Assembly of Brain Circuits and the Cellular Mechanisms of Behavior
Our laboratory is interested in the assembly of brain circuits and the mechanisms by which the activity of neurons in these circuits give rise to behavior. We focus on the process of neuron addition into the vertebrate brain, 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, and to identify their connectivity. To investigate how behavior arises from the activity of neurons in brain circuits, we have developed a new method to produce transgenic songbirds that allows us to manipulate key genes involved in the assembly of circuits that mediate vocal learning behavior.
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.
Assembly of brain circuits mediating vocal communication
Birds communicate through song, and their brains have specialized circuits dedicated to the production and perception of song. We are investigating how these circuits are assembled, and how their activity gives rise to song. To study these questions our laboratory has developed new methods that allow us to genetically modify the brain of songbirds. We are generating transgenic songbirds to manipulate key genes involved in the assembly of vocal communication circuits. In addition, we are investigating the cellular mechanisms that maintain stability of behavior over long periods of time.
Genetic tools to identify neuronal circuit connectivity
Understanding the computations that take place in brain circuits requires identifying how neurons in those circuits are connected. We have designed a new genetic strategy to identify the wiring diagram of brain circuits based on transneuronal activation of transcription. This system will allow us not only to identify the connections between neurons, but also to genetically modify the physiological properties of circuits of connected neurons. We anticipate that this research will provide fundamental insights to understand how neuronal activity in brain circuits gives rise to behavior.
Please click here for more information on Carlos Lois and his research.
Tracing neuronal circuits in transgenic animals by transneuronal control of transcription (TRACT). Huang TH, Niesman P, Arasu D, Lee D, De La Cruz AL, Callejas A,Hong EJ, Lois C. Elife. 2017 Dec 12;6. pii: e32027. doi: 10.7554/eLife.32027.
Methods to investigate the structure and connectivity of the nervous system. Lee D, Huang TH, De La Cruz A, Callejas A, Lois C. Fly (Austin). 2017 Jul 3;11(3):224-238.
- Liberti WA 3rd, Markowitz JE, Perkins LN, Liberti DC, Leman DP, Guitchounts G, Velho T, Kotton DN, Lois C, Gardner TJ. Unstable neurons underlie a stable learned behavior. Nat Neurosci. 2016 Dec;19(12):1665-1671. doi: 10.1038/nn.4405. View in: PubMed
- Huang TH, Velho T, Lois C.Monitoring cell-cell contacts in vivo in transgenic animals. Development. 2016 Nov 1;143(21):4073-4084. View in: PubMed
- Ravi N, Sanchez-Guardado L, Lois C, Kelsch W. Determination of the connectivity of newborn neurons in mammalian olfactory circuits. Cell Mol Life Sci. 2016 Sep 30, View in: PubMed
- Shima Y, Sugino K, Hempel CM, Shima M, Taneja P, Bullis JB, Mehta S, Lois C, Nelson SB. A Mammalian enhancer trap resource for discovering and manipulating neuronal cell types. Elife. 2016 Mar 21;5. pii: e13503. View in: PubMed
- Wu X, Zhang Y, Takle K, Bilsel O, Li Z, Lee H, Zhang Z, Li D, Fan W, Duan C, Chan EM, Lois C, Xiang Y, Han G. Dye-Sensitized Core/Active Shell Upconversion Nanoparticles for Optogenetics and Bioimaging Applications. ACS Nano. 2016 Jan 26;10(1):1060-6. View in: PubMed
- Bosch C, Martínez A, Masachs N, Teixeira CM, Fernaud I, Ulloa F, Pérez-Martínez E, Lois C, Comella JX, DeFelipe J, Merchán-Pérez A, Soriano E. FIB/SEM technology and high-throughput 3D reconstruction of dendritic spines and synapses in GFP-labeled adult-generated neurons. Front Neuroanat. 2015 May 21;9:60. View in: PubMed
- Markowitz JE, Liberti WA 3rd, Guitchounts G, Velho T, Lois C, Gardner TJ. Mesoscopic patterns of neural activity support songbird cortical sequences. PLoS Biol. 2015 Jun 3;13(6):e1002158. View in: PubMed
- Velho TA, Lois C. Generation of transgenic zebra finches with replication-deficient lentiviruses. Cold Spring Harb Protoc. 2014(12):1284-9 View in: PubMed
- Lois C, Kelsch W. Adult neurogenesis and its promise as a hope for brain repair. Front Neurosci. 2014; 8:165. View in: PubMed
- Sim S, Antolin S, Lin CW, Lin Y, 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
- 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
- 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
- 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
- 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
- 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
- Lois C, Groves JO. Genetics in non-genetic model systems. Curr Opin Neurobiol. 2012 Feb; 22(1):79-85. View in: PubMed
- 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
- Scott BB, Velho TA, Sim S, Lois C. Applications of avian transgenesis. ILAR J. 2010; 51(4):353-61. View in: PubMed
- Kelsch W, Sim S, Lois C. Watching synaptogenesis in the adult brain. Annu Rev Neurosci. 2010; 33:131-49. View in: PubMed
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- Scott BB, Lois C. Generation of transgenic birds with replication-deficient lentiviruses. Nat Protoc. 2006; 1(3):1406-11. View in: PubMed
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- Lois C, García-Verdugo JM, Alvarez-Buylla A. Chain migration of neuronal precursors. Science. 1996 Feb 16; 271(5251):978-81. View in: PubMed
- 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
- 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
- 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
- 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