfactory bulb. In: Excitatory-Inhibitory balance: synapses, circuits and systems plasticity. Hensch T (ed.), Kluwer Academic Press.