Architecture, dynamics, and resilience of brain circuits
Our laboratory investigates the mechanisms by which the coordinated activity of neurons connected to each other in circuits gives rise to brain function. To address this issue we focus on three complementary questions: (i) what is the wiring diagram of the connections that link neurons together in a circuit?, (ii) how does information flow through a neuronal circuit?, and (iii) what are the mechanisms by which the function of brain circuits remains reliable despite noise?. To investigate these questions we are developing new genetic technologies to identify neuronal connectivity, to manipulate the biophysical properties of neurons, and to record their dynamics. In addition, we use electrophysiological methods to study neuronal activity in single cells, and optical imaging methods to record the activity of large numbers of neurons in behaving animals.
Wiring diagrams of brain circuits
Understanding how information flows through brain circuits requires identifying how neurons in those circuits are connected to each other. We have designed a new genetic strategy to visualize the wiring diagram of brain circuits based on transneuronal activation of transcription. This system is allowing 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. We initially developed this tracing method in Drosophila because of its powerful genetics, and are currently applying it to visualize wiring diagrams in the mouse brain.
Generation of sequences by brain circuits
One of the fundamental characteristics of brain function is that neuronal activity occurs in a sequential manner. For example, all motor behaviors are characterized by the activation of muscles in a defined sequence. How does information flow through a neuronal circuit to generate sequences? Birdsong is an ideal system where to study the generation of sequences by brain circuits, because a song is a sequence of sounds that birds use to communicate. In addition, birds have specialized brain circuits dedicated to the production and perception of song. We are investigating the wiring diagram of these brain circuits, and how activity flows through these circuits to generate songs. To study these questions our laboratory has developed new methods that allow us to genetically modify the biophysical properties of songbird neurons, and to record the activity of large numbers of neurons in freely moving, behaving animals.
Resilience of neuronal activity in brain circuits
Brain function is remarkably reliable despite the imprecise performance of neurons, and the continuous perturbations caused by aging, disease or injury. How does the brain succeed in producing stereotypic behaviors over long periods of time despite these perturbations? We are interested in studying the cellular mechanisms by which neuronal circuits are able to "self-tune" and adapt to perturbations. We are using genetic manipulations to perturb brain circuits to ask two types of questions: (i) how do brain circuits adapt when a large percentage of their neurons are deleted or silenced?, (ii) how do brain circuits adapt when electrical noise is injected into the system?. To study these questions we are focusing on two different brain circuits: (a) the mouse olfactory system, where we can genetically perturb selective neuronal types with high precision, and (b) the song circuits of birds, because song is an extremely stereotypical behavior that can be rigorously measured
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Persistence of neuronal representations through time and damage in the hippocampus.
Gonzalez WG, Zhang H, Harutyunyan A, Lois C.
Science. 2019 Aug 23;365(6455):821-825.
In situ readout of DNA barcodes and single base edits facilitated by in vitro transcription.
Askary A, Sanchez-Guardado L, Linton JM, Chadly DM, Budde MW, Cai L, Lois C, Elowitz MB.Nat Biotechnol. 2019 38(1):66-75.
Lineage does not regulate the sensory synaptic input of projection neurons in the mouse olfactory bulb.
Sánchez-Guardado L, Lois C.
Elife. 2019 ;8:e46675.
Human Gut Microbiota from Autism Spectrum Disorder Promote Behavioral Symptoms in Mice.
Sharon G, Cruz NJ, Kang DW, Gandal MJ, Wang B, Kim YM, Zink EM, Casey CP, Taylor BC, Lane CJ, Bramer LM, Isern NG, Hoyt DW, Noecker C, Sweredoski MJ, Moradian A, Borenstein E, Jansson JK, Knight R, Metz TO, Lois C, Geschwind DH, Krajmalnik-Brown R, Mazmanian SK.
Cell. 2019 177(6):1600-1618.
In Vivo Quantitative Imaging Provides Insights into Trunk Neural Crest Migration. Li Y, Vieceli FM, Gonzalez WG, Li A, Tang W, Lois C, Bronner ME.Cell Rep. 2019 Feb 5;26(6):1489-1500.e3.
Hierarchical neural architecture underlying thirst regulation. Augustine V, Gokce SK, Lee S, Wang B, Davidson TJ, Reimann F, Gribble F, Deisseroth K, Lois C, Oka Y. Nature. 2018 Mar 8;555(7695):204-209.
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