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Control of Adult-Born Neuron Production by Converging GABA and Glutamate Signals

  • Jean-Claude Platel
  • Angélique Bordey

Abstract

The production of adult-born neuron is an ongoing process ­accounting ∼10,000 immature neurons migrating to the olfactory bulb every day. This high turnover rate necessitates profound control mechanisms converging onto neural progenitors and neuroblasts to achieve adequate adult-born neuron production. Here, we elaborate on a novel epigenetic control of adult neurogenesis via highly coordinated nonsynaptic cell–cell signaling. This communication engages the neurotransmitters GABA and glutamate whose extracellular concentrations depend on neuroblast number and high affinity uptake systems in neural stem cells. Neuroblasts release GABA providing a negative feedback control of stem cell proliferation and instructing them on the size of the neuroblast pool. Recent findings show an unexpected mosaic expression of glutamate receptors leading to calcium elevations in migrating neuroblasts and differential role on their development. Remarkably, stem cells act as lighthouses releasing glutamate onto neuroblast sailing by, thus providing migratory, survival, and proliferative cues. Finally, we propose that the timing of neurotransmitter release and their spatial diffusion will determine the convergent co-activation of neuroblasts and stem cells, and provide a steady-state level of neuron production. Upon external impact or injury this signaling may adjust to a new steady-state level, thus providing nonsynaptic scaling of neuroblast production.

Keywords

NMDA Receptor Glutamate Receptor Olfactory Bulb GABAA Receptor Patch Clamp Recording 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This work was supported by grants from the National Institute of Health (NS048256 and DC007681, A.B.) and Yale Brown-Coxe fellowship (J-C.P.).

References

  1. Andang M, Hjerling-Leffler J, Moliner A, Lundgren TK, Castelo-Branco G, Nanou E, Pozas E, Bryja V, Halliez S, Nishimaru H, Wilbertz J, Arenas E, Koltzenburg M, Charnay P, El Manira A, Ibanez CF, Ernfors P (2008) Histone H2AX-dependent GABA(A) receptor regulation of stem cell proliferation. Nature 451:460–464.PubMedCrossRefGoogle Scholar
  2. Bettler B, Mulle C (1995) Review: neurotransmitter receptors. II. AMPA and kainate receptors. Neuropharmacology 34:123–139.PubMedCrossRefGoogle Scholar
  3. Bolteus AJ, Bordey A (2004) GABA release and uptake regulate neuronal precursor migration in the postnatal subventricular zone. J Neurosci 24:7623–7631.PubMedCrossRefGoogle Scholar
  4. Bordey A (2006) Adult neurogenesis: basic concepts of signaling. Cell Cycle 5:722–728.PubMedCrossRefGoogle Scholar
  5. Bordey A (2007) Enigmatic GABAergic networks in adult neurogenic zones. Brain Res Brain Res Rev 53:124–134.CrossRefGoogle Scholar
  6. Chebib M, Johnston GA (1999) The ‘ABC’ of GABA receptors: a brief review. Clin Exp Pharmacol Physiol 26:937–940.PubMedCrossRefGoogle Scholar
  7. Coutinho V, Knopfel T (2002) Metabotropic glutamate receptors: electrical and chemical signaling properties. Neuroscientist 8:551–561.PubMedCrossRefGoogle Scholar
  8. Curtis MA, Kam M, Nannmark U, Anderson MF, Axell MZ, Wikkelso C, Holtas S, Roon-Mom WM, Bjork-Eriksson T, Nordborg C, Frisen J, Dragunow M, Faull RL, Eriksson PS (2007) Human neuroblasts migrate to the olfactory bulb via a lateral ventricular extension. Science 315:1243–1249.PubMedCrossRefGoogle Scholar
  9. Di Giorgi-Gerevini V, Melchiorri D, Battaglia G, Ricci-Vitiani L, Ciceroni C, Busceti CL, Biagioni F, Iacovelli L, Canudas AM, Parati E, De Maria R, Nicoletti F (2005) Endogenous activation of metabotropic glutamate receptors supports the proliferation and survival of neural progenitor cells. Cell Death Differ 12:1124–1133.PubMedCrossRefGoogle Scholar
  10. Doetsch F, Garcia-Verdugo JM, Alvarez-Buylla A (1997) Cellular composition and three-dimensional organization of the subventricular germinal zone in the adult mammalian brain. J Neurosci 17:5046–5061.PubMedGoogle Scholar
  11. Doetsch F, Garcia-Verdugo JM, Alvarez-Buylla A (1999) Regeneration of a germinal layer in the adult mammalian brain. Proc Natl Acad Sci USA 96:11619–11624.PubMedCrossRefGoogle Scholar
  12. Gascon E, Dayer AG, Sauvain MO, Potter G, Jenny B, De Roo M, Zgraggen E, Demaurex N, Muller D, Kiss JZ (2006) GABA regulates dendritic growth by stabilizing lamellipodia in newly generated interneurons of the olfactory bulb. J Neurosci 26:12956–12966.PubMedCrossRefGoogle Scholar
  13. Ge S, Pradhan DA, Ming GL, Song H (2007) GABA sets the tempo for activity-dependent adult neurogenesis. Trends Neurosci 30:1–8.PubMedCrossRefGoogle Scholar
  14. Lerma J, Paternain AV, Rodriguez-Moreno A, Lopez-Garcia JC (2001) Molecular physiology of kainate receptors. Physiol Rev 81:971–998.PubMedGoogle Scholar
  15. Liu X, Wang Q, Haydar TF, Bordey A (2005) Nonsynaptic GABA signaling in postnatal subventricular zone controls proliferation of GFAP-expressing progenitors. Nat Neurosci 8:1179–1187.PubMedCrossRefGoogle Scholar
  16. Liu X, Bolteus AJ, Balkin DM, Henschel O, Bordey A (2006) GFAP-expressing cells in the postnatal subventricular zone display a unique glial phenotype intermediate between radial glia and astrocytes. Glia 54:394–410.PubMedCrossRefGoogle Scholar
  17. Lledo PM, Alonso M, Grubb MS (2006) Adult neurogenesis and functional plasticity in neuronal circuits. Nat Rev Neurosci 7:179–193.PubMedCrossRefGoogle Scholar
  18. Mak DO, McBride S, Foskett JK (1998) Inositol 1,4,5-trisphosphate [correction of tris-phosphate] activation of inositol trisphosphate [correction of tris-phosphate] receptor Ca2+ channel by ligand tuning of Ca2+ inhibition. Proc Natl Acad Sci USA 95:15821–15825.PubMedCrossRefGoogle Scholar
  19. Merkle FT, Mirzadeh Z, Alvarez-Buylla A (2007) Mosaic organization of neural stem cells in the adult brain. Science 317:381–384.PubMedCrossRefGoogle Scholar
  20. Nguyen L, Malgrange B, Breuskin I, Bettendorff L, Moonen G, Belachew S, Rigo JM (2003) Autocrine/paracrine activation of the GABA(A) receptor inhibits the proliferation of neurogenic polysialylated neural cell adhesion molecule-positive (PSA-NCAM+) precursor cells from postnatal striatum. J Neurosci 23:3278–3294.PubMedGoogle Scholar
  21. Pathania M, Yan LD, Bordey A (2010) A symphony of signals conduct early and late stages of adult neurogenesis. Neuropharmacology 58:865–876.PubMedCrossRefGoogle Scholar
  22. Pinheiro P, Mulle C (2006) Kainate receptors. Cell Tissue Res 326:457–482.PubMedCrossRefGoogle Scholar
  23. Platel JC, Lacar B, Bordey A (2007) GABA and glutamate signaling: homeostatic control of adult forebrain neurogenesis. J Mol Histol 38:602–610.PubMedGoogle Scholar
  24. Platel J, Heintz T, Young S, Gordon V, Bordey A (2008) Tonic activation of GLUK5 kainate receptors decreases neuroblast migration in a whole mount preparation of the subventricular zone. J Physiol (Lond) 586:3783–3793.CrossRefGoogle Scholar
  25. Platel JC, Dave KA, Gordon V, Lacar B, Rubio ME, Bordey A (2010) NMDA receptors activated by subventricular zone astrocytic glutamate are critical for neuroblast survival prior to entering a synaptic network. Neuron 65:859–872.PubMedCrossRefGoogle Scholar
  26. Sanai N, Tramontin AD, Quinones-Hinojosa A, Barbaro NM, Gupta N, Kunwar S, Lawton MT, McDermott MW, Parsa AT, Manuel-Garcia VJ, Berger MS, Alvarez-Buylla A (2004) Unique astrocyte ribbon in adult human brain contains neural stem cells but lacks chain migration. Nature 427:740–744.PubMedCrossRefGoogle Scholar
  27. Schlett K (2006) Glutamate as a modulator of embryonic and adult neurogenesis. Curr Top Med Chem 6:949–960.PubMedCrossRefGoogle Scholar
  28. Stewart RR, Hoge GJ, Zigova T, Luskin MB (2002) Neural progenitor cells of the neonatal rat anterior subventricular zone express functional GABA(A) receptors. J Neurobiol 50:305–322.PubMedCrossRefGoogle Scholar
  29. Wang DD, Krueger DD, Bordey A (2003a) Biophysical properties and ionic signature of neuronal progenitors of the postnatal subventricular zone in situ. J Neurophysiol 90:2291–2302.PubMedCrossRefGoogle Scholar
  30. Wang DD, Krueger DD, Bordey A (2003b) GABA depolarizes neuronal progenitors of the postnatal subventricular zone via GABAA receptor activation. J Physiol (Lond) 550:785–800.CrossRefGoogle Scholar
  31. Young SZ, Platel JC, Nielsen JV, Jensen NA, Bordey A (2010) GABA(A) increases calcium in subventricular zone astrocyte-like cells through L- and T-type voltage-gated calcium channels. Front Cell Neurosci 4:8.PubMedGoogle Scholar

Copyright information

© Springer 2011

Authors and Affiliations

  1. 1.Department of NeurosurgeryYale University School of MedicineNew HavenUSA
  2. 2.Department of Cellular and Molecular PhysiologyYale University School of MedicineNew HavenUSA

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