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    Carlos Lois MD, PhD

    TitleAssociate Professor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentNeurobiology
    AddressUniversity of Massachusetts Medical School
    364 Plantation Street, LRB
    Worcester MA 01605
    Phone508-856-1004
      Other Positions
      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentNeuroscience

        Overview 
        Narrative

        Assembly of neuronal circuits, neuronal integration, and the cellular mechanisms of behavior

        Our laboratory is interested in the assembly of neuronal circuits and the mechanisms by which brain circuits give rise to behavior. We focus on the process of neuron addition into the brain of vertebrates, and seek to understand how new neurons integrate into the circuits of the adult brain, and their role in information processing and storage. To address these questions our laboratory develops new technologies to genetically manipulate the development and biophysical properties of neurons. To investigate how behavior arises from the activity of neurons in brain circuits, we are generating transgenic songbirds to manipulate key genes involved in the assembly of circuits that mediate vocal learning behavior.

        Research Summary

        Most neurons in the brain are born before birth and are never replaced. In contrast, certain populations of neurons are continuously replaced throughout the life of the animal. Do neurons acquired in adult life participate in a special form of memory storage that requires the replacement of old neurons? In mammals, neuronal replacement occurs at high levels in two brain areas be involved in olfactory perception and spatial memory. In songbirds, the capacity to learn their songs varies during adult life, and this variation is correlated to radical structural changes in the brain nuclei controlling song, which include massive neuronal replacement. Recently we have developed several new tools that allow us to genetically control the function of neurons. By using these techniques we are manipulating the birth, death, and electrical function of newly generated neurons in the brain of behaving animals, both in the olfactory system of mice, and in the song system of songbirds.

        Regulation of neuronal integration into brain circuits.

        The brain of adult vertebrates harbors a population of neuronal stem cells that continues to proliferate throughout the life of the animal, and whose progeny migrate through the brain, differentiate into neurons, and   establish synaptic contacts with other neurons in the circuit. We are interested in understanding the cellular and molecular mechanisms that control the integration of these neurons into neuronal circuits. We are currently testing the hypothesis that synaptic input into newly born adult neurons guides the integration of these cells into existing circuits. In addition, we are investigating the mechanisms that neurons use to adapt their intrinsic and synaptic properties as they integrate into circuits and communicate with other neurons. To study the role of electrical and synaptic activity on neuronal integration we have developed new tools to manipulate the biophysical properties of neurons by genetically modifying the activity of ion channels and neurotransmitter receptors.

        Genetic control of the assembly of circuits involved in vocal learning.

        Vocal learning depends on the ability of brain circuits to perceive and imitate sound sequences and use these sequences for communication. Songbirds such as canaries and zebra finches have been a favorite experimental system for the study of vocal learning in animals for decades. These animals exhibit a robust and spontaneous vocal learning behavior, and they have dedicated brain circuits, known as the song system, that participate in the learning and production of song. Zebra finches listen to the songs that their fathers produce, and imitate these sounds until they acquire a stable adult-like song. In this respect, the time course and strategy of vocal learning in zebra finches is very similar to the manner in which human infants learn to speak. These observations suggest that the zebra finch could be an ideal system where to start investigating the genetic and biological basis of vocal learning. Recently, my laboratory has succeeded in the development of a series of techniques that allow us to genetically modify the brain of songbirds. These technical advances open new opportunities for the study of the relationship between genes and learning in an animal species with a robust behavioral repertoire. We are currently generating transgenic songbirds to manipulate key genes involved in the assembly of circuits involved in vocal learning behavior.

        Figure 1: Genetic manipulation of the electrical properties of neurons.

        Newly-generated neurons (green) in the hippocampus of adult mice are rendered hyperexcitable by delivering into them a voltage-gated channel via recombinant retroviruses. Enhanced excitability increases the number of inhibitory synapses (arrows) on the genetically modified neurons (green). Bygenetically controlling the electrical properties of neurons we investigate how neuronal activity regulates the integration of cells into brain circuits, and the connections between neurons.

         

        fig test

        Figure 3: Genetically modified songbirds to investigate the molecular bases of vocal learning anc complex behavior.

        Our lab has developed several techniques to genetically manipulate the development and function of neurons during the assembly of neuronal circuits. We are using transgenic animals to investigate the rules by which neurons migrate, choose their final locations, and establish connections with each other. We are generating transgenic songbirds to investigate the genetic basis of the assembly of brain circuits involved in vocal communication.



        Rotation Projects
        Our laboratory uses tools of molecular biology, cell biology and electrophysiology to investigate the assembly of brain circuits.  Two rotation projects are available:

        1) to explore the role of neuronal activity on the migration and formation of synapses

        2) to design a transsynaptic genetic system to elucidate the wiring diagram of brain circuits.  


        Post Docs

        position 1:

        JOB DESCRIPTION:
        Postdoctoral position in electrophysiology

        We are seeking a highly motivated individual to work on a research project focused on the assembly and wiring of brain circuits. The research combines techniques in electrophysiology, molecular biology, neuroanatomy, virology, and transgenesis in rodents. Applicants with experience in electrophysiology who are motivated for developing careers as independent investigators, are especially encouraged.

        REQUIREMENTS:
        A Ph.D. in neuroscience or a related field is required and candidates should have a record of research excellence demonstrated by publication. Experience with electrophysiological recordings in vivo or in slices is required.

        CONTACT:
        carlos.lois@umassmed.edu

        position 2:

        JOB DESCRIPTION:
        Postdoctoral position in developmental neuroscience

        We are seeking a highly motivated individual to work on a research project focused on the assembly and wiring of brain circuits. The research combines techniques in electrophysiology, molecular biology, neuroanatomy, virology, and transgenesis in rodents. Applicants with experience in molecular or cell biology who are motivated for developing careers as independent investigators, are especially encouraged.

        REQUIREMENTS:
        A Ph.D. in neuroscience or a related field is required and candidates should have a record of research excellence demonstrated by publication. Expertise in molecular biology, cell biology and/or neuroscience is required.

        CONTACT:
        carlos.lois@umassmed.edu



        Two postdoctoral positions are available to study in this laboratory.  



        Bibliographic 
        selected publications
        List All   |   Timeline
        1. Sim S, Antolin S, Lin CW, Lin YX, Lois C. Increased cell-intrinsic excitability induces synaptic changes in new neurons in the adult dentate gyrus that require npas4. J Neurosci. 2013 May 1; 33(18):7928-40.
          View in: PubMed
        2. Ohtsuki G, Nishiyama M, Yoshida T, Murakami T, Histed M, Lois C, Ohki K. Similarity of Visual Selectivity among Clonally Related Neurons in Visual Cortex. Neuron. 2012 Jul 12; 75(1):65-72.
          View in: PubMed
        3. Kelsch W, Stolfi A, Lois C. Genetic Labeling of Neuronal Subsets through Enhancer Trapping in Mice. PLoS One. 2012; 7(6):e38593.
          View in: PubMed
        4. Kelsch W, Sim S, Lois C. Increasing heterogeneity in the organization of synaptic inputs of mature olfactory bulb neurons generated in newborn rats. J Comp Neurol. 2012 Apr 15; 520(6):1327-38.
          View in: PubMed
        5. Magavi S, Friedmann D, Banks G, Stolfi A, Lois C. Coincident generation of pyramidal neurons and protoplasmic astrocytes in neocortical columns. J Neurosci. 2012 Apr 4; 32(14):4762-72.
          View in: PubMed
        6. Scott BB, Gardner T, Ji N, Fee MS, Lois C. Wandering neuronal migration in the postnatal vertebrate forebrain. J Neurosci. 2012 Jan 25; 32(4):1436-46.
          View in: PubMed
        7. Lois C, Groves JO. Genetics in non-genetic model systems. Curr Opin Neurobiol. 2012 Feb; 22(1):79-85.
          View in: PubMed
        8. Scott BB, Velho TA, Sim S, Lois C. Applications of avian transgenesis. ILAR J. 2010 Oct 18; 51(4):353-61.
          View in: PubMed
        9. Lin CW, Sim S, Ainsworth A, Okada M, Kelsch W, Lois C. Genetically increased cell-intrinsic excitability enhances neuronal integration into adult brain circuits. Neuron. 2010 Jan 14; 65(1):32-9.
          View in: PubMed
        10. Kelsch W, Sim S, Lois C. Watching synaptogenesis in the adult brain. Annu Rev Neurosci. 2010; 33:131-49.
          View in: PubMed
        11. Agate RJ, Scott BB, Haripal B, Lois C, Nottebohm F. Transgenic songbirds offer an opportunity to develop a genetic model for vocal learning. Proc Natl Acad Sci U S A. 2009 Oct 20; 106(42):17963-7.
          View in: PubMed
        12. Kelsch W, Lin CW, Mosley CP, Lois C. A critical period for activity-dependent synaptic development during olfactory bulb adult neurogenesis. J Neurosci. 2009 Sep 23; 29(38):11852-8.
          View in: PubMed
        13. Magavi SS, Lois C. Transplanted neurons form both normal and ectopic projections in the adult brain. Dev Neurobiol. 2008 Dec; 68(14):1527-37.
          View in: PubMed
        14. Kelsch W, Lin CW, Lois C. Sequential development of synapses in dendritic domains during adult neurogenesis. Proc Natl Acad Sci U S A. 2008 Oct 28; 105(43):16803-8.
          View in: PubMed
        15. Chen J, Chen SC, Stern P, Scott BB, Lois C. Genetic strategy to prevent influenza virus infections in animals. J Infect Dis. 2008 Feb 15; 197 Suppl 1:S25-8.
          View in: PubMed
        16. Kelsch W, Mosley CP, Lin CW, Lois C. Distinct mammalian precursors are committed to generate neurons with defined dendritic projection patterns. PLoS Biol. 2007 Nov; 5(11):e300.
          View in: PubMed
        17. Scott BB, Lois C. Developmental origin and identity of song system neurons born during vocal learning in songbirds. J Comp Neurol. 2007 May 10; 502(2):202-14.
          View in: PubMed
        18. Rivera FJ, Couillard-Despres S, Pedre X, Ploetz S, Caioni M, Lois C, Bogdahn U, Aigner L. Mesenchymal stem cells instruct oligodendrogenic fate decision on adult neural stem cells. Stem Cells. 2006 Oct; 24(10):2209-19.
          View in: PubMed
        19. Scott BB, Lois C. Generation of transgenic birds with replication-deficient lentiviruses. Nat Protoc. 2006; 1(3):1406-11.
          View in: PubMed
        20. Scott BB, Lois C. Generation of tissue-specific transgenic birds with lentiviral vectors. Proc Natl Acad Sci U S A. 2005 Nov 8; 102(45):16443-7.
          View in: PubMed
        21. Nakagawa T, Feliu-Mojer MI, Wulf P, Lois C, Sheng M, Hoogenraad CC. Generation of lentiviral transgenic rats expressing glutamate receptor interacting protein 1 (GRIP1) in brain, spinal cord and testis. J Neurosci Methods. 2006 Apr 15; 152(1-2):1-9.
          View in: PubMed
        22. Alvarez-Dolado M, Pardal R, Garcia-Verdugo JM, Fike JR, Lee HO, Pfeffer K, Lois C, Morrison SJ, Alvarez-Buylla A. Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes. Nature. 2003 Oct 30; 425(6961):968-73.
          View in: PubMed
        23. Lois C, Hong EJ, Pease S, Brown EJ, Baltimore D. Germline transmission and tissue-specific expression of transgenes delivered by lentiviral vectors. Science. 2002 Feb 1; 295(5556):868-72.
          View in: PubMed
        24. Lois C, Refaeli Y, Qin XF, Van Parijs L. Retroviruses as tools to study the immune system. Curr Opin Immunol. 2001 Aug; 13(4):496-504.
          View in: PubMed
        25. Kirschenbaum B, Doetsch F, Lois C, Alvarez-Buylla A. Adult subventricular zone neuronal precursors continue to proliferate and migrate in the absence of the olfactory bulb. J Neurosci. 1999 Mar 15; 19(6):2171-80.
          View in: PubMed
        26. Yoon SO, Lois C, Alvirez M, Alvarez-Buylla A, Falck-Pedersen E, Chao MV. Adenovirus-mediated gene delivery into neuronal precursors of the adult mouse brain. Proc Natl Acad Sci U S A. 1996 Oct 15; 93(21):11974-9.
          View in: PubMed
        27. Lois C, GarcĂ­a-Verdugo JM, Alvarez-Buylla A. Chain migration of neuronal precursors. Science. 1996 Feb 16; 271(5251):978-81.
          View in: PubMed
        28. Alvarez-Buylla A, Lois C. Neuronal stem cells in the brain of adult vertebrates. Stem Cells. 1995 May; 13(3):263-72.
          View in: PubMed
        29. Rousselot P, Lois C, Alvarez-Buylla A. Embryonic (PSA) N-CAM reveals chains of migrating neuroblasts between the lateral ventricle and the olfactory bulb of adult mice. J Comp Neurol. 1995 Jan 2; 351(1):51-61.
          View in: PubMed
        30. Lois C, Alvarez-Buylla A. Long-distance neuronal migration in the adult mammalian brain. Science. 1994 May 20; 264(5162):1145-8.
          View in: PubMed
        31. Lois C, Alvarez-Buylla A. Proliferating subventricular zone cells in the adult mammalian forebrain can differentiate into neurons and glia. Proc Natl Acad Sci U S A. 1993 Mar 1; 90(5):2074-7.
          View in: PubMed
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